Alpelisib (PIQRAY®)

Alpelisib is an orally bioavailable, small-molecule, α-specific PI3K inhibitor that selectively inhibits p110α approximately 50 times as strongly as other isoforms.  PI3K inhibition by alpelisib has been shown to induce an increase in ER transcription in breast cancer cells. The combination of alpelisib and fulvestrant demonstrated increased antitumor activity compared to either treatment alone in xenograft models derived from ER-positive, PIK3CA-mutated breast cancer cell lines

PIQRAY is indicated in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen.

Bexarotene (Targretin®), bexarotene

Bexarotene (Targretin®) is a selective retinoid X receptor (RXR) ligand.  Binding of the drug to retinoic acid receptors (RAR) is minimal, and it may be devoid of significant transactivation of RAR-responsive genes.  Activation of the RXR pathway leads to the induction of programmed cell death (apoptosis) and other cellular activities.

Bexarotene (Tagretin®) is indicated for the treatment of cutaneous manifestations of T-cell lymphoma in patients refractory to at least one prior systemic therapy.

BINIMETINIB (MEKTOVI ®)

Binimetinib (Mektovi®) is indicated to be used in combination with encorafenib for the treatment of unresectable metastatic melanoma with BRAF V600E or V600K mutation as detected by an FDA-approved test.

ENCORAFENIB (BRAFTOVI®)

BRAFTOVI is a kinase inhibitor indicated: 

Melanoma

in combination with binimetinib, for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. 

Colorectal Cancer (CRC)

in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test. This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

in combination with cetuximab, for the treatment of adult patients with metastatic CRC with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy. 

Non-Small Cell Lung Cancer (NSCLC) 

in combination with binimetinib, for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test. 

Limitations of Use BRAFTOVI is not indicated for treatment of patients with wild-type BRAF melanoma, wild-type BRAF CRC, or wild-type BRAF NSCLC. 

ERDAFITINIB (BALVERSA™)

Erdafitinib is indicated for the treatment of adults with locally advanced or metastatic urothelial carcinoma, that has susceptible fibroblast growth factor receptor, FGFR3 or FGFR2 genetic alterations, and progressed during or following at least 1 line of prior platinum-containing chemotherapy, including within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy. Select patients for the treatment with erdafitinib based on the presence of susceptible FGFR genetic alterations in tumor specimens

IVOSIDENIB (TIBSOVO®)

Ivosidenib (Tibsovo®) is an isocitrate dehydrogenase-1 (IDH1) inhibitor.

TIBSOVO is indicated for patients with a susceptible IDH1 mutation as detected by an FDA-approved test with:

• In combination with azacitidine or as monotherapy for the treatment of newly diagnosed AML in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy
• For the treatment of adult patients with relapsed or refractory AML
• For the treatment of adult patients with locally advanced or metastatic cholangiocarcinoma who have been previously treated
  

IMATINIB MESYLATE (GLEEVEC®)
Imatinib mesylate (Gleevec®) is indicated for the treatment of all of the following:

Newly diagnosed adult and pediatric patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase, Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy, Adult patients with relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), Pediatric patients with newly diagnosed Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL) in combination with chemotherapy, Adult patients with myelodysplastic/myeloproliferative diseases (MDS/MPD) associated with  platelet-derived growth factor receptor (PDGFR) gene re-arrangements, Adult patients with aggressive systemic mastocytosis (ASM) without the D816V c-Kit mutation or with c-Kit mutational status unknown, Adult patients with hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (mutational analysis or fluorescence in situ hybridization [FISH] demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFRα fusion kinase negative or unknown, Adult patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP), Patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST), Adjuvant treatment of adult patients following resection of Kit (CD117) positive GIST.

Imatinib mesylate (Gleevec®) is the first signal transduction inhibitor to be approved by the US Food and Drug Administration (FDA). These drugs are designed to prevent and stop the growth of cancer cells. Imatinib mesylate (Gleevec®) directly blocks BCR-ABL, the protein necessary for leukemia cells to survive. Imatinib mesylate (Gleevec®) also targets the activity of certain enzymes called tyrosine kinases, which play an important role within certain cancer cells. The activity of one of these tyrosine kinases, known as a stem cell factor receptor (c-Kit), is thought to drive the growth and division of most gastrointestinal stromal tumors (GISTs).

SORAFENIB (NEXAVAR®)
Sorafenib (Nexavar®) is indicated for the treatment of advanced renal cell carcinoma differentiated thyroid cancer and advanced unresectable hepatocellular carcinoma.

Sorafenib (Nexavar®) is a multikinase inhibitor that decreases tumor cell proliferation. The mechanism of action of sorafenib (Nexavar®) is not well understood, but it is believed to inhibit tumor growth in murine renal cell carcinoma and several other human tumor xenograft models. Sorafenib (Nexavar®) has also been shown to interact with multiple intracellular (CRAF, BRAF, and mutant BRAF) and cell surface kinases (KIT, FMS-like tyrosine kinase-3 [FLT-3], vascular endothelial growth factor receptors [VEGFR-3], and platelet-derived growth factor receptors [PDGFRß]), several of which are thought to be involved in angiogenesis.

LENALIDOMIDE (REVLIMID®)
Lenalidomide (Revlimid®) is indicated for the treatment of individuals who have transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes that are associated with a deletion 5q cytogenetic abnormality, with or without additional cytogenetic abnormalities. Lenalidomide (Revlimid®) in combination with dexamethasone is indicated for the treatment of multiple myeloma in individuals who have received at least one prior therapy. Lenalidomide (Revlimid®) is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib.

Lenalidomide (Revlimid®) is a thalidomide analogue. The mechanism of action of lenalidomide (Revlimid®) is not well understood. It possesses immunomodulatory and antiangiogenic properties, inhibits the secretion of proinflammatory cytokines, and increases the secretion of anti-inflammatory cytokines from peripheral blood mononuclear cells. Lenalidomide (Revlimid®) inhibits cell proliferation with varying effectiveness in some, but not all, cell lines. Of the cell lines tested, lenalidomide (Revlimid®) was effective in inhibiting the growth of Namalwa cells (a line of human B-lymphocytes with a deletion of one chromosome 5) but was much less effective in the inhibition of KG-1 cells (human myeloblastic cell lines with a deletion of one chromosome 5) and other cell lines without a chromosome 5 deletion. Lenalidomide (Revlimid®) is indicated for the treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one one of which included bortezomib.

Hematologic toxicity: Lenalidomide can cause significant neutropenia and thrombocytopenia. Eighty percent of patients with deletion 5q myelodysplastic syndromes had to have a dose delay/reduction during the major study. Thirty-four percent of patients had to have a second dose delay/reduction. Grade 3 or 4 hematologic toxicity was seen in 80% of patients enrolled in the study. Patients on therapy for deletion 5q myelodysplastic syndromes should have their complete blood cell count (CBC) monitored weekly for the first 8 weeks of therapy and at least monthly thereafter. Patients may require dose interruption and/or reduction. Patients may require use of blood product support and/or growth factors.

DASATINIB (SPRYCEL®)
Dasatinib (Sprycel®) is indicated for the treatment of adults with newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. Dasatinib (Sprycel®) is also indicated for the treatment of adult patients with chronic, accelerated. or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib. Dasatinib (Sprycel®) is also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) who have demonstrated resistance or intolerance to prior therapy. Dasatinib (Sprycel®) is also indicated for the treatment of Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.  Dasatinib (Sprycel®) is indicated for the treatment of pediatric patients 1 year of age and older with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) in combination with chemotherapy.

Dasatinib (Sprycel®) is a multityrosine kinase inhibitor that limits the activity of BCR-ABL, SRC family, c-Kit, EPHA2, and PDGFRß tyrosine kinases. This results in an inhibition of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) cell lines that overexpress BCR-ABL. Dasatinib (Sprycel®) has also been shown to be effective for individuals who have demonstrated resistance or intolerance to imatinib mesylate (Gleevec®).

SUNITINIB MALATE (SUTENT®)
Sunitinib malate (Sutent®) is indicated for the treatment of the following conditions:

• GIST after trial and failure of or intolerance to imatinib mesylate (Gleevec®)
• Advanced renal cell carcinoma (RCC)
• Progressive, well differentiated pancreatic neuroendocrine tumors in patients with unresectable locally advanced or metastatic disease
• Adjuvant treatment of adult patients at high risk of recurrent RCC following nephrectomy.     

Sunitinib malate (Sutent®) is a multikinase inhibitor that targets several receptor tyrosine kinases (RTKs), some of which are implicated in tumor growth, pathologic angiogenesis, and/or a metastatic progression of cancer. The mechanism of action of sunitinib malate (Sutent®) is not well understood. It is believed that sunitinib malate (Sutent®) inhibits platelet-derived growth factor receptors (PGFRa and PDGFRß), vascular endothelial growth factor receptors (VEGR1, VEGFR2, and VEGFR3), c-Kit, FLT3, colony-stimulating factor 1 receptor (CSF-1R), and the glial cell line-derived neutrophic factor receptor (RET). Several of these kinases are thought to be involved in angiogenesis.

