Medicare Advantage

Medical Policy

Notification

Durvalumab (Imfinzi®) and Tremelimumab-actl (Imjudo®)

Notification Issued Date:

This version of the policy will become effective 09/14/2020.

New

policy number MA08.123 supersedes MA08.010j for durvalumab (Imfinzi™).

The following criteria have been revised in this policy:

endothelial bladder cancer and primary carcinoma of the urethra in accordance with National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium® 5.2020

The following criteria have been

added

to this policy:

non-small cell carcinoma and small cell carcinoma in accordance with FDA labeling 06/05/2020 and NCCN Drugs and Biologics Compendium® 5.2020.

The following ICD-10 CM codes have been

added

to this policy:

C33 Malignant neoplasm of trachea

C34.00 Malignant neoplasm of unspecified main bronchus

C34.01 Malignant neoplasm of right main bronchus

C34.02 Malignant neoplasm of left main bronchus

C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung

C34.11 Malignant neoplasm of upper lobe, right bronchus or lung

C34.12 Malignant neoplasm of upper lobe, left bronchus or lung

C34.2 Malignant neoplasm of middle lobe, bronchus or lung

C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung

C34.31 Malignant neoplasm of lower lobe, right bronchus or lung

C34.32 Malignant neoplasm of lower lobe, left bronchus or lung

C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus

Title:

Durvalumab (Imfinzi®) and Tremelimumab-actl (Imjudo®)

Policy #:

MA08.123e

Policy

In the absence of coverage criteria from applicable Medicare statutes, regulations, NCDs, LCDs, CMS manuals, or other Medicare coverage documents, this policy uses internal coverage criteria developed by the Company in consideration of peer-reviewed medical literature, clinical practice guidelines, and/or regulatory status.

The Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition.

INDEX OF MEDICALLY NECESSARY INDICATIONS

This policy addresses numerous medically necessary indications for the use of

durvalumab (

Imfinzi^®) and

tremelimumab-actl (

Imjudo^®) (listed in order of appearance within the Policy section). Please see below for the specific medical necessity criteria. (NOTE: Experimental/Investigational section below must also be reviewed.)

Type of Cancer	Subtype of Cancer
Ampullary Adenocarcinoma
Biliary Tract Cancers	Gallbladder Cancer Extrahepatic Cholangiocarcinoma Intrahepatic Cholangiocarcinoma
Bladder Cancer
Cervical Cancer
Endometrial Carcinoma
Esophageal and Esophagogastric Cancer
Gastric Cancer
Hepatocellular Carcinoma
Malignant Mesothelioma of Pleura
Non-Small Cell Lung Carcinoma
Small Cell Lung Carcinoma

MEDICALLY NECESSARY

AMPULLARY ADENOCARCINOMA

Durvalumab (

Imfinzi), in combination with gemcitabine and cisplatin, is considered medically necessary and, therefore, covered as a first-line therapy for

ampullary adenocarcinoma when the individual meets ALL of the following:

Good Eastern Cooperative Oncology Group (ECOG) performance status (PS) (PS 0-1)
Good biliary drainage
Adequate nutritional intake
Metastatic pancreatobiliary and mixed type disease

BILIARY TRACT CANCERS
Gallbladder Cancer

Durvalumab (Imfinzi), in combination with gemcitabine and cisplatin (or carboplatin if ineligible for cisplatin), is considered medically necessary and, therefore, covered for the treatment of gallbladder cancer for ANY of the following:

As primary systemic treatment for unresectable or gross residual (R2) disease, or metastatic disease
As systemic therapy for individuals who developed recurrent disease more than 6 months after surgery with curative intent and more than 6 months after completion of adjuvant therapy
Subsequent treatment for progression on or after systemic treatment for unresectable or gross residual (R2) disease, or metastatic disease in those who have not been previously treated with a checkpoint inhibitor
As neoadjuvant systemic therapy for resectable locally advanced disease that presents as ONE of the following:

Incidental finding of suspicious mass during surgery where hepatobiliary surgery expertise unavailable
Incidental finding on pathologic review (cystic duct node positive)
Mass on imaging

Intrahepatic and Extrahepatic

Cholangiocarcinoma

Durvalumab (

Imfinzi), in combination with gemcitabine and cisplatin (or carboplatin if ineligible for cisplatin), is considered medically necessary and, therefore, covered for the treatment of intrahepatic and extrahepatic

cholangiocarcinoma for ANY of the following:

As primary systemic treatment for unresectable or gross residual (R2) disease, or metastatic disease
As systemic therapy for individuals who developed recurrent disease more than 6 months after surgery with curative intent and more than 6 months after completion of adjuvant therapy
Subsequent treatment for progression on or after systemic treatment for unresectable or gross residual (R2) disease, or metastatic disease in those who have not been previously treated with a checkpoint inhibitor

BLADDER CANCER

Durvalumab (

Imfinzi), in combination with

neoadjuvant gemcitabine and cisplatin (National Comprehensive Cancer Network [NCCN] preferred), or other cisplatin-based combination chemotherapy, is considered medically necessary and, therefore, covered as perioperative/sandwich immunotherapy for muscle-invasive bladder cancer prior to cystectomy, followed by postoperative

durvalumab (

Imfinzi) for ANY of the following:

Stage II (cT2, N0) disease followed by radical cystectomy
Stage II (cT2, N0) disease followed by partial cystectomy for highly selected individuals with solitary lesion in a suitable location; no carcinoma in situ (CIS)
Stage IIIA (cT3, N0; cT4a, N0; cT1-4a, N1) disease followed by radical cystectomy

CERVICAL CANCER

Durvalumab (

Imfinzi) is considered medically necessary and, therefore, covered for persistent, recurrent, or metastatic small cell neuroendocrine carcinoma of the cervix (NECC) when the individual meets BOTH of the following:

ONE of the following lines of therapy:

First-line
Second-line
Subsequent therapy (if not used previously as first line)

In combination with ONE of the following regimens, and durvalumab (Imfinzi) continued as single agent for maintenance:

Cisplatin and etoposide
Carboplatin and etoposide

ENDOMETRIAL CARCINOMA

Durvalumab (

Imfinzi), in combination with carboplatin and paclitaxel^, and

durvalumab (

Imfinzi) continued as single agent for maintenance therapy (NCCN preferred), is considered medically necessary and, therefore, covered for individuals with stage III-IV deficient mismatch repair (

dMMR)

endometrioid adenocarcinoma in ONE of the following:

As primary treatment in ONE of the following:

Preoperatively for individuals presenting with abdominal/pelvic-confined disease that is suitable for primary surgery
With or without external beam radiation therapy (EBRT), stereotactic body radiation therapy, and/or total hysterectomy/bilateral salpingo-oophorectomy (TH/BSO) for distant metastases that are suitable for primary surgery
With sequential EBRT and with or without brachytherapy for locoregional extrauterine disease that is not suitable for primary surgery
For locoregional extrauterine disease or distant metastases that are not suitable for primary surgery

