Medicare Advantage

Medical Policy

Title:

Dostarlimab-gxly (Jemperli)

Policy #:

MA08.136f

Policy

When services can be administered in various settings, 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.

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.

INDEX OF MEDICALLY NECESSARY INDICATIONS

This policy addresses numerous medically necessary indications for the use of dostarlimab-gxly (Jemperli) 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).

CANCER TYPE

Ampullary Adenocarcinoma

Anal Carcinoma

Breast Cancer

Colon Cancer (including

Appendiceal Adenocarcinoma)

Endometrial Cancer

Esophageal and

Esophagogastric Junction Cancers

Gastric Cancer

Occult Primary Cancer

Ovarian/Fallopian Tube/Primary Peritoneal Cancer

Pancreatic Adenocarcinoma

Rectal Cancer

Small Bowel Adenocarcinoma

MEDICALLY NECESSARY

AMPULLARY ADENOCARCINOMA

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the subsequent treatment of adult individuals with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) recurrent or advanced

ampullary adenocarcinoma, as determined by a US Food and Drug Administration (FDA)-approved test, and meet BOTH of the following:

Have progressed on, or following, prior treatment
Have no satisfactory alternative treatment option

ANAL CARCINOMA

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with recurrent or advanced metastatic squamous cell anal carcinoma as second-line and subsequent therapy if no prior immunotherapy received (National Comprehensive Cancer Network [NCCN] preferred)

BREAST CANCER

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with dMMR or MSI-H recurrent or advanced breast cancer, as determined by an FDA-approved test, and meet ALL of the following:

Have progressed on, or following, prior treatment
Have no satisfactory alternative treatment option
ONE of the following is met:

Invasive breast cancer with ALL of the following:

ONE of the following histology types:

Lobular
Mixed
Metaplastic
Ductal/NST
Micropapillary
Pure tubular
Pure mucinous
Pure cribriform
Encapsulated or solid papillary carcinoma
Other rare forms
Adenoid cystic and other salivary carcinomas
Secretory carcinoma
Rare low-grade forms of metaplastic carcinoma

ONE of the following levels of disease:

Recurrent unresectable (local or regional) disease
Stage IV (M1) disease

Inflammatory breast cancer (special consideration) with ONE of the following levels of disease:
- No response to preoperative systemic therapy
- Recurrent unresectable (local or regional) disease
- Stage IV (M1) disease

As ONE of the following:

As third-line therapy and beyond for hormone receptor–positive and human epidermal growth factor receptor 2 (HER2)-negative with visceral crisis or endocrine therapy refractory or for triple-negative breast cancer (TNBC)
As fourth-line and beyond for HER2-positive disease

COLON CANCER (INCLUDING APPENDICEAL ADENOCARCINOMA)

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with dMMR/MSI-H or polymerase epsilon/delta (POLE/POLD1) mutation with ultrahypermutated phenotype (e.g., tumor mutational burden [TMB] >50 mutations per megabase [mut/Mb]) recurrent or advanced metastatic colon cancer (including appendiceal adenocarcinoma), as determined by an FDA-approved test, and meet ONE of the following:

As neoadjuvant therapy for clinical T4b or bulky nodal disease (NCCN preferred)
As neoadjuvant therapy for resectable synchronous liver and/or lung metastases (if no previous treatment with a checkpoint inhibitor) (NCCN preferred)
As initial treatment for resectable metachronous metastases if no previous immunotherapy
Individual is a candidate for immunotherapy and no prior immunotherapy received in ONE of the following:

For locally unresectable or medically inoperable disease (NCCN preferred)
As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction
For synchronous unresectable metastases
As treatment for unresectable metachronous metastases

As systemic therapy for an individual with advanced or metastatic disease appendiceal adenocarcinoma who is a candidate for immunotherapy and has not received prior immunotherapy

ENDOMETRIAL CANCER

Dostarlimab-gxly (Jemperli) is considered medically necessary and, therefore, covered for the treatment of adult individuals with recurrent or advanced endometrial cancer and meet ONE of the following:

Primary treatment, in combination with carboplatin and paclitaxel (for individuals with primary advanced disease: stage IIIA, IIIB, or IIIC1 with measurable disease postsurgery, stage IIIC1 with carcinosarcoma, clear cell, serous, or mixed histology regardless of the presence of measurable disease; and stage IIIC2 or stage IV regardless of the presence of measurable disease), and dostarlimab-gxly (Jemperli) continued as a single-agent maintenance therapy (NCCN preferred) for individuals with stage III to IV endometrioid adenocarcinoma in ONE of the following scenarios:

May be considered 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 (SBRT), 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