ERLOTINIB (TARCEVA®)

Erlotinib (Tarceva®) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test receiving first-line, maintenance, or second or greater line treatment after progression following at least one prior chemotherapy regimen. Also indicated for pancreatic cancer as first line treatment.

Erlotinib (Tarceva®) is described as a human epidermal growth factor receptor type 1 (HER1)/EGFR tyrosine kinase inhibitor. Its mechanism of antitumor action is not fully understood. It inhibits the phosphorylation of tyrosine kinase associated with EGFR. The specificity of tyrosine kinase receptor inhibition has not been defined. EGFR is expressed on the cell surfaces of normal cells and cancer cells. Two multicenter, placebo-controlled, randomized Phase III trials were conducted in first-line individuals who had locally advanced or metastatic non-small cell lung cancer (NSCLC), and the results showed no clinical benefit with the concurrent administration of erlotinib (Tarceva®). Erlotinib (Tarceva®) with platinum-based chemotherapy (carboplatin and paclitaxel or gemcitabine and cisplatin) is not recommended for use in this setting.

APALUTAMIDE (ERLEADA™)
Apalutamide (ErleadaTM) is an androgen receptor inhibitor indicated for the treatment of patients with metastatic castration-sensitive prostate cancer and non-metastatic castration-resistant prostate cancer.

THALIDOMIDE (Thalomid®)

Thalidomide (Thalomid®) is indicated:

1. In combination with dexamethasone, for the treatment of patients with newly diagnosed multiple myeloma (MM)

2. For the acute treatment of cutaneous manifestations of severe erythema nodosum leprosum (ENL); not indicated as monotherapy for such ENL treatment in the presence of moderate to severe neuritis

3. As maintenance therapy for prevention and suppression of the cutaneous manifestations of ENL relapse manifestations of ENL relapse

The mechanism of action of thalidomide (Thalomid®) is not fully understood. Thalidomide possesses immunomodulatory, anti-inflammatory and antiangiogenic properties. Available data from in vitro studies and clinical trials suggest that the immunologic effects of this compound can vary substantially under different conditions, but may be related to suppression of excessive tumor necrosis factor-alpha (TNF-α) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. For example, administration of thalidomide has been reported to decrease circulating levels of TNF-α in patients with erythema nodosum leprosum (ENL); however, it has also been shown to increase plasma TNF-α levels in HIV-seropositive patients. Other anti-inflammatory and immunomodulatory properties of thalidomide may include suppression of macrophage involvement in prostaglandin synthesis, and modulation of interleukin-10 and interleukin-12 production by peripheral blood mononuclear cells. Thalidomide treatment of multiple myeloma patients is accompanied by an increase in the number of circulating natural killer cells, and an increase in plasma levels of interleukin-2 and interferon-gamma (T cell-derived cytokines associated with cytotoxic activity). Thalidomide was found to inhibit angiogenesis in a human umbilical artery explant model in vitro. The cellular processes of angiogenesis inhibited by thalidomide may include the proliferation of endothelial cells.

VORINOSTAT (ZOLINZA®)
Vorinostat (Zolinza®) is a histone deacetylase (HDAC) inhibitor indicated for the treatment of individuals with cutaneous T-cell lymphoma (CTCL) who have progressive, persistent, or recurrent disease on or following two systemic therapies.

Vorinostat (Zolinza®) inhibits the enzymatic activity of histone deacetylases (HDACs) Class I (i.e., HDAC1, HDAC2, and HDAC3) and Class II (ie, HDAC6) at nanomolar concentrations (inhibitory concentration [IC50] less than 86 nM). In some cancer cells, there is an overexpression of HDACs or an aberrant recruitment of HDACs to oncogenic transcription factors causing hypoacetylation of core nucleosomal histones. Hypoacetylation of histones is associated with a condensed chromatin structure and repression of gene transcription. Inhibition of HDAC activity allows for the accumulation of acetyl groups on the histone lysine residues, resulting in an open chromatin structure and transcription activation. In vitro, vorinostat (Zolinza®) causes the accumulation of acetylated histones and induces cell cycle arrest and/or apoptosis of some transformed cells. The mechanism of the antineoplastic effect of vorinostat (Zolinza®) is not fully understood.

LAPATINIB (TYKERB®)
Lapatinib (Tykerb®) is indicated for use in combination with capecitabine (Xeloda®) for the treatment of individuals with advanced or metastatic breast cancer whose tumors overexpress the HER2 protein and who have received prior therapy with an anthracycline, a taxane, and trastuzumab (Herceptin®). It is also indicated for use in combination with letrozole for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer that overexpresses the HER2 receptor for whom hormonal therapy is indicated.

Limitation of Use: Patients should have disease progression on trastuzumab prior to initiation of treatment with TYKERB® in combination with capecitabine.

Lapatinib (Tykerb®) is an inhibitor of the EGFR (Epidermal growth factor receptor; also called HER1 or ErbB1) and HER2 receptor tyrosine kinases, thereby inhibiting ErbB-driven tumor cell growth.

NILOTINIB (TASIGNA®)

Nilotinib (Tasigna®) is indicated for the following:

Adult and pediatric patients greater than or equal to 1 year of age with newly diagnosed Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase..

Adult patients with chronic phase (CP) and accelerated phase (AP) Ph+ CML resistant to or intolerant to prior therapy that included imatinib.

Pediatric patients greater than or equal to 1 year of age with Ph+ CML-CP and CML-AP resistant or intolerant to prior tyrosine-kinase inhibitor (TKI) therapy.

Nilotinib (Tasigna®) is a selective tyrosine kinase inhibitor which binds to and stabilizes the inactive conformation of the kinase domain of the Abl protein. Bcr-Abl is the oncogenic tyrosine kinase expressed by Philadelphia chromosome-positive (Ph+) stem cells, directly involved in the pathogenesis of CML. Nilotinib inhibits the autophosphorylation of Bcr-Abl, PDGFR, and c-Kit, thereby reducing the tumor size.

TOPOTECAN CAPSULES (HYCAMTIN®)
Topotecan capsule (Hycamtin®)is indicated for the treatment of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.

Topotecan capsule (Hycamtin®) is a semi-synthetic derivative of camptothecin and is an anti-tumor drug. The anti-tumor activity of topotecan involves the inhibition of topoisomerase-I, an enzyme intimately involved in DNA replication as it relieves the torsional strain introduced ahead of the moving replication fork. Topotecan inhibits topoisomerase-I by stabilizing the covalent complex of enzyme and strand-cleaved DNA, which is an intermediate of the catalytic mechanism. The cellular sequel of inhibition of topoisomerase-I by topotecan is the induction of protein-associated DNA single-strand breaks. The cytotoxicity of topotecan is thought to be due to double strand DNA damage produced during DNA synthesis, when replication enzymes interact with the ternary complex formed by topotecan, topoisomerase I, and DNA. Mammalian cells cannot efficiently repair these double strand breaks.

TEMOZOLOMIDE (TEMODAR®)
Temozolomide (Temodar®) is indicated for the treatment of adult patients with refractory anaplastic astrocytoma (ie, patients who have experienced disease progression on a drug regimen containing a nitrosourea and procarbazine) and for the treatment of adults with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as maintenance treatment.

Temozolomide (Temodar®), an imidazotetrazine derivative, is not directly active but undergoes rapid nonenzymatic conversion at physiologic pH to the reactive compound 5-(3-methyltriazen-1-yl),imidazole-4-carboxamide (MTIC). The cytotoxicity of MTIC is thought to be caused primarily by alkylation of DNA. Alkylation (methylation) occurs mainly at the O6 and N7 positions of guanine.

EVEROLIMUS (AFINITOR®, TORPENZ)
Everolimus (Afinitor®, Torpenz) is indicated for the treatment of advanced renal cell carcinoma (RCC), in patients who failed treatment with sunitinib (Sutent®) or sorafenib (Nexavar®). Everolimus (Afinitor®, Torpenz) is also indicated for the treatment of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TS). Afinitor®/Torpenz is also indicated for the treatment of progressive neuroendocrine tumors of pancreatic origin (PNET) in patients with unresectable, locally advanced or metastatic disease. Afinitor®/Torpenz is also indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane after failure of treatment with letrozole or anastrozole.

Everolimus (Afinitor®/Torpenz) is a kinase inhibitor, a derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target of Rapamycin (mTOR), a key regulatory kinase. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production.

FLUDARABINE PHOSPHATE (Oforta™)

Fludarabine Phosphate (Oforta™) is indicated for a diagnosis of B-cell chronic lymphocytic leukemia (CLL) whose disease has not responded to or has progressed during or after treatment with at least one standard alkylating-agent containing regimen.