As adjuvant treatment with or without EBRT and with or without vaginal brachytherapy

Durvalumab (

Imfinzi), in combination with carboplatin and paclitaxel^^, and

durvalumab (

Imfinzi) continued as single agent for maintenance therapy (NCCN preferred), is considered medically necessary and, therefore, covered for

dMMR endometrial carcinoma in ONE of the following:

As first-line therapy (or second-line or subsequent therapy for recurrent disease as clinically appropriate if not used previously) when BOTH of the following are met:

Tumor histology is ONE of the following:

Serous carcinoma
Clear cell carcinoma
Carcinosarcoma
Endometrioid adenocarcinoma
Undifferentiated/dedifferentiated carcinoma

As ONE of the following:

For isolated metastases (except as first-line therapy)
For disseminated metastases with or without sequential palliative EBRT
With sequential EBRT and with or without brachytherapy for locoregional recurrence in individuals with no prior radiation therapy (RT) to site of recurrence, or previous vaginal brachytherapy only
After surgical exploration, with sequential EBRT for locoregional recurrence in individuals with disease confined to the vagina or paravaginal soft tissue, or in pelvic or para-aortic lymph nodes
After surgical exploration, with or without sequential EBRT for locoregional recurrence in individuals with upper abdominal or peritoneal disease
With or without sequential palliative EBRT or brachytherapy for locoregional recurrence in individuals who have received prior EBRT to site of recurrence

For stage III-IV tumors^ when BOTH of the following are met:

Tumor histology is ONE of the following:

Serous carcinoma
Clear cell carcinoma
Carcinosarcoma
Undifferentiated/dedifferentiated carcinoma

As ONE of the following:

Disease is suitable for primary surgery as additional treatment with or without sequential EBRT and with or without vaginal brachytherapy after TH/BSO
Disease is not suitable for primary surgery as primary treatment with or without sequential EBRT and with or without brachytherapy

^For stage III with measurable disease post-surgery and stage IV with or without measurable disease.

^^For adult individuals with recurrent endometrial carcinoma with or without measurable disease.

ESOPHAGEAL AND ESOPHAGOGASTRIC JUNCTION CANCERS

Durvalumab (

Imfinzi), in combination with

tremelimumab-actl (

Imjudo), is considered medically necessary and, therefore, covered as primary

neoadjuvant immunotherapy for esophageal or

esophagogastric junction adenocarcinoma if the tumor is microsatellite instability-high (MSI-H) or

dMMR and the individual is medically fit for surgery with cT2, N0 (high-risk lesions:

lymphovascular invasion, 3 cm or greater, poorly differentiated), cT1b-cT2, N+ or cT3-cT4a, any N disease.

GASTRIC CANCER

Durvalumab (

Imfinzi), in combination with

tremelimumab-actl (

Imjudo), is considered medically necessary and, therefore, covered as primary

neoadjuvant immunotherapy for gastric adenocarcinoma if the tumor is MSI-H or

dMMR for potentially

resectable

locoregional disease (cT2 or higher, any N) if medically fit for surgery.

HEPATOCELLULAR CARCINOMA
D

urvalumab (

Imfinzi), as a single agent or in combination with

tremelimumab-actl (

Imjudo; NCCN preferred), is considered medically necessary and, therefore, covered for the treatment of hepatocellular carcinoma (HCC) as first-line systemic treatment for individuals with ANY of the following:

Unresectable liver-confined disease and are not a transplant candidate
Extrahepatic/metastatic disease and are deemed ineligible for resection, transplant, or locoregional therapy

Durvalumab (

Imfinzi), in combination with

tremelimumab-actl (

Imjudo)+ or as a single agent++, is considered medically necessary and, therefore, covered as subsequent-line systemic therapy (consider if not previously used) if progression on or after systemic therapy.

+For those who have not been previously treated with anti-cytotoxic T lymphocyte–associated antigen (CTLA) 4-based combinations.
++For those who have not been previously treated with a checkpoint inhibitor.

MALIGNANT MESOTHELIOMA OF PLEURA

Durvalumab (

Imfinzi), in combination with

pemetrexed and a platinum agent, is considered medically necessary and, therefore, covered as first-line treatment of individuals with

unresectable malignant mesothelioma of the pleura.

NON-SMALL CELL LUNG CANCER

Durvalumab (

Imfinzi), as a single agent, is considered medically necessary and, therefore, covered for the treatment of individuals with

unresectable stage II-III non-small cell lung cancer (NSCLC) as consolidation immunotherapy when ALL of the following are met:

PS 0-1
No disease progression after definitive concurrent chemoradiation (for individuals who have received sequential chemoradiation, durvalumab [Imfinzi] can be considered as consolidation immunotherapy)
Histology demonstrates squamous cell carcinoma, adenocarcinoma (with mixed subtypes), or large cell carcinoma
No epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R mutations present

Durvalumab (

Imfinzi), as

neoadjuvant systemic therapy, is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with adenocarcinoma (with mixed subtypes), large cell carcinoma, or squamous cell carcinoma histology when ALL of the following are met:

Resectable (node positive and/or tumors 4 cm or greater) disease
Candidate for immune checkpoint inhibitors
No known EGFR mutations or anaplastic lymphoma kinase (ALK) rearrangements*
In ONE of the following combinations:

Carboplatin and paclitaxel (squamous cell histology)
Cisplatin and gemcitabine (squamous cell histology)
Cisplatin and pemetrexed (nonsquamous cell histology)
Carboplatin and pemetrexed (nonsquamous cell histology)
Carboplatin and gemcitabine (squamous cell histology and not a candidate for cisplatin-based therapy)

Used for ONE of the following:

Operable clinical stage IB (T2a, N0), stage II (T1abc-2ab, N1 or T2b, N0), stage IIB (T3, N0), or stage IIIA (T3, N1) disease with pathologic N0 or N1 disease
Clinical presentation of chest wall, trachea/carina, mediastinum, or diaphragm; T3 invasion, N0-1; resectable T4 invasion, N0-1 disease
Clinical presentation of resectable stage IIIA (T4 [size], N0-1)
Operable T2a-3, N0 or T1-3, N1 nodes positive, M0 findings on mediastinal biopsy
T1-3, N2 nodes positive**, M0 findings on mediastinal biopsy
Clinical presentation of separate pulmonary nodule(s), same lobe (T3, N0-1), or ipsilateral non-primary lobe (T4, N0-1)

Durvalumab (

Imfinzi), as a single agent systemic therapy, is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with completely resected tumors 4 cm or more and/or node positive disease, with stages IB-IIIA (T3-4, N2) who received previous

neoadjuvant

durvalumab (

Imfinzi) plus chemotherapy with no known EGFR mutations or ALK rearrangements.