Adjuvant treatment, in combination with carboplatin and paclitaxel (for individuals with primary advanced disease: stage IIIA, IIIB, or IIIC1 with measurable disease postsurgery; stage IIIC1 with carcinosarcoma, clear cell, serous, or mixed histology regardless of the presence of measurable disease; and stage IIIC2 or stage IV regardless of the presence of measurable disease), and dostarlimab-gxly (Jemperli) continued as a single-agent maintenance therapy (NCCN preferred), with or without EBRT and with or without vaginal brachytherapy for surgically staged individuals with stage III to IV endometrioid adenocarcinoma
First-line therapy (or second-line or subsequent therapy as clinically appropriate), in combination with carboplatin and paclitaxel (for individuals with recurrent endometrial carcinoma with or without measurable disease), and dostarlimab-gxly (Jemperli) continued as a single-agent maintenance therapy (NCCN preferred), for recurrent disease in ONE of the following scenarios:

May be considered 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 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

Used in combination with carboplatin and paclitaxel (for individuals with primary advanced endometrial carcinoma: stage IIIA, IIIB, or IIIC1 with measurable disease post-surgery; stage IIIC1 with carcinosarcoma, clear cell, serous, or mixed histology regardless of the presence of measurable disease; and stage IIIC2 or stage IV regardless of the presence of measurable disease), and dostarlimab-gxly (Jemperli) continued as a single-agent maintenance therapy (NCCN preferred), for stage III to IV tumors, including serous carcinoma, clear cell carcinoma, undifferentiated/dedifferentiated carcinoma, or carcinosarcoma in ONE of the following scenarios:

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

First-line therapy (useful in certain circumstances after prior platinum-based therapy including neoadjuvant and adjuvant), or second-line or subsequent therapy, as clinically appropriate, as a single agent for recurrent MSI-H or dMMR disease, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in ANY of the following scenarios:

May be considered 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 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

ESOPHAGEAL AND ESOPHAGOGASTRIC JUNCTION CANCERS

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with recurrent or advanced esophageal or esophagogastric junction cancer and meet ONE of the following:

As induction systemic therapy for relieving dysphagia in select individuals with MSI-H or dMMR squamous cell tumors, as determined by an FDA-approved test (independent of PD-L1 status) who are medically fit and planned for esophagectomy with cT2, N0 (high-risk lesions: lymphovascular invasion, 3 cm or greater, poorly differentiated), cT1b-cT2, N+, or cT3-cT4a, any N disease (NCCN preferred)
As palliative therapy in individuals who meet ALL of the following:

Meet ONE of the following:

Are not surgical candidates
Have unresectable locally advanced, recurrent, or metastatic disease

Karnofsky performance status (PS) 60 percent or greater or Eastern Cooperative Oncology Group (ECOG) PS 2 or less
Meet ONE of the following:

First-line (NCCN preferred) for individuals with MSI-H or dMMR squamous cell or adenocarcinoma tumors, as determined by an FDA-approved test (independent of PD-L1 status) if no prior tumor progression while on therapy with a checkpoint inhibitor
As second-line or subsequent therapy (prior use of immuno-oncology therapy will make these individuals ineligible for dostarlimab-gxly [Jemperli]) for individuals with MSI-H or dMMR squamous cell or adenocarcinoma tumors, as determined by an FDA-approved test, whose cancer is progressing on or following prior treatment and who have no satisfactory alternative treatment options if no prior tumor progression while on therapy with a checkpoint inhibitor

GASTRIC CANCER

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with dMMR or MSI-H recurrent or advanced gastric tumors, as determined by an FDA-approved test, as ONE of the following:

Primary treatment, independent of PD-L1 status, in individuals who are medically fit for surgery but with surgically unresectable locoregional disease (NCCN preferred)
Palliative therapy, independent of PD-L1 status, in individuals who meet ALL of the following:

Are not surgical candidates or have unresectable locally advanced, recurrent, or metastatic disease
Karnofsky PS 60 percent or greater or ECOG PS 2 or less
As first-line therapy (if no prior tumor progression while on therapy with a checkpoint inhibitor) (NCCN preferred)

Palliative therapy for locoregional disease in individuals who meet ALL of the following:

Are not surgical candidates or have unresectable locally advanced, recurrent, or metastatic disease (including peritoneal-only metastatic disease, including positive cytology)
Karnofsky PS 60 percent or greater or ECOG PS 2 or less
Have progressed on or following prior treatment
Have no satisfactory alternative treatment options (if no prior tumor progression while on therapy with a checkpoint inhibitor)
As second-line or subsequent therapy (prior use of immuno-oncology therapy will make these individuals ineligible for dostarlimab-gxly [Jemperli])