Fludarabine Phosphate (Oforta™) is a synthetic purine nucleotide antimetabolite agent. Upon administration, fludarabine phosphate is rapidly dephosphorylated in the plasma to 2F-ara-A, which then enters into the cell. Intracellularly, 2F-ara-A is converted to the 5'-triphosphate, 2-fluoro-ara-ATP (2F-ara-ATP). 2F-ara-ATP competes with deoxyadenosine triphosphate for incorporation into DNA. Once incorporated into DNA, 2F-ara-ATP functions as a DNA chain terminator, inhibits DNA polymerase alpha, gamma, and delta, and inhibits ribonucleoside diphosphate reductase. 2F-ara-A also inhibits DNA primase and DNA ligase I. The mechanism of action of this antimetabolite is not completely characterized and may be multi-faceted.

PAZOPANIB (Votrient™)

Pazopanib (Votrient™) is indicated for the treatment of advanced renal cell carcinoma and advanced soft tissue sarcoma who have received prior chemotherapy.

Pazopanib (Votrient™) is a multi-tyrosine kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR)-alpha and -beta, fibroblast growth factor receptor (FGFR)-1 and -3, cytokine receptor (Kit), interleukin-2 receptor inducible T-cell kinase (Itk), leukocyte-specific protein tyrosine kinase (Lck), and transmembrane glycoprotein receptor tyrosine kinase (c-Fms). In vitro, pazopanib inhibited ligand-induced autophosphorylation of VEGFR-2, Kit and PDGFR-beta receptors. In vivo, pazopanib inhibited VEGF-induced VEGFR-2 phosphorylation in mouse lungs, angiogenesis in a mouse model, and the growth of some human tumor xenografts in mice.

VANDETANIB (Caprelsa®)

Vandetanib (Caprelsa®) is indicated for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.

Vandetanib (Caprelsa®) is a kinase inhibitor. Studies have shown that vandetanib inhibits the activity of tyrosine kinases including members of the epidermal growth factor receptor (EGFR) family. Vandetanib inhibits endothelial cell migration, proliferation, survival and new blood vessel formation in in vitro models of angiogenesis. Vandetanib inhibits EGFR-dependent cell survival in vitro. In addition, vandetanib inhibits epidermal growth factor (EGF)-stimulated receptor tyrosine kinase phosphorylation in tumor cells and endothelial cells and VEGF-stimulated tyrosine kinase phosphorylation in endothelial cells.

ABIRATERONE (Zytiga®)

Abiraterone (Zytiga®) in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer who have received prior chemotherapy containing docetaxel.

Abiraterone acetate (Zytiga®) is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Zytiga® decreased serum testosterone and other androgens in patients in the placebo-controlled phase 3 clinical trial.

VEMURAFENIB (ZELBORAF®)

Vemurafenib (Zelboraf®) is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test and for the treatment of patients with Erdheim-Chester Disease with BRAF V600 mutation.

Vemurafenib (Zelboraf®) is a low molecular weight, orally available, inhibitor of some mutated forms of BRAF serine-threonine kinase, including BRAFV600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5 and FGR at similar concentrations. Some mutations in the BRAF gene including V600E result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation. Vemurafenib has anti-tumor effects in cellular and animal models of melanomas with mutated BRAFV600E 

CRIZOTINIB (XALKORI®)

Crizotinib (Xalkori®) is a kinase inhibitor indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test. It is also indicated for pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive and adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive..

Limitations of Use: The safety and efficacy of XALKORI have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.

Crizotinib (Xalkori®) is an inhibitor of receptor tyrosine kinases including ALK, Hepatocyte Growth Factor Receptor (HGFR, c-Met), and Recepteur d'Origine Nantais (RON). Translocations can affect the ALK gene resulting in the expression of oncogenic fusion proteins. The formation of ALK fusion proteins results in activation and dysregulation of the gene's expression and signaling which can contribute to increased cell proliferation and survival in tumors expressing these proteins. Crizotinib demonstrated concentration-dependent inhibition of ALK and c-Met phosphorylation in cell-based assays using tumor cell lines and demonstrated antitumor activity in mice bearing tumor xenografts that expressed EML4- or NPM-ALK fusion proteins or c-Met.

RUXOLITINIB (JAKAFI®)

Ruxolitinib (Jakafi®) is indicated for treatment of patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Ruxolitinib is also indicated for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.

Ruxolitinib (Jakafi®), a kinase inhibitor, inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2 which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression.

AXITINIB (Inlyta®)

Axitinib (Inlyta®) is indicated for the treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.

Axitinib (Inlyta®) has been shown to inhibit receptor tyrosine kinases including vascular endothelial growth factor receptors (VEGFR)-1, VEGFR-2, and VEGFR-3 at therapeutic plasma concentrations. These receptors are implicated in pathologic angiogenesis, tumor growth, and cancer progression. VEGF-mediated endothelial cell proliferation and survival were inhibited by axitinib in vitro and in mouse models. Axitinib was shown to inhibit tumor growth and phosphorylation of VEGFR-2 in tumor xenograft mouse models.

VISMODEGIB (Erivedge®)

Vismodegib (Erivedge®) is indicated for the treatment of adults with metastatic basal cell carcinoma, or with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation.

Vismodegib (Erivedge®) is an inhibitor of the Hedgehog pathway. Vismodegib binds to and inhibits smoothened, a transmembrane protein involved in Hedgehog signal transduction.

ENZALUTAMIDE (Xtandi®)

Enzalutamide (Xtandi®) is indicated for the treatment of patients with castration-resistant prostate cancer and metastatic castration-sensitive prostate cancer (mCSPC).

Enzalutamide (Xtandi®) is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA. A major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to enzalutamide. Enzalutamide decreased proliferation and induced cell death of prostate cancer cells in vitro, and decreased tumor volume in a mouse prostate cancer xenograft model.

BOSUTINIB (Bosulif®)
BOSULIF is a kinase inhibitor indicated for the treatment of

• adult and pediatric patients 1 year of age and older with chronic phase Ph+ chronic myelogenous leukemia (CML), newly-diagnosed or resistant or intolerant to prior therapy. 
• adult patients with accelerated, or blast phase Ph+ CML with resistance or intolerance to prior therapy.

REGORAFENIB (Stivarga®)

Regorafenib (Stivarga®) is indicated for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild type, an anti-EGFR therapy. Regorafenib is also indicated for the treatment of patients with locally advanced, unresectable or metastatic gastrointestinal stromal tumor (GIST) who have been previously treated with imatinib mesylate and sunitinib malate. Regorafenib is also indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.

Regorafenib (Stivarga®) is a small molecule inhibitor of multiple membrane-bound and intracellular kinases involved in normal cellular functions and in pathologic processes such as oncogenesis, tumor angiogenesis, and maintenance of the tumor microenvironment.

PONATINIB (Iclusig®)

Ponatinib (Iclusig®) is indicated for the treatment of adult patients with accelerated phase, or blast phase chronic myeloid leukemia (CML) or Ph+ ALL for whom no other tyrosine kinase inhibitor (TKI) therapy is indicated, and chronic phase CML with resistance or intolerance to at least two prior kinase inhibitors.  Ponatinib is also indicated for the treatment of adult patients with T315I-positive CML (chronic phase, accelerated phase, or blast phase) or T315I-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL).

Ponatinib (Iclusig®) inhibits the in vitro tyrosine kinase activity of Abelson murine leukemia (ABL) and T315I mutant ABL with half maximal inhibitory concentrations (IC50) of 0.4 and 2 nM, respectively. Ponatinib also inhibits the in vitro activity of additional kinases with IC50 concentrations between 0.1 and 20 nM, including members of the VEGFR, PDGFR, FGFR, EPH receptors and SRC families of kinases, and KIT, RET, TIE2, and FLT3. Ponatinib inhibits the in vitro viability of cells expressing native or mutant breakpoint cluster region–ABL, including T315I.

CABOZANTINIB (Cabometyx®)

CABOMETYX is a kinase inhibitor indicated for the treatment of 

• patients with advanced renal cell carcinoma (RCC). 
• patients with advanced renal cell carcinoma, as a first-line treatment in combination with nivolumab. 
• patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. 
• adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior VEGFR-targeted therapy and who are radioactive iodine-refractory or ineligible.
• adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated pancreatic neuroendocrine tumors (pNET). 
• adult and pediatric patients 12 years of age and older with previously treated, unresectable, locally advanced or metastatic, well-differentiated extra-pancreatic neuroendocrine tumors (epNET). 

POMALIDOMIDE (Pomalyst®)

Pomalidomide (Pomalyst®) is indicated for the treatment of adult patients:

In combination with dexamethasone for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

With AIDS-related Kaposi sarcoma (KS) after failure of highly active antiretroviral therapy (HAART) or in patients with KS who are HIVnegative. This indication is approved under accelerated approval based on overall response rate.  Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s)

Pomalidomise (Pomalyst)®, an analogue of thalidomide, is an immunomodulatory agent with antineoplastic activity. In in vitro cellular assays, pomalidomide inhibited proliferation and induced apoptosis of hematopoietic tumor cells. Additionally, pomalidomide inhibited the proliferation of lenalidomide-resistant multiple myeloma cell lines and synergized with dexamethasone in both lenalidomide-sensitive and lenalidomide-resistant cell lines to induce tumor cell apoptosis.