Durvalumab (

Imfinzi), in combination with

tremelimumab-actl (

Imjudo), is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with adenocarcinoma (with mixed subtypes), large cell carcinoma, or squamous cell carcinoma histology in ONE of the following scenarios:

As treatment for recurrent (excluding locoregional recurrence or symptomatic local disease with no evidence of disseminated disease but including mediastinal lymph node recurrence with prior radiation therapy [RT] ), advanced, or metastatic disease as first-line therapy for programmed death ligand 1 (PD-L1) expression-positive (1-49 percent) tumors that are negative for actionable molecular biomarkers* (may be Kirsten rat sarcoma [KRAS] G12C mutation positive) and no contraindications** to programmed death 1 (PD-1) or PD-L1 inhibitors and PS 0-2 in ONE of the following regimens:

With albumin-bound paclitaxel and carboplatin
With pemetrexed and either carboplatin or cisplatin for nonsquamous cell histology
With gemcitabine and either carboplatin or cisplatin for squamous cell histology

As treatment for recurrent (excluding locoregional recurrence or symptomatic local disease with no evidence of disseminated disease but including mediastinal lymph node recurrence with prior RT), advanced, or metastatic disease when ALL of the following are met:

ALL the following are met:

PS 0-2
No contraindications** to PD-1 or PD-L1 inhibitors
No EGFR exon 19 deletion or L858R, ALK, receptor for tyrosine-protein kinase (RET), or reactive oxygen species (ROS)1 rearrangements

In ONE of the following regimens:

With albumin-bound paclitaxel and carboplatin
With pemetrexed and either carboplatin or cisplatin for nonsquamous cell histology
With gemcitabine and either carboplatin or cisplatin for squamous cell histology

In ONE of the following lines of therapy:

Initial systemic therapy for PD-L1 less than 1 percent and negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
First-line therapy for EGFR exon 20 insertion mutation positive tumors
First-line or subsequent therapy for b-rapidly accelerated fibrosarcoma (BRAF) V600E mutation positive tumors
First-line or subsequent therapy for neurotrophic tropomyosin receptor kinase (NTRK)1/2/3 gene fusion positive tumors
First-line or subsequent therapy for mesenchymal-epithelial transition factor (MET) exon 14 skipping mutation positive tumors
First-line therapy for erythroblastic oncogene B (ERBB2) (human epidermal growth factor receptor [HER]2) mutation positive tumors
First-line therapy for neuregulin (NRG)1 gene fusion positive tumors
Subsequent therapy for EGFR S768I, L861Q, and/or G719X mutation positive tumors and prior afatinib, osimertinib, erlotinib, gefitinib, or dacomitinib therapy

Durvalumab (

Imfinzi), as a single agent, as continuation maintenance therapy for recurrent (excluding

locoregional recurrence or symptomatic local disease with no evidence of disseminated disease but including mediastinal lymph node recurrence with prior RT), advanced, or metastatic disease, is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with adenocarcinoma (with mixed subtypes), large cell carcinoma, or squamous cell carcinoma histology in ONE of the following scenarios:

As treatment for individuals with ALL of the following:

PD-L1 expression 1-49 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
No contraindications** to PD-1 or PD-L1 inhibitors
PS 0-2
Have achieved a response or stable disease following first-line therapy with durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) plus chemotherapy

As treatment for individuals with ALL of the following:

PD-L1 expression less than 1 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
No contraindications** to PD-1 or PD-L1 inhibitors
PS 0-2
Have achieved a tumor response or stable disease following initial systemic therapy with durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) plus chemotherapy

Durvalumab (

Imfinzi), in combination with

pemetrexed, as continuation maintenance therapy for recurrent (excluding

locoregional recurrence or symptomatic local disease with no evidence of disseminated disease but including mediastinal lymph node recurrence with prior RT), advanced, or metastatic disease, is considered medically necessary and, therefore, covered for the treatment of individuals with NSCLC with adenocarcinoma (with mixed subtypes) or large cell carcinoma histology in ONE of the following scenarios:

As treatment for individuals with ALL of the following:

PD-L1 expression 1-49 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
No contraindications** to PD-1 or PD-L1 inhibitors
PS 0-2
Have achieved a response or stable disease following first-line therapy with durvalumab (Imfinzi), tremelimumab-actl (Imjudo), and pemetrexed plus either carboplatin or cisplatin for nonsquamous cell histology

As treatment for individuals with ALL of the following:

PD-L1 expression less than 1 percent tumors that are negative for actionable molecular biomarkers* (may be KRAS G12C mutation positive)
No contraindications** to PD-1 or PD-L1 inhibitors
PS 0-2
Have achieved a tumor response or stable disease following initial systemic therapy with durvalumab (Imfinzi), tremelimumab-actl (Imjudo), and pemetrexed plus either carboplatin or cisplatin for nonsquamous cell histology

*Complete genotyping for EGFR, KRAS, ALK, ROS1, BRAF, NTRK1/2/3, MET, RET, NRG1, and ERBB2 (HER2) via biopsy and/or plasma testing. Treatment is guided by available results and, if unknown, these individuals are treated as though they do not have driver oncogenes

**Contraindications for treatment with PD-1/PD-L1 inhibitors may include active or previously documented autoimmune disease and/or current use of immunosuppressive agents, and some oncogenic drivers (i.e., EGFR exon 19 deletion or exon 21 L858R, ALK, RET, or ROS1 rearrangements), have been shown to be associated with less benefit from PD-1/PD-L1 inhibitors

SMALL CELL LUNG CANCER

Durvalumab (

Imfinzi), in combination with etoposide and either carboplatin or cisplatin followed by single-agent maintenance with

durvalumab (

Imfinzi), is considered medically necessary and, therefore, covered for primary treatment (NCCN preferred) of extensive-stage small cell lung cancer (ES-SCLC) in individuals with ANY of the following:

Without localized symptomatic sites or brain metastases and good PS (PS 0-2)
Without localized symptomatic sites or brain metastases and poor PS (PS 3-4) due to small cell lung cancer (SCLC)
With localized symptomatic sites (used with RT [typically sequential] if spinal cord compression)
With brain metastases

Durvalumab (

Imfinzi), as a single agent (NCCN preferred), is considered medically necessary and, therefore, covered for limited stage SCLC (LS-SCLC) with ALL of the following:

As adjuvant consolidation therapy
No disease progression following systemic therapy with concurrent RT
Good performance status (PS 0-2)
Individual is medically inoperable or decision was made not to pursue surgical resection

EXPERIMENTAL/INVESTIGATIONAL

All other uses for

durvalumab (

Imfinzi) and

tremelimumab-actl (

Imjudo) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the Company medical policy on off-label coverage for prescription drugs and biologics.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the drug.