OCCULT PRIMARY CANCER

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with dMMR/MSI-H recurrent or advanced occult primary tumors (with adenocarcinoma or carcinoma not otherwise specified histology), as determined by an FDA-approved test, in symptomatic individuals with ECOG PS 1 to 2 or asymptomatic individuals with PS 0 and aggressive recurrent or advanced disease that have progressed on or following prior treatment and who have no satisfactory alternative treatment option for ANY of the following:

Axillary involvement in individuals with a prostate or postprostatectomy if clinically indicated
Lung nodules or breast marker–negative pleural effusion
Resectable liver disease
Peritoneal mass or ascites with nonovarian histology
Retroperitoneal mass of non–germ cell histology in selected individuals
Unresectable liver disease or disseminated metastases

OVARIAN/FALLOPIAN TUBE/PRIMARY PERITONEAL CANCER

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with recurrent or advanced dMMR or MSI-H ovarian, fallopian tube, or primary peritoneal disease, as determined by an FDA-approved test, with persistent or recurrent tumors, and meet BOTH of the following:

ONE of the following tumor histology types is present:

Endometrioid, serous
Carcinosarcoma (malignant mixed müllerian tumors)
Clear cell carcinoma
Mucinous carcinoma
Endometrioid, grade 1

ONE of the following is present:

For progression on primary, maintenance, or recurrence therapy (platinum-resistant disease)
For stable or persistent disease (if not on maintenance therapy) (platinum-resistant disease)
For complete remission and relapse less than 6 months after completing chemotherapy (platinum-resistant disease)
For radiographic and/or clinical relapse in individuals with previous complete remission and relapse 6 months or more after completing prior chemotherapy (platinum-sensitive disease)

Dostarlimab-gxly (Jemperli) is considered medically necessary and, therefore, covered for the treatment of adult individuals with dMMR or MSI-H ovarian, fallopian tube, or primary peritoneal disease (with low-grade serous, borderline epithelial histology), as determined by an FDA-approved test, in recurrent or advanced tumors as therapy for platinum-sensitive or platinum-resistance recurrence.

PANCREATIC ADENOCARCINOMA

adenosquamous and squamous histology), as determined by an FDA-approved test, with BOTH of the following:

ONE of the following scenarios:

Local recurrence in the pancreatic operative bed after resection and no prior immunotherapy
Recurrent metastatic disease with or without local recurrence after resection and no prior immunotherapy
As subsequent therapy if no prior immunotherapy for locally advanced or metastatic disease and disease progression

ONE of the following statuses:

Good ECOG PS (PS 0-1)
Intermediate ECOG PS (PS 2)

RECTAL CANCER

mut/Mb) recurrent or advanced rectal cancer, as determined by an FDA-approved test, and meet ONE of the following:

Individual is a candidate for immunotherapy and has not received prior immunotherapy as ONE of the following:

As primary treatment for synchronous abdominal/peritoneal metastases that are nonobstructing, or following local therapy for individuals with existing or imminent obstruction
As primary treatment for synchronous unresectable metastases
As primary treatment for potentially resectable or unresectable isolated pelvic/anastomotic recurrence
As primary treatment for unresectable metachronous metastases

As neoadjuvant/definitive immunotherapy (NCCN preferred) for T3, N any; T1-2, N1-2; T4, N any; or locally unresectable or medically inoperable disease (no previous treatment with a checkpoint inhibitor)
As neoadjuvant treatment for resectable synchronous liver only and/or lung only metastases (no previous treatment with a checkpoint inhibitor) (NCCN preferred)
As initial treatment for resectable metachronous metastases and no previous immunotherapy

SMALL BOWEL ADENOCARCINOMA

Dostarlimab-gxly (Jemperli), as a single agent, is considered medically necessary and, therefore, covered for the treatment of adult individuals with dMMR/MSI-H or POLE/POLD1 mutation with ultrahypermutated phenotype (e.g., TMB >50 mut/Mb) recurrent or advanced small bowel adenocarcinoma, as determined by an FDA-approved test, in ONE of the following scenarios:

As primary treatment for locally unresectable or medically inoperable disease
For any line of therapy for advanced or metastatic disease if no previous treatment with a checkpoint inhibitor

EXPERIMENTAL/INVESTIGATIONAL

All other uses of dostarlimab-gxly (Jemperli) are considered experimental/investigational and, therefore, not covered unless the indication is supported as an accepted off-label use, as defined in the 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 service.

Guidelines

There is no Medicare coverage determination addressing dostarlimab-gxly (Jemperli), therefore, the Company policy is applicable.

Certain drugs are available only through the member's medical benefit (Part B benefit), depending on how the drug is prescribed, dispensed, or administered. For Medicare Advantage members, dostarlimab-gxly (Jemperli) is covered ONLY under a member's medical benefit (Part B benefit).