DABRAFENIB (Tafinlar®)

TAFINLAR is a kinase inhibitor indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test.

TAFINLAR is indicated, in combination with trametinib, for:

• the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.
• the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.
• the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.
• the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options.
• the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DoR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
• the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.

Limitations of Use: TAFINLAR is not indicated for treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition. TAFINLAR is not indicated for treatment of patients with wildtype BRAF solid tumors.

TRAMETINIB (Mekinist®)

MEKINIST is a kinase inhibitor indicated as a single agent for the treatment of BRAF-inhibitor treatment-naïve patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA[1]approved test.

MEKINIST is indicated, in combination with dabrafenib, for:

• the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test.
• the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.  
• the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test.
• the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options.
• the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
• the treatment of pediatric patients 1 year of age and older with low-grade glioma (LGG) with a BRAF V600E mutation who require systemic therapy.

Limitations of Use: MEKINIST is not indicated for treatment of patients with colorectal cancer because of known intrinsic resistance to BRAF inhibition.

Trametinib (Mekinist®), a kinase inhibitor, is a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. BRAFV600E mutations result in constitutive activation of the BRAF pathway, which includes MEK1 and MEK2. Trametinib inhibits BRAFV600 mutation-positive melanoma cell growth in vitro and in vivo.

AFATINIB (Gilotrif®)

Afatinib (Gilotrif®) is indicated as a first-line treatment of metastatic non–small cell lung cancer in patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by a Food and Drug Administration–approved test. Afatinib is also indicated for the treatment of patients with metastatic, squamous NSCLC progressing after platinum-based chemotherapy.

Afatinib (Gilotrif®) a tyrosine kinase inhibitor, covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4), and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling.

IBRUTINIB (Imbruvica®)
IMBRUVICA is a kinase inhibitor indicated for the treatment of:

• Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL).
• Adult patients with chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) with 17p deletion
• Adult patients with Waldenström's macroglobulinemia (WM)
• Adult and pediatric patients age 1 year and older with chronic graft versus host disease (cGVHD) after failure of one or more lines of systemic therapy
  

Ibrutinib (Imbruvica®) is a potent and irreversible inhibitor of Bruton tyrosine kinase (BTK), an integral component of the B-cell receptor (BCR) and cytokine receptor pathways. Constitutive activation of B-cell receptor signaling is important for survival of malignant B-cells; BTK inhibition results in decreased malignant B-cell proliferation and survival.

CERTINIB (Zykadia®)

Ceritinib (Zykadia®) is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)–positive metastatic nonsmall cell lung cancer (NSCLC) who has progressed on or are intolerant to crizotinib

Certinib (Zykadia®) is a potent inhibitor of anaplastic lymphoma kinase (ALK), a tyrosine kinase involved in the pathogenesis of nonsmall cell lung cancer. ALK gene abnormalities due to mutations or translocations may result in expression of oncogenic fusion proteins (e.g., ALK fusion protein) which alter signaling and expression and result in increased cellular proliferation and survival in tumors which express these fusion proteins. ALK inhibition reduces proliferation of cells expressing the genetic alteration. Ceritinib also inhibits insulinlike growth factor 1 receptor (IGF-1R), insulin receptor (InsR), and ROS1. Ceritinib has demonstrated activity in crizotinib-resistant tumors in NSCLC xenograft models.

IDELALISIB (Zydelig®)
Zydelig is a kinase inhibitor indicated for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients for whom rituximab alone would be considered appropriate therapy due to other co-morbidities.

Limitations of use:

Zydelig is not indicated and is not recommended for first-line treatment of any patient, including patients with CLL, small lymphocytic lymphoma (SLL), follicular lymphoma (FL), and other indolent nonHodgkin lymphomas.

Zydelig is not indicated and is not recommended in combination with bendamustine and rituximab, or in combination with rituximab for the treatment of patients with FL, SLL, and other indolent non-Hodgkin lymphomas.

Idelalisib (Zydelig®) is an inhibitor of PI3Kδ kinase, which is expressed in normal and malignant B-cells. Idelalisib induced apoptosis and inhibited proliferation in cell lines derived from malignant B-cells and in primary tumor cells. Idelalisib inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Treatment of lymphoma cells with idelalisib resulted in inhibition of chemotaxis and adhesion, and reduced cell viability. It indicated for chronic lymphocytic leukemia, follicular B-cell non-hodgkin lymphoma, and small lymphocytic lymphoma.

OLAPARIB (Lynparza®)
Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated:

Ovarian cancer

• for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.
• in combination with bevacizumab for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either:
• a deleterious or suspected deleterious BRCA mutation, and/or
• genomic instability.
• Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.
• for the maintenance treatment of adult patients with deleterious or suspected deleterious germline or somatic BRCA-mutated recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer, who are in complete or partial response to platinum-based chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.
  

Breast cancer

• for the adjuvant treatment of adult patients with deleterious or suspected deleterious gBRCAm human epidermal growth factor receptor 2 (HER2)-negative high risk early breast cancer who have been treated with neoadjuvant or adjuvant chemotherapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.
• for the treatment of adult patients with deleterious or suspected deleterious gBRCAm, HER2-negative metastatic breast cancer who have been treated with chemotherapy in the neoadjuvant, adjuvant or metastatic setting. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior endocrine therapy or be considered inappropriate for endocrine therapy. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.

Pancreatic cancer

• for the maintenance treatment of adult patients with deleterious or suspected deleterious gBRCAm metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.
  

Prostate cancer

• for the treatment of adult patients with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC) who have progressed following prior treatment with enzalutamide or abiraterone. Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza. (1.7, 2.1)
• in combination with abiraterone and prednisone or prednisolone for the treatment of adult patients with deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC). Select patients for therapy based on an FDA-approved companion diagnostic for Lynparza.
  

PALBOCICLIB (Ibrance®)

Palbociclib (Ibrance®) is indicated for the treatment of hormone receptor (HR)-positive, human epithelial growth factor receptor (HER2)-negative advanced or metastatic breast cancer in combination with: an aromatase inhibitor as initial endocrine based therapy; or in combination with fulvestrant in patients with disease progression following endocrine therapy.

Palbociclib (Ibrance®) inhibits cyclin-dependent kinase (CDK) 4 and 6.  In vitro, palbociclib reduced cellular proliferation of ER-positive breast cancer cell lines by blocking progression of the cell from G1 into S phase of the cell cycle.

LENVATINIB (Lenvima®)

Lenvatinib (Lenvima®) is indicated for:

For the treatment of patients with locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid cancer (DTC)

In combination with pembrolizumab, for the first line treatment of adult patients with advanced renal cell carcinoma (RCC).

In combination with everolimus, for the treatment of adult patients with advanced renal cell carcinoma (RCC) following one prior antiangiogenic therapy.

For the first-line treatment of patients with unresectable hepatocellular carcinoma (HCC).

In combination with pembrolizumab, for the treatment of patients with advanced endometrial carcinoma (EC) that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation

Lenvatinib (Lenvima®) is a receptor tyrosine kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VGEFR3 (FLT4).  Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.

TRIFLURIDINE/TIPIRACIL (Lonsurf®)

LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of adult patients with:

• metastatic colorectal cancer as a single agent or in combination with bevacizumab who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

• metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy 

Trifluridine/tipiracil (Lonsurf®) is a new orally administered antineoplastic combination of trifluridine, a thymidine-based nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor.

SONIDEGIB (Odomzo®)

Sonidegib (Odomzo®) the second drug in the class of Hh pathway inhibitors, was approved for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

ALECTINIB (Alecensa®)

Alectinib (Alecensa®) is a kinase inhibitor indicated for the treatment of patients with ALK-positive, metastatic NSCLC who have progressed on or are intolerant to crizotinib.  This indication is approved under accelerated approval based on tumor response rate and duration of response.

COBIMETINIB (Cotellic™)

Cobimetinib (Cotellic) is a MEK inhibitor approved to be used in combination with vemurafenib (Zelboraf) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. It is also indicated as a single agent for the treatment of adult patients with histiocytic neoplasms.

IXAZOMIB (Ninlaro®)

Ixazomib (Ninlaro®) is the first oral proteasome inhibitor approved by the FDA.  Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least 1 prior line of therapy.

OSIMERTINIB (Tagrisso™)

Osimertinib (Tagrisso™) is an irreversible third-generation TKI, indicated for:

• adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. 
• the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test.
• the first-line treatment of adult patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. 
• in combination with pemetrexed and platinum-based chemotherapy, the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. 
• the treatment of adult patients with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR TKI therapy.

VENTOCLAX (Venclexta™)

Ventoclax (Venclexta™) is a BCL-2 inhibitor indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma. It is also indicated for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy when used in combination with azacitidine, or decitabine, or low-dose cytarabine (LDAC)

RUCABARIB (Rubraca™)

Rucaparib is an inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair. In vitro studies have shown that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cancer cell death. Increased rucaparib-induced cytotoxicity and anti-tumor activity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes. Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA. 