Guidelines

There is no Medicare coverage determination addressing durvalumab (Imfinzi) and tremelimumab-actl (Imjudo); therefore, the Company policy is applicable.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable Evidence of Coverage, durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) are covered under the medical benefits of the Company’s Medicare Advantage products when the medical necessity criteria listed in this medical policy are met.

THE EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS

The Eastern Cooperative Oncology Group (ECOG), established in 1955, was one of the first groups to coordinate multicenter cancer clinical trials. The National Cancer Institute (NCI) is the primary funding source, and ECOG has evolved from a small consortium of institutions in the eastern United States to one of the largest clinical cancer research organizations in the country. As part of their work in the treatment of cancer, ECOG has developed the ECOG Performance Status (PS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the ECOG PS allows clinicians and researchers to determine an individual’s disease progression in terms of how the activities of daily living (ADL) are affected.

ECOG Performance Status (PS)
Grade	ECOG
0	Fully active, able to carry on all pre-disease performance without restriction
1	Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (eg, light housework, office work)
2	Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50 percent of waking hours
3	Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours
4	Completely disabled. Cannot carry on any self-care: totally confined to bed or chair
5	Dead

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.

US FOOD AND DRUG ADMINISTRATION STATUS

Durvalumab (Imfinzi) was approved by the US Food and Drug Administration (FDA) on May 1, 2017, for the treatment of individuals with locally advanced or metastatic urothelial carcinoma who either have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Supplemental approvals for durvalumab (Imfinzi) have since been issued by the FDA. Durvalumab (Imfinzi) is administered as an intravenous infusion over 60 minutes. The FDA removed the indication for urothelial carcinoma from the drug labeling on July 15, 2021.

Tremelimumab-actl (Imjudo), in combination with durvalumab (Imfinzi), was approved by the FDA on October 21, 2022, for the treatment of adult individuals with unresectable hepatocellular carcinoma (uHCC). On November 10, 2022, the FDA approved tremelimumab-actl (Imjudo), in combination with durvalumab (Imfinzi) and platinum-based chemotherapy, for adult individuals with metastatic non-small cell lung cancer (NSCLC) with no sensitizing epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

PEDIATRIC USE
The safety and effectiveness of durvalumab (Imfinzi) and tremelimumab-actl (Imjudo) have not been established in pediatric individuals.

Description

In a normal immune response, the body can recognize the presence of tumors and mount a response to eradicate them. The process of eradicating a tumor begins with antigen-presenting cells that gather and process the antigens released by tumors. This activates the T cells, which proliferate and attack the tumor.

Tumors have learned to evade the normal immune response by exploiting the immune checkpoint pathway. The programmed death receptor-1 (PD-1) is a checkpoint protein expressed on the membrane of activated T cells. The programmed death ligand-1 (PD-L1) and the programmed death ligand-2 (PD-L2) are checkpoint proteins expressed on tumor cells and tumor-infiltrating immune cells. When PD-L1 and PD-L2 attach to PD-1 receptors on the T cells, the T cells become inhibited and will not attack the tumor; thus, the tumor can continue to proliferate.

Durvalumab (Imfinzi) is a human monoclonal antibody and immune checkpoint inhibitor that binds to PD-L1 on tumor cells and tumor-infiltrating immune cells and blocks the interaction with PD-1 and B7.1 receptors on T cells and antigen-presenting cells. Consequently, the tumor is no longer able to inactivate the T cells and the antitumor response continues.

Cancers develop multiple strategies to evade immune detection and destruction by T cells. Cytotoxic T-lymphocytic–associated protein 4 (CTLA-4) is a coinhibitory molecule that functions to inhibit T-cell activation. Antibodies that block the interaction of CTLA-4 with its ligands B7.1 and B7.2 can enhance immune responses, including antitumor immunity. Tremelimumab-actl (Imjudo) is a CTLA-4–blocking antibody allowing T cells to proliferate and attack the tumor.

DURVALUMAB (IMFINZI) WITH OR WITHOUT TREMELIMUMAB-ACTL (IMJUDO) INDICATIONS

BILIARY TRACT CANCERS
On September 2, 2022, the US Food and Drug Administration (FDA) approved durvalumab (Imfinzi), in combination with gemcitabine and cisplatin, as treatment for adults with locally advanced or metastatic biliary tract cancers.

TOPAZ-1 (NCT03875235) was a multicenter, quadruple-blind, placebo-controlled, phase III study in which treatment-naïve individuals with unresectable or metastatic biliary tract cancers, or individuals with recurrent disease, were randomly assigned, in a 1:1 ratio, to receive either durvalumab (Imfinzi) or placebo, in combination with gemcitabine and cisplatin, followed by durvalumab (Imfinzi) or placebo as monotherapy, until there was either disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).

A total of 685 individuals were randomly assigned to either durvalumab (Imfinzi) (n=341) or placebo (n=344) in combination with gemcitabine and cisplatin. At the time of data cutoff, 198 participants (58.1 percent) in the durvalumab (Imfinzi) cohort and 226 participants (65.7 percent) in the placebo cohort had died. The median OS was 12.8 months in the durvalumab (Imfinzi) cohort and 11.5 months in the placebo cohort (P=0.021). Median PFS was 7.2 months in the durvalumab (Imfinzi) cohort and 5.7 months in the placebo cohort (P=0.001). The ORR was 26.7 percent in the durvalumab (Imfinzi) cohort and 18.7 percent in the placebo cohort. The median DOR at 12 months was 26.1 percent in the durvalumab (Imfinzi) cohort and 15.0 percent in the placebo cohort. The incidence of grade 3 or 4 adverse events was 75.7 percent in the durvalumab (Imfinzi) cohort and 77.8 percent in the placebo cohort.

BLADDER CANCER
On March 28, 2025, the FDA approved durvalumab (Imfinzi), in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent durvalumab (Imfinzi), as adjuvant treatment following radical cystectomy, for the treatment of adults with muscle invasive bladder cancer (MIBC).

The efficacy and safety of durvalumab (Imfinzi) in combination with gemcitabine and cisplatin was evaluated in the NIAGARA clinical trial (NCT03732677). The study was phase III, randomized, multicenter, and open labeled. A total of 533 individuals were randomly assigned to receive durvalumab (Imfinzi) with chemotherapy and 530 to chemotherapy only. A key primary endpoint was event-free survival (EFS). A key secondary endpoint was OS. The EFS at 24 months was 67.8 percent in the durvalumab (Imfinzi) with chemotherapy group versus 59.8 percent in the chemotherapy only group (the hazard ratio [HR] for progression, recurrence, not undergoing a radical cystectomy, or death from any cause was 0.68; 95 percent confidence interval [CI] 0.56–0.82; P<0.001). The OS at 24 months was 82.2 percent in the durvalumab (Imfinzi) with chemotherapy group versus 75.2 percent in the chemotherapy only group (the HR for death was 0.75; 95 percent CI, 0.59–0.93; P=0.01). Grade 3 or 4 adverse events were approximately equal between the two cohorts.