BENEFIT APPLICATION

Subject to the applicable Evidence of Coverage, dostarlimab-gxly (Jemperli) is 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 KARNOFSKY PERFORMANCE STATUS

The Karnofsky Performance Status (KPS) is a standard way of measuring the ability of individuals with cancer to perform ordinary tasks. Performance scores range from 0 to 100; a higher score indicates that the individual is better able to perform activities. KPS may be used to determine an individual's prognosis, to measure changes in an individual's ability to function, or to decide if an individual can participate in a clinical trial.

The Karnofsky Performance Status Scale
100 percent	Normal, no complaints; no signs of disease
90 percent	Capable of normal activity; few symptoms or signs of disease
80 percent	Normal activity with some difficulty; some symptoms or signs of disease
70 percent	Caring for self; not capable of normal activity or work
60 percent	Requiring some help; can take care of most personal requirements
50 percent	Requires help often; requires frequent medical care
40 percent	Disabled; requires special care and help
30 percent	Severely disabled, but no risk of death
20 percent	Very ill; requires supportive measures or treatment
10 percent	Moribund; rapidly progressive fatal disease processes
0 percent	Death

OncologyPro. Performance scales: Karnofsky & ECOG scores. [OncologyPro Web site]. Available at: https://oncologypro.esmo.org/oncology-in-practice/practice-tools/performance-scales.

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 (EPS), originally published in 1982 in the American Journal of Clinical Oncology. The use of the scales and the criteria in the EPS 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
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

Dostarlimab-gxly (Jemperli) was approved by the US Food and Drug Administration (FDA) on April 22, 2021, as an accelerated approval based on tumor response rate and durability of response for the treatment of individuals with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen. Supplemental approvals for dostarlimab-gxly (Jemperli) have since been issued by the FDA.

Refer to the dostarlimab-gxly (Jemperli) prescribing information for further information on FDA-approved tests for determining mismatch repair deficiency.

PEDIATRIC USE
Dostarlimab-gxly (Jemperli) is not indicated for use in pediatric individuals less than 18 years of age.

Description

Approximately 15,000 individuals in the United States are diagnosed with either advanced or recurrent endometrial cancer (EC) annually. Some of the risk factors for EC are hormone therapy, obesity, metabolic syndrome, diabetes, family history, and certain genetic syndromes (e.g., Lynch syndrome). A common sign of EC is irregular vaginal bleeding, which usually occurs early in the cancer process, leading to a diagnosis of EC while the cancer is in an early stage. When identified in an early stage, EC can be successfully treated with either surgery alone, or in combination with radiotherapy and/or chemotherapy, which is often platinum based. If identified in later stages, or if it is recurrent or refractory to treatment, the prognosis for EC is poor. The current treatment options are limited.

There are genes within the cells of the body that correct mistakes made when the deoxyribonucleic acid (DNA) is copied. The process is called mismatch repair. Mismatch repair deficiency (dMMR) can result in errors in short, repetitive DNA sequences called microsatellites, which are genetic mutations. If a tumor has a high number of these mutations, it is classified as expressing microsatellite instability (MSI). EC tumors with dMMR and microsatellite instability-high (MSI-H) expression are difficult to treat. Based on clinical studies involving other drugs, tumors with dMMR and MSI-H respond well to anti-programmed death-1 (PD-1)-based immune checkpoint inhibitor immunotherapy.

Dostarlimab-gxly (

Jemperli) is a programmed death-1 (PD-1)-blocking immunoglobulin G4 (IgG4) humanized monoclonal antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, part of the body's immune response against foreign material, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors leading to tumor growth.

Dostarlimab-gxly (

Jemperli) binds to the PD-1 receptor on the T cells and blocks its interaction with PD-L1 and PD-L2, which allows the anti-tumor immune response to occur.

Dostarlimab-gxly (

Jemperli) was approved by the US Food and Drug Administration (FDA) on April 22, 2021, for the treatment of individuals with mismatch repair–deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.

PEER-REVIEWED LITERATURE

SUMMARY
Endometrial Cancer

Dostarlimab-gxly (Jemperli) was evaluated in the Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors (GARNET; NCT02715284), which is an ongoing multicenter, multicohort, open-label study conducted in individuals with advanced solid tumors. The efficacy population consisted of a cohort of 71 individuals with mismatch repair deficient (dMMR) recurrent or advanced EC who had progressed on or after treatment with a platinum-containing regimen. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (BICR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.