RUBRACA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated: 

Ovarian cancer - for the maintenance treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. 

Prostate cancer - for the treatment of adult patients with a deleterious BRCA mutation (germline and/or somatic)-associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor-directed therapy. Select patients for therapy based on an FDA-approved companion diagnostic for RUBRACA. 

RIBOCICLIB (Kisqali®)

KISQALI is a kinase inhibitor indicated: 

• in combination with an aromatase inhibitor for the adjuvant treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative stage II and III early breast cancer at high risk of recurrence. 
• for the treatment of adults with HR-positive, HER2-negative advanced or metastatic breast cancer in combination with: o an aromatase inhibitor as initial endocrine-based therapy; or o fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy. 

NIRAPARIB (Zejula™)

ZEJULA is indicated for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with homologous recombination deficiency (HRD)-positive status defined by either: 

• a deleterious or suspected deleterious BRCA mutation, and/or 
• genomic instability

BRIGATINIB (Alunbrig™)

Brigatinib (Alunbrig™) is a kinase inhibitor indicated for the treatment of ALK-positive metastatic non-small cell lung cancer (NSCLC) who have progressed or are intolerant to crizotinib. The indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. This drug works by inhibiting autophosphorylation of ALK and ALK-mediated phosphorylation of downstream signaling proteins. This helps to inhibit the in vitro viability of cells expressing certain ALK and mutant ALK forms.

NERATINIB (Nerlynx™)

Neratinib (Nerlynx™) is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy. This drug works by reducing EGFR and HER2 autophosphorylation and downstream signaling pathways. It is also indicated in combination with capecitabine, for the treatment of adult patients with advanced or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 based regimens in the metastatic setting.

MIDOSTAURIN (Rydapt™)

Midostaurin (Rydapt™) is a kinase inhibitor indicated for the treatment of adult patients with the following conditions:

(1): newly diagnosed acute myeloid leukemia (AML) that is FLT3-mutation positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation

(2) aggressive systemic mastocytosis (ASM) or systemic mastocytosis with associated hematological neoplasm (SM-AHN)

(3) mast cell leukemia

ENASIDENIB (Idhifa®)

Enasidenib (Idhifa®) is an isocitrate dehydrogenase-2 inhibitor indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.

Enasidenib is a small molecule inhibitor of the isocitrate dehydrogenase 2 (IDH2) enzyme. Enasidenib targets the mutant IDH2 variants R140Q, R172S, and R172K at approximately 40-fold lower concentrations than the wild-type enzyme in vitro. Inhibition of the mutant IDH2 enzyme by enasidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH2 mutated AML. In blood samples form patients with AML with mutated IDH2, enasidenib decreased 2-HG levels, reduced blast counts and increased percentages of mature myeloid cells.

ABEMACICLIB (Verzenio®)

Abemaciclib (Verzenio®) is a kinase inhibitor indicated:

in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence

in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer

in combination with fulvestrant for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy.

As monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting.

Abemaciclib is an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6). These kinases are activated upon binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation. In vitro, continuous exposure to abemaciclib inhibited Rb phosphorylation and blocked progression from G1 into S phase of the cell cycle, resulting in senescence and apoptosis. In breast cancer xenograft models, abemaciclib dosed daily without interruption as a single agent or in combination with antiestrogens resulted in reduction of tumor size.

Acalabrutinib (Calquence ®)

CALQUENCE is a kinase inhibitor indicated:

• In combination with bendamustine and rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT). 
• For the treatment of adult patients with MCL who have received at least one prior therapy. 
• For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). 

Duvelisib (Copiktra™)

Duvelisib (Copiktra™) is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after two prior therapies. Duvelisib is an inhibitor of PI3K with inhibitory activity predominantly against PI3K-δ and PI3K-γ isoforms expressed in normal and malignant B-cells. Duvelisib induced growth inhibition and reduced viability in cell lines derived from malignant B-cells and in primary CLL tumor cells. Duvelisib inhibits several key cell-signaling pathways, including B-cell receptor signaling and CXCR12-mediated chemotaxis of malignant B-cells. Additionally, duvelisib inhibits CXCL12-induced T cell migration and M-CSF and IL-4 driven M2 polarization of macrophages.

Dacomitinib (Vizimpro®)

Dacomitinib (Vizimpro®) is a kinase inhibitor indicated for the first line treatment of individuals with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution mutations as detected by an FDA approved test. Dacomitinib is an irreversible inhibitor of the kinase activity of the human EGFR family (EGFR/HER1, HER2, and HER4) and certain EGFR activating mutations (exon 19 deletion or the exon 21 L858R substitution mutation). In vitro dacomitinib also inhibited the activity of DDR1, EPHA6, LCK, DDR2, and MNK1 at clinically relevant concentrations.

Talazoparib (Talzenna®)

TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for:

Breast Cancer

• As a single agent, for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved companion diagnostic for TALZENNA.

HRR Gene-mutated mCRPC

• In combination with enzalutamide for the treatment of adult patients with HRR gene-mutated metastatic castration-resistant prostate cancer (mCRPC).
  

Lorlatinib (Lobrena®)

Lorlatinib (Lobrena®) is a kinase inhibitor with in vitro activity against ALK and ROS1 as well as TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of ALK enzyme, including some mutations detected in tumors at the times of disease progression on crizotinib and other ALK inhibitors. Lorlatinib (Lorbrena®) is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test.

Glasdegib (Daurismo™)

Glasdegib (Daurismo™) is an inhibitor of the Hedgehog pathway. Glasdegib binds to and inhibits Smoothened, a transmembrane protein involved in Hedgehog signal transduction. Glasdegib (Daurismo™) is indicated, in combination with low-dose cytarabine, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adult patients 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy. 

Larotrectinib (Vitrakvi®)

Larotrectinib (Vitrakvi®) is an inhibitor of the tropomyosin receptor kinases (TRK), TRKA, TRKB, and TRKC. In in vitro and in vivo tumor models, larotrectinib demonstrated anti-tumor activity in cells with constitutive activation of TRK proteins resulting from gene fusions, deletion of a protein regulatory domain, or in cells with TRK protein overexpression. Larotrectinib (Vitrakvi®) is indicated for the treatment of adult and pediatric patients with solid tumors that have neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to result in severe morbidity and have no satisfactory alternative treatments or that have progressed following treatment.  

Gilteritinib (Xospata®)

Gilteritinib (Xospata®) is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD. Gilteritinib (Xospata®) is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.

Selinexor (Xpovio™)

Selinexor is a nuclear export inhibitor.  Selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and messenger ribonucleic acids (mRNAs) of oncogenic proteins by blocking exportin 1 (XPO1). This inhibition leads to accumulation of TSPs in the nucleus, reductions in several oncoproteins, cell cycle arrest, and apoptosis of cancer cells.

Selinexor is indicated:

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

For the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

DAROLUTAMIDE (NUBEQA®)

NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with: 

• non-metastatic castration-resistant prostate cancer (nmCRPC). 
• metastatic castration-sensitive prostate cancer (mCSPC).
• metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel

PEXIDARTINIB (TURALIO™)

Pexidartinib (Turalio™) is a small molecule tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD). Overexpression of CSF1R ligand promotes cell proliferation and accumulation in the synovium; pexidartinib inhibits proliferation of CSF1R-dependent cell lines. In vitro, pexidartinib also inhibits ligand-induced autophosphorylation of CSF1R.  Pexidartinib is indicated for the treatment of adults with symptomatic tenosynovial giant cell tumor associated with severe morbidity or functional limitations and not amenable to improvement with surgery

ENTRECTINIB (ROZLYTREK™)

Entrectinib (Rozlytrek™) is an inhibitor of the tropomyosin receptor tyrosine kinases (TRK) TRKA, TRKB, and TRKC (encoded by the neurotrophic tyrosine receptor kinase [NTRK] genes NTRK1, NTRK2, and NTRK3, respectively), proto-oncogene tyrosine-protein kinase ROS1 (ROS1), and anaplastic lymphoma kinase (ALK). Entrectinib also inhibits JAK2 and TNK2.  Entrectinib inhibits cancer cell lines derived from multiple tumor types harboring NTRK, ROS1, and ALK fusion genes thus inhibiting tumorigenic potential through hyperactivation of downstream signaling pathways and uncontrolled cell proliferation caused by fusion proteins. 

Entrectinib is indicated for the treatment of:

Adult patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test.