ENDOMETRIAL CARCINOMA
On June 14, 2024, the FDA approved durvalumab (Imfinzi) in combination with carboplatin and paclitaxel followed by durvalumab (Imfinzi) as a single agent, for the treatment of adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).

The efficacy and safety of durvalumab (Imfinzi) in combination with carboplatin and paclitaxel was evaluated in the DUO-E clinical trial (NCT04269200). The study was phase III, randomized, multicenter, double-blinded, and placebo-controlled. Of the 875 individuals enrolled in the study, 95 were in a subgroup of individuals that had dMMR tumors. The primary endpoint was PFS up to 4 years. Key secondary endpoints included ORR and DOR. At the time of data cutoff, the median PFS had not been reached in the durvalumab (Imfinzi) population, but was 7 months in the control arm. The ORR in the durvalumab (Imfinzi) population was 71.4 percent (95 percent CI, 55.4–84.3; 12 percent complete response [CR], 18 percent partial response [PR]). The median DOR was not reached in the durvalumab (Imfinzi) population, but was 10.5 months in the control arm. No new safety concerns were identified.

HEPATOCELLULAR CARCINOMA

On October 21, 2022, the FDA approved durvalumab (Imfinzi), in combination with tremelimumab-actl (Imjudo), for the treatment of adults with unresectable hepatocellular carcinoma (HCC). The Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen consists of a single dose of tremelimumab-actl (Imjudo), plus durvalumab (Imfinzi), followed by durvalumab (Imfinzi) every 4 weeks.

Approval of the combination regimen was based on the results from the phase III, multicenter, open-label HIMALAYA trial (NCT03298451), in which a total of 1171 participants were randomly assigned to durvalumab (Imfinzi; arm 1; n=389), STRIDE (arm 2; n=393), or the standard of care treatment, sorafenib (Nexavar; arm 3; n=389). The primary endpoint was OS in arm 2 versus arm 3. Secondary endpoints included OS in arm 1 versus arm 3, PFS, time to progression (TTP), ORR, and DOR.

The median OS was 16.56 months in arm 1, 16.43 months in arm 2, and 13.77 months in arm 3. PFS was 3.65 months in arm 1, 3.78 months in arm 2, and 4.07 months in arm 3. The median TTP was 3..8 months in arm 1, 5.4 months in arm 2, and 5.6 months in arm 3. The ORR was 17 percent in arm 1, 20.1 percent in arm 2, and 3.1 percent in arm 3. The median DOR was 16.8 months in arm 1, 22.3 months in arm 2, and 18.4 months in arm 3.

NON-SMALL CELL LUNG CANCER
On February 16, 2018, the FDA approved durvalumab (Imfinzi) for individuals with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

The efficacy and safety of durvalumab (Imfinzi) was evaluated in the PACIFIC study (NCT02125461), a multicenter, randomized, double-blind, placebo-controlled phase III study in individuals with unresectable stage III NSCLC who completed at least two cycles of concurrent platinum-based chemotherapy and definitive radiation within 42 days prior to initiation of the study drug and had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. Individuals were randomly assigned in a 2:1 ratio to receive durvalumab (Imfinzi) or placebo every 2 weeks for up to a year or until unacceptable toxicity or confirmed progression. The primary efficacy endpoints were PFS and OS. Secondary endpoints included ORR and DOR.

A total of 713 individuals underwent randomization. A total of 473 individuals received durvalumab (Imfinzi) and 236 individuals received placebo. As of the interim analysis, the median follow-up was 25.2 months. The 24-month OS rate was 66.3 versus 55.6 percent in the durvalumab (Imfinzi) group versus the placebo group (P=0.005). The median PFS was 17.2 versus 5.6 months in the durvalumab (Imfinzi) group versus the placebo group. The ORR was 30 versus 17.8 percent of individuals who attained a complete or partial response in the durvalumab (Imfinzi) group versus the placebo group. The total number of individuals who sustained a grade 3 or 4 adverse event was 30.5 versus 26.1 percent in the durvalumab (Imfinzi) group versus the placebo group.

On November 10, 2022, the FDA approved tremelimumab-actl (Imjudo), in combination with durvalumab (Imfinzi) and platinum-based chemotherapy, for the treatment of adults with metastatic non-small cell lung cancer (mNSCLC) without epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumor aberrations.

The efficacy and safety of tremelimumab-actl (Imjudo), in combination with durvalumab (Imfinzi) and platinum-based chemotherapy, was evaluated in the phase III POSEIDON study (NCT03164616), a randomized, multicenter, open-label comparative study for first-line treatment in individuals with mNSCLC. The POSEIDON study evaluated tremelimumab-actl (Imjudo) plus durvalumab (Imfinzi) and chemotherapy (arm 1) versus durvalumab (Imfinzi) plus chemotherapy (arm 2) versus chemotherapy alone (arm 3) as first-line treatment for mNSCLC. Participants (n=1013) with EGFR/ALK wild-type mNSCLC were randomized (1:1:1) to the three arms. The primary endpoints were PFS and OS in arm 2 versus arm 3. Secondary endpoints included PFS and OS for arm 1 versus arm 3, ORR, and DOR.

The median PFS was significantly improved in arm 2 versus arm 3 (hazard ratio [HR], 0.74; 95 percent CI, 0.62–0.89; P=0.0009; 5.5 vs. 4.8 months). Although median OS in arm 2 was better than in arm 3, it did not reach statistical significance (HR, 0.86; 95 percent CI, 0.72–1.02; P=0.0758; 13.3 vs. 11.7 months). The median 24-month OS for arm 2 versus arm 3 was 29.6 versus 22.1 percent. The median PFS for arm 1 versus arm 3 was 6.2 versus 4.8 months (HR, 0.72; 95 percent CI, 0.60–0.86; P=0.0003). The median OS for arm 1 versus arm 3 was 14.0 versus 11.7 months (HR, 0.77; 95 percent CI, 0.65–0.92; P=0.0030). The 24-month OS was significantly improved in arm 1 versus arm 3, (32.9 vs. 22.1 percent). Treatment-related adverse events (TRAE) were maximum grade 3 or 4 in 51.8, 44.6, and 44.4 percent of participants in arm 1, arm 2, and arm 3, respectively. The percentage of participants that discontinued treatment due to TRAEs was 15.5, 14.1, and 9.9 percent, in arm 1, arm 2, and arm 3, respectively.

On August 15, 2024, the FDA granted approval for durvalumab (Imfinzi), in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by durvalumab (Imfinzi) continued as a single agent as adjuvant treatment after surgery, for the treatment of adults with resectable (tumors 4 cm or greater and/or node positive) NSCLC and no known EGFR mutations or ALK rearrangements.