At the time of study entry, 66 percent of the individuals with dMMR EC had stage IV disease. All individuals with dMMR EC had received prior anticancer treatment, with 90 percent having received prior anticancer surgery and 79 percent having received prior anticancer radiotherapy. Approximately 40 percent had two lines or more of prior anticancer treatment, 11 percent had received three regimens, and four percent had received four or more prior regimens. The ORR was 42.3 percent with 12.7 percent achieving complete response and 29.6 percent achieving a partial response. The DOR was not reached, but 93.3 percent of individuals had a duration of response greater than or equal to 6 months. Limitations of the study included the lack of a comparator group and the small cohort size. Additional studies are currently enrolling participants.

The efficacy and safety of the use of dostarlimab-gxly (Jemperli), in combination with carboplatin and paclitaxel, was evaluated in A Study to Evaluate Dostarlimab Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Participants With Recurrent or Primary Advanced Endometrial Cancer (RUBY; NCT03981796) for the treatment of individuals with dMMR/microsatellite instability-high (MSI-H) primary advanced or recurrent endometrial cancer. The study is an ongoing phase 3, randomized, multicenter, double-blind, placebo-controlled trial with multiple arms. In this reporting, 122 individuals were randomly assigned 1:1 into two cohorts. The first cohort received dostarlimab-gxly (Jemperli), carboplatin, and paclitaxel. The second cohort received only carboplatin and paclitaxel. Treatment was continued until disease progression was identified, unacceptable toxicity was experienced by the individual, or to a maximum of 3 years (the study is continuing to 6 years). The primary outcome measures are the progression-free survival (PFS) and the overall survival (OS). Some secondary outcome measures include ORR, DOR, disease control rate (DCR), and adverse event (AE) reporting. In the combination treatment group with dostarlimab-gxly (Jemperli) (n=60), the median PFS was 30.3 months versus the median PFS in the combination treatment group without dostarlimab (Jemperli) (n=62) of 7.7 months (P<0.0001). The OS data were immature at the time of reporting. The ORR in the combination treatment group with dostarlimab-gxly (Jemperli) was 31 (11 complete responses, 20 partial responses) versus 28 (five complete responses, 23 partial responses) in the combination treatment group without dostarlimab (Jemperli). The DOR was not reached for the combination treatment group with dostarlimab-gxly (Jemperli) and was 5.4 months for the combination treatment group without dostarlimab (Jemperli).

Solid Tumors

Dostarlimab-gxly (

Jemperli) was evaluated in the GARNET study (NCT02715284), which is an ongoing, multicenter, multicohort, open-label study conducted in individuals with advanced solid tumors. The efficacy population consisted of a cohort of 209 individuals with dMMR recurrent or advanced solid tumors who had progressed following systemic therapy and had no satisfactory alternative treatment options. Individuals with dMMR colorectal cancer must have progressed after or been intolerant to a fluoropyrimidine,

oxaliplatin, and

irinotecan. The major efficacy outcome measures were ORR and DOR as assessed by BICR according to RECIST v 1.1.

At the time of study entry, 97.2 percent of individuals with nonendometrial dMMR solid tumors had stage IV disease. Approximately 43 percent of individuals had received one prior line of systemic anticancer treatment, 36 percent had received two prior lines, and 21 percent had received three or more prior lines. The ORR was 41.6 percent, with 9.1 percent achieving complete response and 32.5 percent achieving a partial response. The median DOR was 34.7 months with 95.4 percent of individuals surviving 6 months or more.

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

American Hospital Formulary Service (AHFS). Dostarlimab-gxly (Jemperli). AHFS Drug Information 2025. [

LexiComp Web site]. 02/17/2025. Available at: https://online.lexi.com/lco/action/home# [via subscription only]. Accessed February 19, 2025.

ClinicalTrials.gov. Study of TSR-042, an anti-programmed cell death-1 receptor (PD-1) monoclonal antibody, in participants with advanced solid tumors (GARNET). ClinicalTrials.gov identifier: NCT02715284. First Posted: 03/22/2016; Last Update Posted: 08/22/2023. Available at: https://clinicaltrials.gov. Accessed February 19, 2025.

Elsevier’s Clinical Pharmacology Compendium. Dostarlimab-gxly (Jemperli). [

ClinicalKey Web site]. 11/14/2024. Available at: https://www.clinicalkey.com/phamacology/ [via subscription only]. Accessed February 19, 2025.

Merative Micromedex^® DRUGDEX^® (electronic version). Dostarlimab-gxly (Jemperli). [Micromedex Web site].

Merative L.P., Ann Arbor, Michigan, USA. 01/27/2025. Available at: https://www.micromedexsolutions.com/micromedex2/librarian [via subscription only]. Accessed February 19, 2025.

Mirza MR, Chase DM,

Slomovitz BM, et al.