Adult and pediatric patients 12 years of age and older with solid tumors that:

have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion as detected by an FDA-approved test without a known acquired resistance mutation,

are metastatic or where surgical resection is likely to result in severe morbidity, and

have progressed following treatment or have no satisfactory alternative therapy

FEDRATINIB (INREBIC®)

Fedratinib (Inrebic®) is a kinase inhibitor with activity against wild type and mutationally activated Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). Fedratinib is a JAK2-selective inhibitor with higher inhibitory activity for JAK2 over JAK1, JAK3 and TYK2. In cell models expressing mutationally active JAK2V617F or FLT3ITD, fedratinib reduced phosphorylation of signal transducer and activator of transcription (STAT3/5) proteins, inhibited cell proliferation, and induced apoptotic cell death.  Fedratinib is indicated for the treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF)

AVAPRITINIB (AVYAKIT™)
AYVAKIT is a kinase inhibitor indicated for:

Gastrointestinal Stromal Tumor (GIST)

• the treatment of adults with unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.
  

Advanced Systemic Mastocytosis (AdvSM)

• the treatment of adult patients with AdvSM. AdvSM includes patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SMAHN), and mast cell leukemia (MCL).
• Limitations of Use: AYVAKIT is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 X 109/L
  

Indolent Systemic Mastocytosis (ISM)

• the treatment of adult patients with ISM.
• Limitations of Use: AYVAKIT is not recommended for the treatment of patients with ISM with platelet counts of less than 50 X 109/L
  

ZANUBRUTINIB (BRUKINSA™)

Zanubrutinib is a small-molecule inhibitor of BTK. Zanubrutinib forms a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK activity. BTK is a signaling molecule of the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. In nonclinical studies, zanubrutinib inhibited malignant B-cell proliferation and reduced tumor growth. BRUKINSA is indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy, Waldenström's macroglobulinemia (WM), Relapsed or refractory marginal zone lymphoma (MZL) who have received at least one anti-CD20-based regimen, and Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

SELUMETINIB (KOSELUGO™)

Selumetinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2). MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers. In genetically modified mouse models of NF1 that generate neurofibromas that recapitulate the genotype and phenotype of human NF1, oral dosing of selumetinib inhibited ERK phosphorylation, and reduced neurofibroma numbers, volume, and proliferation. 

KOSELUGO is a kinase inhibitor indicated for the treatment of adult and pediatric patients 1 year of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN).

TAZEMETOSTAT (TAZVERIK™)

Tazemetostat is an inhibitor of the methyltransferase, EZH2, and some EZH2 gain-of-function mutations including Y646X, A682G, and A692V. Tazemetostat also inhibited EZH1 with a half-maximal inhibitory concentration (IC50) of 392 nM, approximately 36 times higher than the IC50 for inhibition of EZH2.  The most well-characterized function of EZH2 is as the catalytic subunit of the polycomb repressive complex 2 (PRC2), catalyzing mono-, di-, and trimethylation of lysine 27 of histone H3. Trimethylation of histone H3 leads to transcriptional repression.  SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes can antagonize PRC2 function in the regulation of the expression of certain genes of patients with epithelioid sarcoma. Preclinical in vitro and in vivo models with the loss or dysfunction of certain SWI/SNF complex members (e.g., integrase interactor 1 [INI1/SNF5/SMARCB1/BAF47], SMARCA4, and SMARCA2) can lead to aberrant EZH2 activity or expression and a resulting oncogenic dependence on EZH2. Tazemetostat suppressed proliferation of B-cell lymphoma cell lines in vitro and demonstrated antitumor activity in a mouse xenograft model of B-cell lymphoma with or without EZH2 gain-of-function mutations. Tazemetostat demonstrated greater effects on the inhibition of proliferation of lymphoma cell lines with mutant EZH2.

TAZVERIK is indicated for the treatment of:

Adults and pediatric patients aged 16 years and older with metastatic or locally advanced epithelioid sarcoma not eligible for complete resection.

Adult patients with relapsed or refractory follicular lymphoma whose tumors are positive for an EZH2 mutation as detected by an FDA-approved test and who have received at least 2 prior systemic therapies.

Adult patients with relapsed or refractory follicular lymphoma who have no satisfactory alternative treatment options.

TUCATINIB (TUKYSA™)

Tucatinib is a tyrosine kinase inhibitor of HER2. In vitro, tucatinib inhibits phosphorylation of HER2 and HER3, resulting in inhibition of downstream MAPK and AKT signaling and cell proliferation, and showed anti-tumor activity in HER2 expressing tumor cells. In vivo, tucatinib inhibited the growth of HER2 expressing tumors. The combination of tucatinib and trastuzumab showed increased anti-tumor activity in vitro and in vivo compared to either drug alone. TUKYSA is indicated in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

TUKYSA is indicated:

in combination with trastuzumab and capecitabine for treatment of adult patients with advanced unresectable or metastatic HER2-positive breast cancer, including patients with brain metastases, who have received one or more prior anti-HER2-based regimens in the metastatic setting.

in combination with trastuzumab for the treatment of adult patients with RAS wild-type HER2-positive unresectable or metastatic colorectal cancer that has progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy.

PEMIGATINIB (PEMAZYRE™)

Pemigatinib is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC50 values of less than 2 nM. Pemigatinib also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. Pemigatinib inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Pemigatinib exhibited anti-tumor activity in mouse xenograft models of human tumors with FGFR1, FGFR2, or FGFR3 alterations resulting in constitutive FGFR activation including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2Transformer-2 beta homolog (TRA2b) fusion protein. PEMAZYRE is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. It is also indicated for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement.

GEFITINIB (IRESSA®)

Gefitinib reversibly inhibits the kinase activity of wild-type and certain activating mutations of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signaling and blocking EGFR-dependent proliferation. Gefitinib binding affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than its affinity for the wild-type EGFR. Gefitinib also inhibits IGF and PDGF-mediated signaling at clinically relevant concentrations; inhibition of other tyrosine kinase receptors has not been fully characterized.

Gefitinib is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test.

RIPRETINIB (QINLOCK™)

Ripretinib is a tyrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase (KIT) and platelet derived growth factor receptor A (PDGFRA) kinase, including wild type, primary, and secondary mutations. Ripretinib also inhibits other kinases in vitro, such as PDGFRB, TIE2, VEGFR2, and BRAF.

Ripretinib is indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with 3 or more kinase inhibitors, including imatinib.

SELPERCATINIB (RETEVMO™)

Selpercatinib is a kinase inhibitor. Selpercatinib inhibited wild-type RET and multiple mutated RET isoforms as well as VEGFR1 and VEGFR3 with IC50 values ranging from 0.92 nM to 67.8 nM. In other enzyme assays, selpercatinib also inhibited FGFR 1, 2, and 3 at higher concentrations that were still clinically achievable. In cellular assays, selpercatinib inhibited RET at approximately 60-fold lower concentrations than FGFR1 and 2 and approximately 8-fold lower concentration than VEGFR3.

Selpercatinib is indicated for the treatment of:

Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test

Adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy

Adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate)

Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options

CAPMATINIB (TABRECTA™)

Capmatinib is a kinase inhibitor that targets MET, including the mutant variant produced by exon 14 skipping. MET exon 14 skipping results in a protein with a missing regulatory domain that reduces its negative regulation leading to increased downstream MET signaling. Capmatinib inhibited cancer cell growth driven by a mutant MET variant lacking exon 14 at clinically achievable concentrations and demonstrated anti-tumor activity in murine tumor xenograft models derived from human lung tumors with either a mutation leading to MET exon 14 skipping or MET amplification. Capmatinib inhibited the phosphorylation of MET triggered by binding of hepatocyte growth factor or by MET amplification, as well as MET mediated phosphorylation of downstream signaling proteins and proliferation and survival of MET-dependent cancer cells.

Capmatinib is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping as detected by an FDA approved test.

TRETINOIN CAPSULES

Tretinoin is a retinoid that induces maturation of acute promyelocytic leukemia (APL) cells in culture. Tretinoin is not a cytolytic agent but instead induces cytodifferentiation and decreased proliferation of Acute Promyelocytic Leukemia APL cells in culture and in vivo. In APL patients, tretinoin treatment produces an initial maturation of the primitive promyelocytes derived from the leukemic clone, followed by a repopulation of the bone marrow and peripheral blood by normal, polyclonal hematopoietic cells in patients achieving complete remission (CR). The exact mechanism of action of tretinoin in APL is unknown.

PRALSETINIB (GAVRETO™)

Pralsetinib is a kinase inhibitor of wild-type RET and oncogenic RET fusions (CCDC6-RET) and mutations (RET V804L, RET V804M and RET M918T) with half maximal inhibitory concentrations (IC50s) less than 0.5 nM.  In purified enzyme assays, pralsetinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRB, and FGFR1 at higher concentrations that were still clinically achievable at Cmax. In cellular assays, pralsetinib inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively.

GAVRETO is a kinase inhibitor indicated for treatment of:

• Adult patients with metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer as detected by an FDA approved test (NSCLC).
• Adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).
• This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
  

AZACITIDINE (ONUREG®)

Azacitidine is a pyrimidine nucleoside analog of cytidine that inhibits DNA/RNA methyltransferases. Azacitidine is incorporated into DNA and RNA following cellular uptake and enzymatic biotransformation to nucleotide triphosphates.

Azacitidine is indicated for continued treatment of adult patients with acute myeloid leukemia who achieved first complete remission (CR) or complete remission with incomplete blood count recovery (CRi) following intensive induction chemotherapy and are not able to complete intensive curative therapy.

DECITABINE AND CEDAZURIDINE (INQOVI®)

Decitabine is a nucleoside metabolic inhibitor that is believed to exert its effects after phosphorylation and direct incorporation into DNA and inhibition of DNA methyltransferase, causing hypomethylation of DNA and cellular differentiation and/or apoptosis. Cytidine deaminase (CDA) is an enzyme that catalyzes the degradation of cytidine, including the cytidine analog decitabine. High levels of CDA in the gastrointestinal tract and liver degrade decitabine and limit its oral bioavailability. Cedazuridine is a CDA inhibitor. Administration of cedazuridine with decitabine increases systemic exposure of decitabine.

Decitabine and cedazuridine is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.

RELUGOLIX (ORGOVYX™)

Relugolix is an oral GnRH receptor antagonist that competitively binds to the GnRH receptor, resulting in reduced release of LH, FHS, and consequently testosterone. Clinical trials have shown its effect in testosterone suppression to castrate levels (50ng/dl) which was sustained through 48 weeks in 96.7% in advanced prostate cancer patients along with a confirmed PSA response by day 15 observed in 79.4% of the study group. 

Relugolix is indicated for the treatment of advanced metastatic prostate cancer.

TEPOTINIB (TEPMETKO®)

Tepotinib is an oral kinase inhibitor that targets MET, including variants with exon 14 skipping alterations. Tepotinib inhibits hepatocyte growth factor (HGF) dependent and independent MET phosphorylation and MET-dependent downstream signaling pathways. In vitro, tepotinib inhibited tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent tumor cells. In mice implanted with tumor cell lines with oncogenic activation of MET, including METex14 skipping alterations, tepotinib inhibited tumor growth, led to sustained inhibition of MET phosphorylation, and, in one model, decreased the formation of metastases.

TEPMETKO is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

UMBRALISIB (UKONIQ™)

Umbralisib inhibits multiple kinases. In biochemical and cell-based assays, umbralisib inhibited PI3Kδ and casein kinase CK1ε. PI3Kδ is expressed in normal and malignant B-cells; CK1ε has been implicated in the pathogenesis of cancer cells, including lymphoid malignancies. Umbralisib also inhibited a mutated form of ABL1 in biochemical assays. Umbralisib inhibited cell proliferation, CXCL12-mediated cell adhesion, and CCL19-mediated cell migration in lymphoma cell lines in studies conducted in vitro.

Umbralisib is indicated for the treatment of adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least 1 prior anti-CD20-based regimen and relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

FOTIVDA® (TIVOZANIB)

FOTIVDA is a kinase inhibitor indicated for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies.

LUMAKRAS™ (SOTORASIB)

LUMAKRAS is an inhibitor of the RAS GTPase family indicated for: 

• KRAS G12C-mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
• As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. 
• This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). 
• KRAS G12C-mutated Metastatic Colorectal Cancer (mCRC) In combination with panitumumab, for the treatment of adult patients with KRAS G12C-mutated mCRC as determined by an FDA approved-test, who have received prior fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy. 
  

TRUSELTIQ™ (INFIGRATINIB)

TRUSELTIQ is a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

VALCHLOR® (MECHLORETHAMINE)

VALCHLOR is an alkylating drug indicated for the topical treatment of Stage IA and IB mycosis fungoides‐type cutaneous T‐cell lymphoma in patients who have received prior skin‐directed therapy

TARGRETIN® (BEXAROTENE)

TARGRETIN (bexarotene) is a retinoid indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in patients who are refractory to at least one prior systemic therapy

EXKIVITY™ (mobocertinib)

EXKIVITY is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s)

WELIREG™ (belzutifan)

WELIREG is a hypoxia-inducible factor inhibitor indicated: 

von Hippel-Lindau (VHL) disease - for treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. 

Advanced Renal Cell Carcinoma (RCC) - for treatment of adult patients with advanced renal cell carcinoma (RCC) with a clear cell component following a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). 

Pheochromocytoma or Paraganglioma (PPGL) - for treatment of adult and pediatric patients 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). (

BESREMI® (ROPEGINTERFERON ALFA-2B-NJFT)

BESREMI is indicated for the treatment of adults with polycythemia vera.

Interferon alfa belongs to the class of type I interferons, which exhibit their cellular effects in polycythemia vera in the bone marrow by binding to a transmembrane receptor termed interferon alfa receptor (IFNAR). Binding to IFNAR initiates a downstream signaling cascade through the activation of kinases, in particular Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) and activator of transcription (STAT) proteins. Nuclear translocation of STAT proteins controls distinct gene-expression programs and exhibits various cellular effects. The actions involved in the therapeutic effects of interferon alfa in polycythemia vera are not fully elucidated.

SCEMBLIX® (ASCIMINIB)

SCEMBLIX is a kinase inhibitor indicated for the treatment of adult patients with: 

Newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP). This indication is approved under accelerated approval based on major molecular response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in a confirmatory trial(s). 

Previously treated Ph+ CML in CP. 

Ph+ CML in CP with the T315I mutation. 

VONJO™ (PACRITINIB)

VONJO is a kinase inhibitor indicated for the treatment of adults with intermediate or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L. This indication is approved under accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Pacritinib is an oral kinase inhibitor with activity against wild type Janus associated kinase 2 (JAK2), mutant JAK2V617F, and FMS-like tyrosine kinase 3 (FLT3), which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. MF is often associated with dysregulated JAK2 signaling. Pacritinib has higher inhibitory activity for JAK2 compared to JAK3 and TYK2. At clinically relevant concentrations, pacritinib does not inhibit JAK1. Pacritinib exhibits inhibitory activity against additional cellular kinases (such as CSF1R and IRAK1) the clinical relevance of which is unknown.

ALITRETINOIN (PANRETIN®)

Alitretinoin (9-cis-retinoic acid) is a naturally -occurring endogenous retinoid that binds to and activates all known intracellular retinoid receptor subtypes (RARα, RARβ, RARγ, RXRα, RXRβ and RXRγ). Once activated these receptors function as transcription factors that regulate the expression of genes that control the process of cellular differentiation and proliferation in both normal and neoplastic cells. Alitretinoin inhibits the growth of Kaposi's sarcoma (KS) cells in vitro.

Panretin gel is indicated for topical treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma.

KRAZATI™ (ADAGRASIB)

Adagrasib is an irreversible inhibitor of KRAS G12C that covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state that prevents downstream signaling without affecting wild-type KRAS protein. Adagrasib inhibits tumor cell growth and viability in cells harboring KRAS G12C mutations and results in tumor regression in KRAS G12C-mutated tumor xenograft models with minimal off-target activity.

KRAZATI is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDAapproved test who have received at least one prior systemic therapy.

LYTGOBI® (FUTIBATINIB)

Futibatinib is a small molecule kinase inhibitor of FGFR 1, 2, 3, and 4 with IC50 values of less than 4 Nm. Futibatinib covalently binds FGFR. Constitutive FGFR signaling can support the proliferation and survival of malignant cells. Futibatinib inhibited FGFR phosphorylation and downstream signaling and decreased cell viability in cancer cell lines with FGFR alterations including FGFR fusions/rearrangements, amplifications, and mutations. Futibatinib demonstrated anti-tumor activity in mouse and rat xenograft models of human tumors with activating FGFR genetic alterations.

LYTGOBI is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.

REZLIDHIA™ (OLUTASIDENIB)

Olutasidenib is a small-molecule inhibitor of mutated isocitrate dehydrogenase-1 (IDH1). In patients with AML, susceptible IDH1 mutations are defined as those leading to increased levels of 2-hydroxyglutarate (2-HG) in the leukemia cells and where efficacy is predicted by 1) clinically meaningful remissions with the recommended dose of olutasidenib and/or 2) inhibition of mutant IDH1 enzymatic activity at concentrations of olutasidenib sustainable at the recommended dosage according to validated methods. The most common of such mutations in patients with AML are R132H and R132C substitutions.In vitro, olutasidenib inhibited mutated IDH1 R132H, R132L, R132S, R132G, and R132C proteins; wild-type IDH1 or mutated IDH2 proteins were not inhibited. Olutasidenib inhibition of mutant IDH1 led to decreased 2-HG levels in vitro and in in vivo xenograft models.

REZLIDHIA is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML)

with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-approved test.

JAYPIRCA™ (PIRTOBRUTINIB)

Pirtobrutinib is a small molecule, noncovalent inhibitor of BTK. BTK is a signaling protein of the B-cell antigen receptor (BCR) and cytokine receptor pathways. In B-cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. Pirtobrutinib binds to wild type BTK and BTK harboring C481 mutations, leading to inhibition of BTK kinase activity. In nonclinical studies, pirtobrutinib inhibited BTK-mediated B-cell CD69 expression and inhibited malignant B-cell proliferation. Pirtobrutinib showed dose-dependent anti-tumor activities in BTK wild type and BTK C481S mutant mouse xenograft models.

• Adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
• Adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor.

ORSERDU™ (ELACESTRANT)
Elacestrant is an estrogen receptor antagonist that binds to estrogen receptor-alpha (ERα). In ERpositive (ER+) HER2-negative (HER2-) breast cancer cells, elacestrant inhibited 17β-estradiol mediated  cell proliferation at concentrations inducing degradation of ERα protein mediated through proteasomal  pathway. Elacestrant demonstrated in vitro and in vivo antitumor activity including in ER+ HER2- breast cancer models resistant to fulvestrant and cyclin dependent kinase 4/6 inhibitors and those harboring estrogen receptor 1 gene (ESR1) mutations.

ORSERDU is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, ESR1-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.

AKEEGA™ (niraparib and abiraterone acetate)

Niraparib is an inhibitor of PARP enzymes, including PARP-1 and PARP-2, that play a role in DNA repair. In vitro studies have shown that niraparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death. Increased niraparib-induced cytotoxicity was observed in tumor cell lines with or without deficiencies in BRCA1/2. Niraparib decreased tumor growth in mouse xenograft models of human cancer cell lines with deficiencies in BRCA1/2 and in human patient-derived xenograft tumor models with homologous recombination deficiency (HRD) that had either mutated or wild-type BRCA1/2. Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is expressed in testicular, adrenal, and prostatic tumor tissues and is required for androgen biosynthesis. CYP17 catalyzes two sequential reactions: 1) the conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by 17α-hydroxylase activity and 2) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 lyase activity. DHEA and androstenedione are androgens and are precursors of testosterone. Inhibition of CYP17 by abiraterone can also result in increased mineralocorticoid production by the adrenals [see Warnings and Precautions (5.9)]. Androgen sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with GnRH agonists or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumor. Abiraterone decreased serum testosterone and other androgens in patients in the placebo-controlled clinical trial. It is not necessary to monitor the effect of abiraterone on serum testosterone levels. Changes in serum prostate specific antigen (PSA) levels may be observed but have not been shown to correlate with clinical benefit in individual patients. In mouse xenograft models of prostate cancer, the combination of niraparib and abiraterone acetate increased anti-tumor activity when compared to either drug alone.

AKEEGA is a combination of niraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, a CYP17 inhibitor indicated with prednisone for the treatment of adult patients with:

• deleterious or suspected deleterious BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC).
• deleterious or suspected deleterious BRCA-mutated (BRCAm) metastatic castration-resistant prostate cancer (mCRPC).
• Select patients for therapy based on an FDA-approved test for AKEEGA.

OJJAARA (momelotinib)

Momelotinib is an inhibitor of wild type Janus Kinase 1 and 2 (JAK1/JAK2) and mutant JAK2V617F, which contribute to signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function. Momelotinib and its major human circulating metabolite, M21, have higher inhibitory activity for JAK2 compared to JAK3 and tyrosine kinase 2 (TYK2). Momelotinib and M21 additionally inhibit activin A receptor type 1 (ACVR1), also known as activin receptor like kinase 2 (ALK2), which produces subsequent inhibition of liver hepcidin expression and increased iron availability resulting in increased red blood cell production. MF is a myeloproliferative neoplasm associated with constitutive activation and dysregulated JAK signaling that contributes to inflammation and hyperactivation of ACVR1. JAK signaling recruits and activates STAT (signal transducers and activation of transcription) proteins resulting in nuclear localization and subsequent regulation of gene transcription. 

OJJAARA is a kinase inhibitor indicated for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF or secondary MF [post-polycythemia vera (PV) and post-essential thrombocythemia (ET)], in adults with anemia.

VANFLYTA® (quizartinib)

The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of quizartinib have not been fully characterized. Cardiac Electrophysiology In vitro studies have shown that quizartinib is a predominant inhibitor of the slow delayed rectifier potassium current, IKs. The exposure-response analysis predicted a concentration-dependent QTcF interval median prolongation of 18 and 24 ms [upper bound of 2-sided 90% confidence interval (CI): 21 and 27 ms] at the median steady-state Cmax of quizartinib at the 26.5 mg and 53 mg dose level during maintenance therapy

VANFLYTA is a kinase inhibitor indicated in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive as detected by an FDA-approved test. 
Limitations of Use: VANFLYTA is not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT); improvement in overall survival with VANFLYTA in this setting has not been demonstrated.

AUGTYRO™ (repotrectinib)

Repotrectinib is an inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and of the tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. Fusion proteins that include ROS1 domains can drive tumorigenic potential through hyperactivation of downstream signaling pathways leading to unconstrained cell proliferation. Repotrectinib exhibited anti-tumor activity in cultured cells expressing ROS1 fusions and mutations including SDC4-ROS1, SDC4-ROS1G2032R, CD74-ROS1, CD74-ROS1G2032R, CD74-ROS1D2033N, and CD74-ROS1L2026M.

AUGTYRO is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

FRUZAQLA™ (fruquintinib)

Fruquintinib is a small molecule kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3 with IC50 values of 33, 35, and 0.5 nM, respectively. In vitro studies showed fruquintinib inhibited VEGF-mediated endothelial cell proliferation and tubular formation. In vitro and in vivo studies showed fruquintinib inhibited VEGF-induced VEGFR-2 phosphorylation. In vivo studies showed fruquintinib inhibited tumor growth in a tumor xenograft mouse model of colon cancer.

FRUZAQLA is a kinase inhibitor indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine‑, oxaliplatin‑, and irinotecan‑based chemotherapy, an anti‑VEGF therapy, and, if RAS wild‑type and medically appropriate, an anti-EGFR therapy.

IWILFIN™ (eflornithine)

Eflornithine is an irreversible inhibitor of the enzyme ornithine decarboxylase (ODC), the first and rate-limiting enzyme in the biosynthesis of polyamines and a transcriptional target of MYCN. Polyamines are involved in differentiation and proliferation of mammalian cells and are important for neoplastic transformation. Inhibition of polyamine synthesis by eflornithine restored the balance of the LIN28/Let-7 metabolic pathway, which is involved in regulation of cancer stem cells and glycolytic metabolism, by decreasing expression of the oncogenic drivers MYCN and LIN28B in MYCN-amplified neuroblastoma. In vitro, eflornithine induced senescence and suppressed neurosphere formation in MYCN-amplified and MYCN non-amplified neuroblastoma cells, indicating a cytostatic effect. Treatment with eflornithine prevented or delayed tumor formation in mice injected with limiting dilutions of MYCN-amplified neuroblastoma cells.

IWILFIN is an ornithine decarboxylase inhibitor indicated to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma (HRNB) who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy.

OGSIVEO® (nirogacestat)

Nirogacestat is a gamma secretase inhibitor that blocks proteolytic activation of the Notch receptor. When dysregulated, Notch can activate pathways that contribute to tumor growth.

OGSIVEO is a gamma secretase inhibitor indicated for adult patients with progressing desmoid tumors who require systemic treatment.

TRUQAP™ (capivasertib)

Capivasertib is an inhibitor of all 3 isoforms of serine/threonine kinase AKT (AKT1, AKT2 and AKT3) and inhibits phosphorylation of downstream AKT substrates. AKT activation in tumors is a result of activation of upstream signaling pathways, mutations in AKT1, loss of phosphatase and tensin homolog (PTEN) function and mutations in the catalytic subunit alpha of phosphatidylinositol 3-kinase (PIK3CA). In vitro, capivasertib reduced growth of breast cancer cell lines including those with relevant PIK3CA or AKT1 mutations or PTEN alteration. In vivo, capivasertib alone and in combination with fulvestrant inhibited tumor growth of mouse xenograft models including estrogen receptor positive breast cancer models with alterations in PIK3CA, AKT1, and PTEN.

TRUQAP is a kinase inhibitor indicated, in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations as detected by an FDA-approved test following progression on at least one endocrine-based regimen in the metastatic setting or recurrence on or within 12 months of completing adjuvant therapy.

VORANIGO® (Vorasidenib)

Vorasidenib is a small molecule inhibitor that targets isocitrate dehydrogenase-1 and 2 (IDH1 and IDH2) enzymes. In vitro, vorasidenib inhibited the IDH1 wild type and mutant variants, including R132H and the IDH2 wild type and mutant variants. In cell-based and in vivo tumor models expressing IDH1 or IDH2 mutated proteins, vorasidenib decreased production of 2-hydroxyglutarate (2-HG) and partially restored cellular differentiation.

VORANIGO is an isocitrate dehydrogenase-1 (IDH1) and isocitrate dehydrogenase-2 (IDH2) inhibitor indicated for the treatment of adult and pediatric patients 12 years and older with Grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery including biopsy, sub-total resection, or gross total resection. 

LAZCLUZE™ (lazertinib)