The efficacy and safety of durvalumab (Imfinzi), in combination with neoadjuvant chemotherapy was evaluated in the AEGEAN clinical trial (NCT03800134). The study was phase III, randomized, multicenter, double-blinded, and placebo controlled. A total of 400 individuals were randomized to treatment with durvalumab (Imfinzi) and 402 to placebo. The primary endpoints were EFS and pathologic complete response (pCR). At the 12-month analysis, EFS was observed in 73.4 percent of the durvalumab (Imfinzi) cohort versus 64.5 percent in the control cohort. The incidence of pCR in the durvalumab (Imfinzi) cohort was 17.2 percent versus 4.3 percent in the control cohort (difference 13.0, 95 percent CI, 8.7 to 17.6; P<0.001). Grade 3 or 4 adverse events were approximately equal between the two cohorts.

SMALL CELL LUNG CANCER
On March 27, 2020, the FDA granted approval for durvalumab (Imfinzi), in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of individuals with extensive-stage small cell lung cancer (ES-SCLC).

The efficacy and safety of durvalumab (Imfinzi), in combination with etoposide and either carboplatin or cisplatin, in previously untreated ES-SCLC was evaluated in the CASPIAN study (NCT03043872), a randomized, multicenter, active-controlled, phase III, open-label trial. Participants were randomly assigned to one of three arms. Individuals in arm 1 received durvalumab (Imfinzi), tremelimumab-actl (Imjudo), a platinum-containing chemotherapy (either carboplatin or cisplatin), and etoposide. Individuals in arm 2 received durvalumab (Imfinzi) plus a platinum-containing chemotherapy (either carboplatin or cisplatin), and etoposide. Individuals in arm 3 received a platinum-containing chemotherapy (either carboplatin or cisplatin) and etoposide. The primary endpoint was OS in arm 1 versus arm 3 and arm 2 versus arm 3. Secondary endpoints were PFS and ORR.

A total of 805 individuals underwent randomization: 268 individuals in arm 1, 268 individuals in arm 2, and 269 individuals in arm 3. The OS was 10.4 months in arm 1 versus 12.9 months in arm 2 versus 10.5 months in arm 3. Median PFS was 4.9 months in arm 1 versus 5.1 months in arm 2 versus 5.4 months in arm 3. The ORR was 74.2 percent in arm 1 versus 79.5 percent in arm 2 versus 70.6 percent in arm 3.

On December 4, 2024, the FDA granted approval for durvalumab (Imfinzi), as a single agent, for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

The efficacy and safety of durvalumab (Imfinzi) was evaluated in the ADRIATIC clinical trial (NCT03703297). The study was phase III, randomized, multicenter, double-blinded, and placebo controlled. A total of 264 individuals were randomly assigned to receive durvalumab (Imfinzi) and 266 to placebo. The coprimary endpoints were OS and PFS. The median OS in the durvalumab (Imfinzi) group was 55.9 months versus 33.4 months in the control group (HR 0.73, 95 percent CI 0.57–0.93; P=0.0104). The median PFS in the durvalumab group was 16.6 months versus 9.2 months in the control group (HR 0.76, 95 percent CI, 0.61–0.95; P=0.0161). Grade 3 or 4 adverse events were approximately equal between the two cohorts.

OFF-LABEL INDICATIONS

There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company's off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.

References

Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8):EVIDoa2100070.

American Hospital Formulary Service (AHFS). Durvalumab (Imfinzi^®). AHFS Drug Information 2025. [UpToDate Lexidrug Web site]. 02/04/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed April 25, 2025.

American Hospital Formulary Service (AHFS). Tremelimumab-actl (Imjudo^®). AHFS Drug Information 2025. [UpToDate Lexidrug Web site]. 02/17/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed April 25, 2025.

Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med. 2018;379(24):2342-2350.

Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer. N Engl J Med. 2024;391(14):1313-1327.

ClinicalTrials.gov. A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage III unresectable non-small cell lung cancer (PACIFIC). ClinicalTrials.gov Identifier: NCT02125461. First Posted: April 29, 2014. Last Update Posted: October 10, 2023. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. A study of neoadjuvant/adjuvant durvalumab for the treatment of patients with resectable non-small cell lung cancer (AEGEAN). ClinicalTrials.gov Identifier: NCT03800134. First Posted: January 11, 2019. Last Update Posted: January 14, 2025. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Durvalumab + gemcitabine/cisplatin (neoadjuvant treatment) and durvalumab (adjuvant treatment) in patients with MIBC (NIAGARA). ClinicalTrials.gov Identifier: NCT03732677. First Posted: November 6, 2018. Last Update Posted: February 25, 2025. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Durvalumab +/- tremelimumab in combination with platinum based chemotherapy in untreated extensive-stage small cell lung cancer (CASPIAN). ClinicalTrials.gov Identifier: NCT03043872. First Posted: February 6, 2017. Last Update Posted: April 17, 2025. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Durvalumab or placebo in combination with gemcitabine/cisplatin in patients with 1st line advanced biliary tract cancer (TOPAZ-1). ClinicalTrials.gov Identifier: NCT03875235. First Posted: March 14, 2019. Last Update: February 25, 2025. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Durvalumab with or without Olaparib as maintenance therapy after first-line treatment of advanced and recurrent endometrial cancer (DUO-E). ClinicalTrials.gov Identifier: NCT04269200. First Posted: February 13, 2020. Last Update Posted: February 11, 2025. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Study of durvalumab + tremelimumab, durvalumab, and placebo in limited stage small-cell lung cancer in patients who have not progressed following concurrent chemoradiation therapy (ADRIATIC). ClinicalTrials.gov Identifier: NCT03703297. First Posted: October 11, 2018. Last Update Posted: February 11, 2025. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Study of durvalumab and tremelimumab as first-line treatment in patients with advanced hepatocellular carcinoma (HIMALAYA). ClinicalTrials.gov Identifier: NCT03298451. First Posted: October 2, 2017. Last Update Posted: December 31, 2024. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Study of durvalumab and tremelimumab with chemotherapy or durvalumab with chemotherapy or chemotherapy alone for patients with lung cancer (POSEIDON). ClinicalTrials.gov Identifier: NCT03164616. First Posted: May 23, 2017. Last Update: March 18, 2025. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

ClinicalTrials.gov. Study of durvalumab with chemoradiotherapy for women with locally advanced cervical cancer (CALLA). ClinicalTrials.gov Identifier: NCT03830866. First Posted February 5, 2019. Last Update Posted: July 26, 2024. Available at: https://clinicaltrials.gov/. Accessed April 25, 2025.

Durvalumab (Imfinzi^®) Package Insert. Wilmington, DE : AstraZeneca Pharmaceuticals LP. 03/2025. Available at: https://www.imfinzi.com/. Accessed April 25, 2025.