Dostarlimab for primary advanced or recurrent endometrial cancer. N Engl J Med. 2023;388(23):2145-2158.

National Cancer Institute. Endometrial cancer treatment. 02/12/2025. Available at: https://www.cancer.gov/types/uterine/hp/endometrial-treatment-pdq#_73. Accessed February 19, 2025.

National Cancer Institute (NCI). NCI Dictionary of Cancer Terms. Microsatellite instability-high cancer. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/microsatellite-instability-high-cancer. Accessed February 19, 2025.

National Cancer Institute (NCI). NCI Dictionary of Cancer Terms. Mismatch repair deficiency. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mismatch-repair-deficiency. Accessed February 19, 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. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Anal Carcinoma. V2.2025. [NCCN Web site]. 10/17/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/anal.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Breast Cancer. V1.2025. [NCCN Web site]. 01/31/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Colon Cancer. V1.2025. [NCCN Web site]. 02/07/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Esophageal and Esophagogastric Junction Cancers. V5.2024. [NCCN Web site]. 12/20/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Gastric Cancer. V5.2024. [NCCN Web site]. 12/20/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Occult Primary (Cancer of Unknown Primary [CUP]). V2.2025. [NCCN Web site]. 09/11/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/occult.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Ovarian Cancer Including Fallopian Tube Cancer and Primary Peritoneal Cancer. V3.2024. [NCCN Web site]. 07/15/2024. Available from: https://www.nccn.org/professionals/physician_gls/pdf/ovarian.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Pancreatic Adenocarcinoma. V2.2025. [NCCN Web site]. 02/03/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Rectal Cancer. V1.2025. [NCCN Web site]. 02/07/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Small Bowel Adenocarcinoma. V2.2025. [NCCN Web site]. 01/17/2025. Available from: https://www.nccn.org/professionals/physician_gls/pdf/small_bowel.pdf. [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology® - Uterine Neoplasms. V2.2025. [NCCN Web site]. 01/31/2025. Available at: https://www.nccn.org/professionals/physician_gls/pdf/uterine/pdf [via subscription only]. Accessed February 19, 2025.

National Comprehensive Cancer Network (NCCN). NCCN Drugs & Biologics Compendium®. Dostarlimab-gxly (Jemperli). [NCCN Web site]. 2025. Available at: https://www.nccn.org/professionals/drug_compendium/content/contents.asp [via subscription only]. Accessed February 19, 2025.

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.

Oaknin A, Tinker AV, Gilbert L, et al. Clinical activity and safety of the anti-PD-1 monoclonal antibody dostarlimab for patients with recurrent or advanced

dMMR endometrial cancer. Future Oncol. 2021;17(29):3781-3785.

Oaknin A, Tinker AV, Gilbert L, et al. Clinical activity and safety of the anti-programmed death 1 monoclonal antibody dostarlimab for patients with recurrent or advanced mismatch repair-deficient endometrial cancer: a nonrandomized phase 1 clinical trial. JAMA Oncol. 2020;6(11):1-7.

OncologyPro. Performance scales:

Karnofsky & ECOG scores. [

OncologyPro Web site]. Available at: https://oncologypro.esmo.org/oncology-in-practice/practice-tools/performance-scales. Accessed February 19, 2025.

Overman MJ, Morse M. Overview of advanced

unresectable and metastatic solid tumors with DNA mismatch repair deficiency or high tumor mutational burden. [UpToDate Web Site]. Updated 08/16/2024. Available at: https://www.uptodate.com/contents/overview-of-advanced-unresectable-and-metastatic-solid-tumors-with-dna-mismatch-repair-deficiency-or-high-tumor-mutational-burden?search=Tissue-agnostic cancer therapy: DNA mismatch repair deficiency, tumor mutational burden, and response to immune checkpoint blockade in solid

tumors&source=

search_result&selectedTitle=1~150&usage_type=

default&display_rank=1. [via subscription only]. Accessed February 19, 2025.

Patnaik A, Weiss GJ,

Rasco DW, et al. Safety, antitumor activity, and pharmacokinetics of dostarlimab, an anti-PD-1, in patients with advanced solid tumors: a dose-escalation phase 1 trial. Cancer Chemother Pharmacol. 2022;89(1):93-103.

UpToDate^®

Lexidrug^TM. Dostarlimab-gxly (Jemperli). [UpToDate Lexidrug Web site]. 02/07/2025. Available at: https://online.lexi.com/lco/action/home

[via subscription only]. Accessed February 19, 2025.

US Food and Drug Administration (FDA). Center for Drug Evaluation and Research. Dostarlimab-gxly (Jemperli) prescribing information and approval letter. [FDA Web site]. 08/01/2024. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed February 19, 2025.