Elsevier's Clinical Pharmacology Compendium. Durvalumab (Imfinzi^®). [Clinical Key Web site]. 04/07/2025. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed April 25, 2025.

Elsevier's Clinical Pharmacology Compendium. Tremelimumab-actl (Imjudo^®). [Clinical Key Web site]. 09/20/2024. Available at: https://www.clinicalkey.com/#!/ [via subscription only]. Accessed April 25, 2025.

Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomized, controlled, open-label, phase 3 trial. Lancet Oncol. 2021;22(1):51-65.

Heymach JV, Harpole D, Mitsudomi T, et al. Perioperative durvalumab for resectable non-small-cell lung cancer. N Engl J Med. 2023;389(18):1672-1684.

Johnson ML, Cho BC, Luft A, et al. Durvalumab with or without tremelimumab in combination with chemotherapy as first-line therapy for metastatic non-small-cell lung cancer: the phase III POSEIDON study. J Clin Oncol. 2023;41(6):1213-1227.

Merative Micromedex^® DRUGDEX^® (electronic version). Durvalumab (Imfinzi^®). [Micromedex Web site]. 04/09/2025. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed April 25, 2025.

Merative Micromedex^® DRUGDEX^® (electronic version). Tremelimumab-actl (Imjudo^®). [Micromedex Web site]. 01/27/2025. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® - Ampullary Adenocarcinoma. V2.2025. [NCCN Web site]. 01/10/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/ampullary.pdf. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® - Biliary Tract Cancers. V1.2025. [NCCN Web site]. 03/20/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/btc.pdf. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® - Bladder Cancer. V1.2025. [NCCN Web site]. 03/25/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® - Cervical Cancer. V4.2025. [NCCN Web site]. 03/24/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/cervical.pdf. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® - Esophageal and Esophagogastric Junction Cancers. V3.2025. [NCCN Web site]. 04/22/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® - Gastric Cancer. V2.2025. [NCCN Web site]. 04/04/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® –Hepatocellular Carcinoma. V1.2025. [NCCN Web site]. 03/20/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/hepatobiliary.pdf. [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® – Non-Small Cell Lung Cancer. V3.2025. [NCCN Web site]. 01/14/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® – Small Cell Lung Cancer. V4.2025 [NCCN Web site]. 01/13/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf. [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology^® – Uterine neoplasms. V3.2025 [NCCN Web site]. 03/07/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/uterine.pdf. [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium^®. [NCCN Web site]. Durvalumab (Imfinzi®). Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed April 25, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium^®. [NCCN Web site]. Tremelimumab-actl (Imjudo®). Available at: https://www.nccn.org/professionals/drug_compendium/content/ [via subscription only]. Accessed April 25, 2025.

National Institute for Health and Care Excellence (NICE). TA944: Durvalumab with gemcitabine and cisplatin for treating unresectable or advanced biliary tract cancer. [NICE Web site]. 01/10/2024. Available at: https://www.nice.org.uk/guidance/ta944. Accessed April 25, 2025.

National Institute for Health and Care Excellence (NICE). TA798: Durvalumab for maintenance treatment of unresectable non-small cell lung cancer after platinum-based chemoradiation. [NICE Web site]. 06/22/2022. Available at: https://www.nice.org.uk/guidance/ta798. Accessed April 25, 2025.

Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8):EVIDoa2200015.

Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655.

Ouwens M, Darilay A, Zhang Y, et al. Assessing the influence of subsequent immunotherapy on overall survival in patients with unresectable stage III non-small cell lung cancer from the PACIFIC study. Curr Ther Res Clin Exp. 2021;95:100640.

Paz-Ares L , Dvorkin M, Chen Y, et al. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019;394(10212):1929-1939.

Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. 2024;391(19):1773-1786.

Tremelimumab-actl (Imjudo^®) Package Insert. Wilmington, DE : AstraZeneca Pharmaceuticals LP. 07/2024. Available at: https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/0102c6fd-de8a-4b43-afa3-2a2c2115d472/0102c6fd-de8a-4b43-afa3-2a2c2115d472_viewable_rendition__v.pdf. Accessed April 25, 2025.

UpToDate^® Lexidrug^TM. Durvalumab (Imfinzi^®). [UpToDate Lexidrug Web site]. 04/09/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed April 25, 2025.

UpToDate^® Lexidrug^TM. Tremelimumab-actl (Imjudo^®). [UpToDate Lexidrug Web site]. 03/28/2025. Available at: https://online.lexi.com/lco/action/home [via subscription only]. Accessed April 25, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Durvalumab (Imfinzi^®) Prescribing Information. [FDA Web site]. 03/28/2025. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed April 25, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Tremelimumab-actl (Imjudo^®) Prescribing Information. [FDA Web site]. [FDA Web site]. 01/25/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed April 25, 2025.

Van Coillie S, Wiernicki B, Xu J. Molecular and cellular functions of CTLA-4. Adv Exp Med Biol. 2020;1248:7-32.

Westin SN, Moore K, Chon HS, et al. Durvalumab plus carboplatin/paclitaxel followed by maintenance durvalumab with or without olaparib as first-line treatment for advanced endometrial cancer: the phase III DUO-E trial. J Clin Oncol. 2024 Jan 20;42(3):283-299.

Coding

CPT Procedure Code Number(s)

N/A

ICD - 10 Procedure Code Number(s)

N/A

ICD - 10 Diagnosis Code Number(s)

Report the most appropriate diagnosis code in support of medically necessary criteria as listed in the policy.

HCPCS Level II Code Number(s)

J9173 Injection, durvalumab, 10 mg

J9347 Injection, tremelimumab-actl, 1 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.123e:

07/28/2025

This version of the policy will become effective 07/28/2025.

The following indications have been added to this policy in accordance with the National Comprehensive Cancer Network (NCCN) compendium:

Bladder Cancer V1.2025 (03/25/2025)
Uterine Neoplasms V3.2025 (03/07/2025)

The following policy criteria have been revised in accordance with the NCCN compendium:

Ampullary Adenocarcinoma V2.2025 (01/10/2025)
Biliary Tract Cancers V3.2023 (11/08/2023)
Hepatocellular Carcinoma V1.2025 (03/20/2025)
Non-Small Cell Lung Cancer V2.2024 (02/09/2024)
Small Cell Lung Cancer V4.2025 (01/13/2025)

All ICD-10 codes have been removed from this policy, since they are informational.
Report the most appropiate diagnosis code in support of medically necessary criteria as listed in the policy.

Revisions From MA08.123d:

05/06/2024

This version of the policy will become effective 05/06/2024.