US Food and Drug Administration (FDA). List of cleared or approved companion diagnostic devices (in vitro and imaging tools). 01/28/2025. Available at: https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools. Accessed February 19, 2025.

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)

J9272 Injection, dostarlimab-gxly, 10 mg

Revenue Code Number(s)

N/A

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History

Revisions From MA08.136f:

05/19/2025

This version of the policy will become effective 05/19/2025.

The following indication has been added to this policy in accordance with the National Comprehensive Cancer Network (NCCN) compendium (accessed 02/19/2025) and the following NCCN guideline:
Anal carcinoma V2.2025 (01/17/2025)

The following policy criteria have been revised in accordance with the NCCN compendium and the following NCCN guidelines:
Colon cancer V1.2025 (02/07/2025)
Esophageal and esophagogastric junction cancers V5.2024 (12/20/2024)
Gastric cancer V5.2024 (12/20/2024)
Pancreatic adenocarcinoma V2.2025 (02/03/2025)
Rectal cancer V1.2025 (02/07/2025)
Small bowel adenocarcinoma V2.2025 (01/17/2025)
Uterine neoplasms V2.2025 (01/31/2025)

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

Revisions From MA08.136e:

03/11/2024

This version of the policy will become effective 03/11/2024.

The following policy criterion has been added to this policy in accordance with the National Comprehensive Cancer Network (NCCN) compendium (accessed 01/17/2024) and the following NCCN guideline:
Pancreatic adenocarcinoma V1.2024 (12/13/2023)

The following policy criteria have been revised in accordance with the NCCN compendium and the following NCCN guidelines:
Ampullary adenocarcinoma V1.2024 (12/13/2023)
Breast cancer V5.2023 (12/05/2023)
Colon cancer V4.2023 (11/16/2023)
Esophageal and esophagogastric junction cancers V3.2023 (08/29/2023)
Gastric cancer V2.2023 (08/29/2023)
Occult primary V1.2024 (09/06/2023)
Ovarian/fallopian tube/primary peritoneal cancer V2.2023 (06/02/2023)
Rectal cancer V6.2023 (11/16/2023)
Small bowell adenocarcinoma V1.2024 (12/20/2023)
Uterine neoplasms V1.2024 (09/20/2023)

The following ICD-10 codes have been added to the policy:
C15.3, C15.4, C15.5, C15.8, C15.9, C25.0, C25.1, C25.2, C25.3, C25.7, C25.8, C25.9, D37.8, D37.9.

Revisions From MA08.136d:

01/01/2024	Effective 01/01/2024 this policy applies to New Jersey Medicare Advantage (MA) lines of business.
03/13/2023	This version of the policy will become effective 03/13/2023 The following policy criteria have been added to this policy in accordance with the National Comprehensive Cancer Network (NCCN) compendium (accessed 12/27/2022) and the following NCCN guidelines: Ampullary adenocarcinoma (NCCN V2.2022; 12/06/2022) Esophageal and esophagogastric junction cancers (NCCN V5.2022; 12/05/2022) The following policy criteria have been revised in accordance with the NCCN compendium and the following NCCN guidelines: Colon cancer (including appendiceal adenocarcinoma) (NCCN V2.2022; 10/27/2022) Gastric cancer (NCCN V2.2022; 01/11/2022) Occult primary cancer (NCCN V3.2023; 12/21/2022) Ovarian/fallopian tube/primary peritoneal cancer (NCCN V1.2023; 12/22/2022) Small bowel adenocarcinoma (NCCN V2.2022; 10/27/2022) Uterine neoplasms (NCCN V1.2023; 12/22/2022) The following ICD-10 codes have been removed from the policy: C50.019, C50.029, C50.119, C50.129, C50.219, C50.229, C50.319, C50.329, C50.419, C50.429, C50.519, C50.529, C50.619, C50.629, C50.819, C50.829, C50.919, C50.929, C56.9, C57.00, C57.10, C57.20, C78.00

01/01/2024

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

03/13/2023

This version of the policy will become effective 03/13/2023

The following policy criteria have been added to this policy in accordance with the National Comprehensive Cancer Network (NCCN) compendium (accessed 12/27/2022) and the following NCCN guidelines:
Ampullary adenocarcinoma (NCCN V2.2022; 12/06/2022)
Esophageal and esophagogastric junction cancers (NCCN V5.2022; 12/05/2022)

The following policy criteria have been revised in accordance with the NCCN compendium and the following NCCN guidelines:
Colon cancer (including appendiceal adenocarcinoma) (NCCN V2.2022; 10/27/2022)
Gastric cancer (NCCN V2.2022; 01/11/2022)
Occult primary cancer (NCCN V3.2023; 12/21/2022)
Ovarian/fallopian tube/primary peritoneal cancer (NCCN V1.2023; 12/22/2022)
Small bowel adenocarcinoma (NCCN V2.2022; 10/27/2022)
Uterine neoplasms (NCCN V1.2023; 12/22/2022)

The following ICD-10 codes have been removed from the policy:
C50.019, C50.029, C50.119, C50.129, C50.219, C50.229, C50.319, C50.329, C50.419, C50.429, C50.519, C50.529, C50.619, C50.629, C50.819, C50.829, C50.919, C50.929, C56.9, C57.00, C57.10, C57.20, C78.00

Revisions From MA08.136c:

03/28/2022

This version of the policy will become effective 03/28/2022.

The following policy criteria have been added to this policy:
Medically necessary criteria for Solid Tumor cancer in accordance with the US Food and Drug Administration (FDA) label (08/17/2021) and the National Comprehensive Cancer Network (NCCN) compendium (accessed 12/15/2021)

Breast cancer (NCCN V1.2022; 11/24/2021)
Colon cancer (NCCN V3.2021; 09/10/2021)
Gastric cancer (NCCN V5.2021; 10/06/2021)
Occult primary cancer (Cancer of Unknown Primary [CUP]) (NCCN V1.2022; 09/02/2021)
Ovarian/Fallopian tube/Primary peritoneal cancer (NCCN V3.2021; 09/09/2021)
Rectal cancer (NCCN V2.2021; 09/10/2021)
Small bowel adenocarcinoma (NCCN V1.2022; 09/10/2021)
Peer-reviewed literature

The following ICD-10 codes have been added to this policy:
C16.0, C16.1, C16.2, C16.3, C16.4, C16.5, C16.6, C16.8, C16.9, C17.0, C17.1, C17.2, C17.3, C17.8, C17.9, C18.0, C18.1, C18.2, C18.3, C18.4, C18.5, C18.6, C18.7, C18.8, C18.9, C19, C20, C21.0, C21.1, C21.2, C21.8, C24.1, C48.1, C48.2, C48.8, C50.011, C50.012, C50.019, C50.021, C50.022, C50.029, C50.111, C50.112, C50.119, C50.121, C50.122, C50.129, C50.211, C50.212, C50.219, C50.221, C50.222, C50.229, C50.311, C50.312, C50.319, C50.321, C50.322, C50.329, C50.411, C50.412, C50.419, C50.421, C50.422, C50.429, C50.511, C50.512, C50.519, C50.521, C50.522, C50.529, C50.611, C50.612, C50.619, C50.621, C50.622, C50.629, C50.811, C50.812, C50.819, C50.821, C50.822, C50.829, C50.911, C50.912, C50.919, C50.921, C50.922, C50.929, C54.0, C54.2, C54.3, C54.8, C54.9, C55, C56.1, C56.2, C56.3, C56.9, C57.00, C57.01, C57.02, C57.10, C57.11, C57.12, C57.20, C57.21, C57.22, C57.3, C57.4, C57.7, C57.8, C57.9, C78.00, C78.01, C78.02, C78.6, C78.7, C80.0, C80.1, D07.0, D37.1

The following policy criteria have been revised:
Endometrial cancer (NCCN V1.2022; 11/04/2021)

Revisions From MA08.136b:

01/01/2022

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

Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS code has been deleted from this policy:
C9082: Injection, dostarlimab-gxly, 100 mg

The following HCPCS code has been added to this policy:

J9272: Injection, dostarlimab-gxly, 10 mg

Revisions From MA08.136a:

10/01/2021

This version of the policy will become effective 10/01/2021

Inclusion of a policy in a Code Update memo does not imply that a full review of
the policy was completed at this time.

The following HCPCS code has been deleted from this policy:
C9399: Unclassified drug or biological

The following HCPCS code has been added to this policy:

C9082: Injection, dostarlimab-gxly, 100 mg

Revisions From MA08.136:

07/12/2021

The following new policy has been developed to communicate the Company’s coverage criteria for dostarlimab-gxly (Jemperli) in accordance with the US Food and Drug Administration (04/22/2021).

Version Effective Date:

5/19/2025

Version Issued Date:

5/19/2025

Version Reissued Date:

Medicare Advantage

Medical Policy

Notification

Policy

Guidelines

Description

References

Coding

CPT Procedure Code Number(s)

ICD - 10 Procedure Code Number(s)

ICD - 10 Diagnosis Code Number(s)

HCPCS Level II Code Number(s)

Revenue Code Number(s)

MPMiscCodesNarrativesPub

Coding and Billing Requirements

Cross Reference

Policy History