The following indications have been added to this policy in accordance with National Comprehensive Cancer Network (NCCN) compendium accessed 03/06/2024:
Esophageal and Esophagogastric Cancers V4.2023 (01/26/2024)
Gastric Cancer V3.2023 (01/26/2024)

The following policy criteria have been revised in accordance with NCCN compendium:
Ampullary Adenocarcinoma V1.2024 (12/13/2023)
Biliary Tract Cancer V3.2023 (11/08/2023)
Cervical Cancer V2.2024 (02/23/2024)
Hepatocellular Carcinoma V2.2023 (09/14/2023)
Non-Small Cell Lung Cancer V2.2024 (02/09/2024)
Small Cell Lung Cancer V2.2024 (11/21/2023)

The following ICD-10 codes have been added to this policy:
C7A.1, C15.3, C15.4, C15.5, C15.8, C15.9, C16.0, C16.1, C16.2, C16.3, C16.4, C16.5, C16.6, C16.8, C16.9

The following ICD-10 codes have been deleted from this policy:
C34.00, C34.10, C34.30, C34.80, C34.90

Revisions From MA08.123c:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
09/04/2023	This version of the policy will become effective 09/04/2023. Tremelimumab-actl (Imjudo®) has been added to the policy name. The following policy criteria have been added in accordance with NCCN compendium: Ampullary Adenocarcinoma (V1.2023; 04/27/2023) Cervical Cancer (V1.2023; 04/28/2023) The following policy criteria have been added in accordance with Micromedex: Malignant mesothelioma of pleura The following policy criteria have been revised in accordance with NCCN compendium: Biliary Tract Cancers (V2.2023; 05/10/2023) Non-Small Cell Lung Cancer (V3.2023; 04/13/2023) The following ICD-10 CM codes have been added to this policy: C24.1 Malignant neoplasmof ampulla of Vater C45.0 Mesothelioma of pleura C53.1 Malignant neoplasm of exocervix C53.8 Malignant neoplasm of overlapping sites of cervix uteri C53.9 Malignant neoplasm of cervix uteri, unspecified D06.0 Carcinoma in situ of endocervix D06.1 Carcinoma in situ of exocervix D06.7 Carcinoma in situ of other parts of cervix D06.9 Carcinoma in situ of cervix, unspecified The following HCPCS code has been added to this policy: J9347 Injection, tremelimumab-actl, 1 mg

01/01/2024

Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.

09/04/2023

This version of the policy will become effective 09/04/2023.

Tremelimumab-actl (Imjudo®) has been added to the policy name.

The following policy criteria have been added in accordance with NCCN compendium:

Ampullary Adenocarcinoma (V1.2023; 04/27/2023)
Cervical Cancer (V1.2023; 04/28/2023)

The following policy criteria have been added in accordance with Micromedex: Malignant mesothelioma of pleura

The following policy criteria have been revised in accordance with NCCN compendium:

Biliary Tract Cancers (V2.2023; 05/10/2023)
Non-Small Cell Lung Cancer (V3.2023; 04/13/2023)

The following ICD-10 CM codes have been added to this policy:
C24.1 Malignant neoplasmof ampulla of Vater
C45.0 Mesothelioma of pleura
C53.1 Malignant neoplasm of exocervix
C53.8 Malignant neoplasm of overlapping sites of cervix uteri
C53.9 Malignant neoplasm of cervix uteri, unspecified
D06.0 Carcinoma in situ of endocervix
D06.1 Carcinoma in situ of exocervix
D06.7 Carcinoma in situ of other parts of cervix
D06.9 Carcinoma in situ of cervix, unspecified

The following HCPCS code has been added to this policy:

J9347 Injection, tremelimumab-actl, 1 mg

Revisions From MA08.123b:

01/02/2023

This version of the policy will become effective 01/02/2023.
This policy has been updated in consideration of revisions within the US Food and Drug Administration (FDA) labeling:

Coverage was added for the condition of non-small cell lung cancer.
Coverage was added for the condition of hepatocellular carcinoma.

The following policy criteria have been revised in accordance with NCCN compendium:
Hepatobiliary Cancers (V3.2022; 10/14/2022

The following ICD-10 CM codes have been added to this policy:
C22.0 Liver cell carcinoma
C22.1 Intrahepatic bile duct carcinoma
C22.7 Other specified carcinomas of liver
C22.8 Malignant neoplasm of liver, primary, unspecified as to type
C22.9 Malignant neoplasm of liver, not specified as primary or secondary
C23 Malignant neoplasm of gallbladder
C24.0 Malignant neoplasm of extrahepatic bile duct
C24.8 Malignant neoplasm of overlapping sites of biliary tract

C24.9 Malignant neoplasm of biliary tract, unspecified

Revisions From MA08.123a:

01/03/2022

This version of the policy will become effective 01/03/2022.

The following criteria have been deleted from this policy in accordance with US Food and Drug Administration (FDA) labeling (07/15/2021) and National Comprehensive Cancer Network (NCCN) compendium (accessed 10/15/2021):
Urothelial carcinoma

The following policy criteria have been revised in accordance with NCCN compendium:
Non-small cell lung cancer (V5.2021; 06/15/2021)
Small cell lung cancer (V1.2022; 08/09/2021)

The following ICD-10 codes have been removed from this policy:

C61, C65.1, C65.2, C65.9, C66.1, C66.2, C66.9, C67.0, C67.1, C67.2, C67.3, C67.4, C67.5, C67.6, C67.7, C67.8, C67.9, C68.0, C68.1, C68.8, C68.9

Revisions From MA08.123:

09/14/2020

This version of the policy will become effective 09/14/2020.

New policy number MA08.123 supersedes MA08.010j for durvalumab (Imfinzi™).

The following criteria have been revised in this policy:

endothelial bladder cancer and primary carcinoma of the urethra in accordance with National Comprehensive Cancer Network (NCCN) Drugs and Biologics Compendium® 5.2020

The following criteria have been added to this policy:

non-small cell carcinoma and small cell carcinoma in accordance with FDA labeling 06/05/2020 and NCCN Drugs and Biologics Compendium® 5.2020.

The following ICD-10 CM codes have been added to this policy:

C33 Malignant neoplasm of trachea
C34.00 Malignant neoplasm of unspecified main bronchus
C34.01 Malignant neoplasm of right main bronchus
C34.02 Malignant neoplasm of left main bronchus
C34.10 Malignant neoplasm of upper lobe, unspecified bronchus or lung
C34.11 Malignant neoplasm of upper lobe, right bronchus or lung
C34.12 Malignant neoplasm of upper lobe, left bronchus or lung
C34.2 Malignant neoplasm of middle lobe, bronchus or lung
C34.30 Malignant neoplasm of lower lobe, unspecified bronchus or lung
C34.31 Malignant neoplasm of lower lobe, right bronchus or lung
C34.32 Malignant neoplasm of lower lobe, left bronchus or lung
C34.80 Malignant neoplasm of overlapping sites of unspecified bronchus

Version Effective Date:

7/28/2025

Version Issued Date:

7/28/2025

Version Reissued Date: