Dostarlimab-gxly (Jemperli)

Number: 0993

Table Of Contents

Policy
Applicable CPT / HCPCS / ICD-10 Codes
Background
References

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Policy

Scope of Policy

This Clinical Policy Bulletin addresses dostarlimab-gxly (Jemperli) for commercial medical plans. For Medicare criteria, see Medicare Part B Criteria.

Note: Requires Precertification:

Precertification of dostarlimab-gxly (Jemperli) is required of all Aetna participating providers and members in applicable plan designs. For precertification of dostarlimab-gxly (Jemperli), call (866) 752-7021 or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification. 

Note: Site of Care Utilization Management Policy applies.  For information on site of service for dostarlimab-gxly (Jemperli), see Utilization Management Policy on Site of Care for Specialty Drug Infusions. 

1. Exclusions

   Aetna will not provide coverage for members who have experienced disease progression while on PD-1 or PD-L1 inhibitor therapy.

2. Criteria for Initial Approval

   1. Ampullary Adenocarcinoma

      Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for subsequent treatment of recurrent or advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) ampullary adenocarcinoma that has progressed on or following prior treatment and has no satisfactory alternative treatment options.

   2. Endometrial Carcinoma

      1. Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of recurrent or advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen.
      2. Aetna considers dostarlimab-gxly (Jemperli) medically necessary for primary or adjuvant treatment of endometrial carcinoma in combination with carboplatin and paclitaxel (for up to 6 doses of combination therapy followed by Jemperli monotherapy) in members with stage III-IV or recurrent disease.

   3. Solid Tumors

      Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of mismatch repair deficient (dMMR) solid tumors in members with recurrent or advanced disease that have progressed on or following prior treatment and for whom there are no satisfactory alternative treatment options.

   4. Breast Cancer

      Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent in members with no response to preoperative systemic therapy, recurrent unresectable or stage IV breast cancer, that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and has progressed on or following prior treatment and has no satisfactory alternative treatment options.

   5. Colorectal Cancer

      Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of advanced or metastatic colorectal cancer, including appendiceal adenocarcinoma and anal adenocarcinoma, that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR).

   6. Esophageal, Esophagogastric Junction and Gastric Cancer

      1. Aetna considers dostarlimab-gxly (Jemperli) medically necessary for treatment of esophageal cancer, esophagogastric junction cancer, or gastric adenocarcinoma when all of the following criteria are met:

         1. The requested medication will be used as a single agent; and
         2. The requested medication will be used as palliative therapy for patients who are not surgical candidates or have unresectable locally advanced, recurrent, or metastatic disease; and 
         3. The requested medication will be used for microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors; and
         4. The requested medication will be used in patients whose cancer is progressing on or following prior treatment and who have no satisfactory alternative treatment options.

      2. Aetna considers dostarlimab-gxly (Jemperli) medically necessary for treatment of gastric adenocarcinoma if tumor is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) in members who are medically fit for surgery with surgically unresectable locoregional disease.

   7. Occult Primary Cancer

      Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of occult primary cancer that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) and has progressed on or following prior treatment and has no satisfactory alternative treatment options.

   8. Ovarian Cancer

      Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of epithelial ovarian cancer, fallopian tube cancer, primary peritoneal cancer, carcinosarcoma (malignant mixed Mullerian tumors), clear cell carcinoma of the ovary, mucinous carcinoma of the ovary, grade 1 endometrioid carcinoma, and low-grade serous carcinoma/ovarian borderline epithelial tumors for recurrent, persistent, or advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors.

   9. Pancreatic Adenocarcinoma

      Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of recurrent, locally advanced, metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) pancreatic adenocarcinoma when member has ECOG 0-2.

   10. Small Bowel Adenocarcinoma

       Aetna considers dostarlimab-gxly (Jemperli) medically necessary as a single agent for treatment of advanced or metastatic small bowel adenocarcinoma for microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors.

   Aetna considers all other indications as experimental and investigational (for additional information, see Experimental and Investigational and Background sections).

3. Continuation of Therapy

   1. Endometrial Carcinoma when used as combination therapy

      Aetna considers continuation of dostarlimab-gxly (Jemperli) therapy (up to 36 months total) medically necessary in members requesting reauthorization for endometrial cancer when the requested medication is being used in combination therapy regimen and there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

   2. All Other Indications

      Aetna considers continuation of dostarlimab-gxly (Jemperli) therapy medically necessary in members requesting reauthorization for an indication listed in Section II when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Dostarlimab-gxly is supplied as Jemperli 500 mg/10 mL (50 mg/mL) solution in a single-dose vial for intravenous infusion.

The recommended dosage of Jemperli is as follows:

• In combination with carboplatin and paclitaxel, for dMMR or diarrhea, and nausea. Most common Grade 3 or 4 laboratory MSI-H primary advanced or recurrent endometrial cancer: 500 mg every 3 weeks for 6 doses followed by 1,000 mg monotherapy every 6 weeks.
• As a single-agent, for dMMR recurrent or advanced endometrial cancer: 500 mg every 3 weeks for 4 doses followed by 1,000 mg every 6 weeks.
• As a single-agent, for dMMR recurrent or advanced solid tumors: 500 mg every 3 weeks for 4 doses followed by 1,000 mg every 6 weeks.
• Administer as an intravenous infusion over 30 minutes.
• Refer to full prescribing information for complete dosing instructions.

Source: GlaxoSmithKline, 2023

Experimental and Investigational

Aetna considers combined niraparib and dostarlimab experimental and investiagtional for recurrent endometrial carcinoma.

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Table:

CPT Codes / HCPCS Codes / ICD-10 Codes

Code	Code Description
Other CPT codes related to the CPB:
96413 - 96417	Chemotherapy administration
HCPCS codes covered if selection criteria are met:
J9272	Injection, dostarlimab-gxly, 10 mg
Other HCPCS codes related to the CPB:
Niraparib - no specific code
J9045	Injection, carboplatin, 50 mg
J9267	Injection, paclitaxel, 1 mg
ICD-10 codes covered if selection criteria are met:
C11.0 - C11.9	Malignant neoplasm of nasopharynx [mismatch repair deficient (dMMR) recurrent or advanced]
C12	Malignant neoplasm of pyriform sinus [mismatch repair deficient (dMMR) recurrent or advanced]
C13.0 - C13.9	Malignant neoplasm of hypopharynx [mismatch repair deficient (dMMR) recurrent or advanced]
C14.0 - C14.8	Malignant neoplasm of other and ill-defined sites in the lip, oral cavity and pharynx [mismatch repair deficient (dMMR) recurrent or advanced]
C15.3 - C15.9	Malignant neoplasm of esophagus [mismatch repair deficient (dMMR) recurrent or advanced]
C16.0 - C16.9	Malignant neoplasm of stomach [mismatch repair deficient (dMMR) recurrent or advanced]
C17.0 - C17.9	Malignant neoplasm of small intestine [mismatch repair deficient (dMMR) recurrent or advanced]
C18.0 - C18.9	Malignant neoplasm of colon [mismatch repair deficient (dMMR) recurrent or advanced]
C19 - C21.8	Malignant neoplasm of rectosigmoid junction, rectum, anus and anal canal [mismatch repair deficient (dMMR) recurrent or advanced]
C22.0	Liver cell carcinoma [mismatch repair deficient (dMMR) recurrent or advanced]
C22.1	Intrahepatic bile duct carcinoma [mismatch repair deficient (dMMR) recurrent or advanced]
C23 - C24.9	Malignant neoplasm of gall bladder and other and unspecified parts of biliary tract [mismatch repair deficient (dMMR) recurrent or advanced]
C25.0 - C25.9	Malignant neoplasm of pancreas [mismatch repair deficient (dMMR) recurrent or advanced, metastatic, microsatellite instability-high (MSI-H)]
C26.0 - C26.9	Malignant neoplasm of other and ill-defined digestive organs [mismatch repair deficient (dMMR) recurrent or advanced]
C30.0 - C30.1	Malignant neoplasm of nasal cavity and middle ear [mismatch repair deficient (dMMR) recurrent or advanced]
C31.0 - C31.9	Malignant neoplasm of accessory sinuses (paranasal) [mismatch repair deficient (dMMR) recurrent or advanced]
C33	Malignant neoplasm of trachea [mismatch repair deficient (dMMR) recurrent or advanced]
C34.00 - C34.92	Malignant neoplasm of bronchus and lung [mismatch repair deficient (dMMR) recurrent or advanced]
C37	Malignant neoplasm of thymus [mismatch repair deficient (dMMR) recurrent or advanced]
C38.0 - C38.8	Malignant neoplasm of heart, mediastinum and pleura [mismatch repair deficient (dMMR) recurrent or advanced]
C39.0 - C39.9	Malignant neoplasm of other and ill-defined sites in the respiratory system and intrathoracic organs [mismatch repair deficient (dMMR) recurrent or advanced]
C40.00 - C40.92	Malignant neoplasm of bone and articular cartilage of limbs [mismatch repair deficient (dMMR) recurrent or advanced]
C41.0 - C41.9	Malignant neoplasm of bone and articular cartilage of other and unspecified sites [mismatch repair deficient (dMMR) recurrent or advanced]
C43.0 - C43.9	Malignant melanoma of skin [mismatch repair deficient (dMMR) recurrent or advanced]
C44.00 - C44.201	Other and unspecified malignant neoplasm of skin [mismatch repair deficient (dMMR) recurrent or advanced]
C46.1	Kaposi's sarcoma of soft tissue [mismatch repair deficient (dMMR) recurrent or advanced]
C47.0 - C47.9	Malignant neoplasm of peripheral nerves and autonomic nervous system [mismatch repair deficient (dMMR) recurrent or advanced]
C48.0 - C48.8	Malignant neoplasm of retroperitoneum and peritoneum [mismatch repair deficient (dMMR) recurrent or advanced]
C49.0 - C49.9	Malignant neoplasm of other connective and soft tissue [mismatch repair deficient (dMMR) recurrent or advanced]
C50.011 - C50.929	Malignant neoplasm of female and male breast [mismatch repair deficient (dMMR) recurrent or advanced]
C51.0 - C51.9	Malignant neoplasm of vulva [mismatch repair deficient (dMMR) recurrent or advanced]
C52	Malignant neoplasm of vagina [mismatch repair deficient (dMMR) recurrent or advanced]
C53.0 - C53.9	Malignant neoplasm of cervix uteri [mismatch repair deficient (dMMR) recurrent or advanced]
C54.0 - C54.9	Malignant neoplasm of corpus uteri [mismatch repair deficient (dMMR) recurrent or advanced]
C55	Malignant neoplasm of uterus, part unspecified [mismatch repair deficient (dMMR) recurrent or advanced]
C56.1 - C56.9	Malignant neoplasm of ovary [mismatch repair deficient (dMMR) recurrent or advanced]
C57.00 - C57.02	Malignant neoplasm of fallopian tube [mismatch repair deficient (dMMR) recurrent or advanced]
C58	Malignant neoplasm of placenta [mismatch repair deficient (dMMR) recurrent or advanced]
C60.0 - C60.9	Malignant neoplasm of penis [mismatch repair deficient (dMMR) recurrent or advanced]
C61	Malignant neoplasm of prostate [mismatch repair deficient (dMMR) recurrent or advanced]
C62.00 - C62.92	Malignant neoplasm of testis [mismatch repair deficient (dMMR) recurrent or advanced]
C63.00 - C63.9	Malignant neoplasm of other and unspecified male genital organs [mismatch repair deficient (dMMR) recurrent or advanced]
C64.1 - C68.9	Malignant neoplasm of kidney and other and unspecified urinary organs [mismatch repair deficient (dMMR) recurrent or advanced]
C69.00 - C69.92	Malignant neoplasm of eye and adnexa [mismatch repair deficient (dMMR) recurrent or advanced]
C70.0 - C70.9	Malignant neoplasm of meninges [mismatch repair deficient (dMMR) recurrent or advanced]
C71.0 - C71.9	Malignant neoplasm of brain [mismatch repair deficient (dMMR) recurrent or advanced]
C72.0 - C72.9	Malignant neoplasm of spinal cord, cranial nerves and other parts of central nervous system [mismatch repair deficient (dMMR) recurrent or advanced]
C73	Malignant neoplasm of thyroid gland [mismatch repair deficient (dMMR) recurrent or advanced]
C7A.1 - C7A.8	Malignant poorly differentiated neuroendocrine tumors [mismatch repair deficient (dMMR) recurrent or advanced]
C80.0 - C80.1	Malignant neoplasm without specification of site [mismatch repair deficient (dMMR) recurrent or advanced]
D00.00 - D09.9	Carcinoma in situ [mismatch repair deficient (dMMR) recurrent or advanced]

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Background

U.S. Food and Drug Administration (FDA)-Approved Indications 

• Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H).
• Jemperli is indicated as a single agent for the treatment of adult patients with dMMR recurrent or advanced endometrial cancer (EC), as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation.
• Jemperli is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

Compendial Uses

• Breast cancer
• Colorectal cancer
• Esophageal and esophagogastric junction cancers
• Gastric cancer
• Occult primary cancer
• Ovarian cancer
  
  
  • Epithelial ovarian cancer
  • Fallopian tube cancer
  • Primary peritoneal cancer
  • Carcinosarcoma (malignant mixed Mullerian tumors)
  • Clear cell carcinoma of the ovary
  • Mucinous carcinoma of the ovary
  • Grade 1 endometrioid carcinoma
  • Low-grade serous carcinoma/ovarian borderline epithelial tumors
    
    
• Endometrial carcinoma
• Small bowel adenocarcinoma
• Ampullary adenocarcinoma
• Pancreatic adenocarcinoma

Dostarlimab-gxly is available as Jemperli (GlaxoSmithKline) and is a programmed death receptor-1 (PD-1)-blocking lgG4 humanized monoclonal antibody. By binding PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor located on T cells, T-cell proliferation and cytokine production are inhibited (GlaxoSmithKline, 2021a).

Per the prescribing information, dostarlimab-gxly (Jemperli) carries the following warnings and precautions:

• Immune-mediated adverse reactions, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis, and immune-mediated dermatologic adverse reactions;
• Infusion-related reactions;
• Complications of allogeneic HSCT after PD-1/L-1–blocking antibody;
• Embryo-fetal toxicity.

The most common adverse reactions (≥20%) are fatigue/asthenia, nausea, diarrhea, anemia, and constipation (GlaxoSmithKline, 2021a).

Endometrial Cancer

In the U.S., endometrial cancer (EC) is the most frequent gynecological malignancy with its prevalence on the rise. An estimated 75% of endometrial cancers are diagnosed at the beginning stage and are usually curable with surgery. Nevertheless, there are limited treatment options beyond front-line standard therapy with a platinum-containing chemotherapeutic regimen for women with advanced and recurrent endometrial cancer. Additionally, an estimated 25% to 30% of advanced endometrial cancer patients have mismatch repair deficient (dMMR) tumors (FDA, 2021a).

On April 22, 2021, the U.S. Food and Drug Administration (FDA) approved Jemperli (dostarlimab-gxly), a programmed death receptor-1 (PD-1) blocking antibody, indicated for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced endometrial cancer, as confirmed by an FDA-approved test, that have progressed on or following prior treatment with a platinum-containing regimen (GlaxoSmithKline, 2021a). The FDA granted Priority Review designation and Breakthrough Therapy designation to Jemperli for the endometrial cancer indication using the Accelerated Approval pathway (FDA, 2021a). The approval was based on supporting data from the ongoing GARNET study.

In the GARNET study, a multi-center, multicohort, open-label, non-randomized Phase 1 trial, Oaknin and colleagues (2020) evaluated the efficacy and safety of Jemperli in patients with dMMR endometrial cancer. Of the 104 enrolled women patients, the efficacy population consisted of 71 patients with dMMR recurrent or advanced EC who progressed on or after treatment with a platinum-containing regimen. Patients received 500 mg of Jemperli intravenously every 3 weeks for 4 doses followed by 1000 mg every 6 weeks until disease progression, treatment discontinuation, or withdrawal. The primary endpoints included objective response rate (ORR) and duration of response (DOR). Confirmed response was noted in 30 patients (objective response rate, 42.3%; 95% confidence interval [CI], 30.6%-54.6%); 9 patients (12.7%) had a confirmed complete response, and 21 patients (29.6%) had a confirmed partial response. The median duration of response was not reached (median follow-up was 11.2 months).The safety profile for Jemperli in patients included the occurrence of anemia (3 of 104 [2.9%]), colitis (2 of 104 [1.9%]), and diarrhea (2 of 104 [1.9%]) being the most common grade 3 or higher treatment-related adverse events.

On February 9, 2023, the U.S. Food and Drug Administration (FDA) approved dostarlimab-gxly (Jemperli) for adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, which has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Efficacy for the regular approval was evaluated in the GARNET study which consisted of a cohort of 141 patients with dMMR recurrent or advanced endometrial cancer who had progressed on or after a platinum-containing regimen. Patients were excluded due to the following: treatment with prior PD-1/PD-L1-blocking antibodies, other immune checkpoint inhibitors, or if they had autoimmune diseases requiring systemic immunosuppressant agents within 2 years. The primary efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). Confirmed ORR was 45.4% (95% CI: 37.0, 54.0), with a 15.6% complete response rate and a 29.8% partial response rate. Median DOR was not reached, with 85.9% of patients having durations ≥12 months and 54.7% of patients having durations ≥24 months (range: 1.2+, 52.8+) (FDA, 2023b; GlaxoSmithKline, 2023).

On July 31, 2023, the U.S. Food and Drug Administration (FDA) approved dostarlimab-gxly (Jemperli) with carboplatin and paclitaxel, followed by single-agent Jemperli, for primary advanced or recurrent endometrial cancer (EC) that is mismatch repair deficient (dMMR), as determined by an FDA-approved test, or microsatellite instability-high (MSI-H). Efficacy was evaluated in RUBY, a randomized, multicenter, double-blind, placebo-controlled trial. The investigators performed an efficacy assessment in a pre-specified subgroup of 122 patients with dMMR/MSI-H primary advanced or recurrent EC. MMR/MSI tumor status was determined by local testing assays (IHC, PCR, or NGS), or central testing (IHC), using the Ventana MMR RxDx Panel, when local results were unavailable. Patient randomization (1:1) was to either Jemperli with carboplatin and paclitaxel, followed by Jemperli, or placebo with carboplatin and paclitaxel, followed by placebo. Randomization was stratified by MMR/MSI status, prior external pelvic radiotherapy, and disease status (recurrent, primary Stage III, or primary Stage IV). The primary efficacy outcome measure was investigator-assessed progression-free survival (PFS) using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). Additional efficacy outcome measures included overall survival (OS), objective response rate (ORR), and duration of response (DOR). A statistically significant PFS improvement was observed in the dMMR/MSI-H population with a median PFS of 30.3 versus 7.7 months (Hazard Ratio=0.29 [95% CI: 0.17, 0.50]; p<0.0001), for the dostarlimab-gxly and placebo-containing regimens, respectively (FDA, 2023a; GlaxoSmithKline, 2023).

Combined Niraparib and Dostarlimab for the Treatment of Recurrent Endometrial Carcinoma

In a non-randomized, open-label, multi-center, pilot, phase-II clinical trial, Madariaga et al (2023) examined niraparib monotherapy (cohort 1, C1), or niraparib and dostarlimab (cohort 2, C2) in patients with recurrent serous or endometrioid endometrial carcinoma. The primary endpoint was clinical benefit rate (CBR), with greater than or equal to 5/22 overall considered of interest. Secondary outcomes were safety, ORR, duration of response, PFS and overall survival (OS). Translational research was an exploratory outcome. Potential biomarkers were evaluated in archival tissue by immunohistochemistry (IHC) and next generation sequencing (NGS) panel. In C1, 25 patients were enrolled, and CBR was 20 % (95 % CI: 9 to 39) with median clinical benefit duration of 5.3 months. The ORR was 4 % (95 % CI: 0 to 20). In C2, 22 patients were enrolled, and the CBR was 31.8 % (95 % CI: 16 to 53) with median clinical benefit duration of 6.8 months. The ORR was 14 % (95 % CI: 3 to 35). No new safety signals were detected. No significant association was detected between clinical benefit and IHC markers (PTEN, p53, MMR, PD-L1), or molecular profiling (PTEN, TP53, homologous recombination repair genes). The authors concluded that niraparib monotherapy did not meet the effectiveness threshold; combined niraparib and dostarlimab showed modest activity. Moreover, these researchers stated that one of the limitations of the study was its heterogeneous population, in terms of histological, molecular characteristics and platinum sensitivity. In this pilot study, a predominantly platinum-resistant population was included.

Dostarlimab for the Treatment of Cervical Cancer

Garcia-Duran et al (2022) stated that currently, women diagnosed with high-risk locally advanced cervical cancer are at high risk of recurrence following treatment with concurrent chemo-radiation and represent a population with high unmet need. The ATOMICC Trial is a randomized, open-label, multi-center, phase-II clinical trial. The primary objective of this trial is to examine the progression-free survival (PFS) of high-risk locally advanced cervical cancer patients who have achieved a partial or complete response (PR or CR) after chemo-radiation after receiving dostarlimab as maintenance therapy. The control arm entails a clinical and radiological follow-up, with no further treatment (current standard of care [SOC]). The ATOMICC Trial is an investigator-driven trial sponsored by GEICO (Grupo Español de Investigación en Cáncer de Ovario) and supported by GlaxoSmithKline (GSK). Women aged over 18 years with a biopsy-confirmed squamous cell carcinoma, adenocarcinoma, or adeno-squamous carcinoma of the cervix meeting the following staging criteria: International Federation of Gynecology and Obstetrics (FIGO) 2009 stages of IB2, IIA2, IIB with pelvic lymph node involvement, FIGO stages IIIA, IIIB, IVA, and any FIGO 2009 stage with para-aortic lymph node involvement are eligible for the Trial. All participants must have achieved a PR or CR after definitive concurrent chemo-radiation. Women diagnosed with FIGO stage IVB, having undergone a previous hysterectomy, or having a history of active autoimmune disease will not be considered eligible. Primary endpoint is PFS defined as the time from the date of randomization to the date of 1st disease progression or death due to any cause, whichever occurs first. A total of 132 participants are expected to be recruited in the study, using a 1:2 (control:experimental arm) randomization allocation ratio. The Trial was launched in the 2nd quarter of 2019; it is estimated to be closed for recruitment in the 3rd quarter of 2022. Results are expected to be released in the 3rd quarter of 2024.

Dostarlimab for the Treatment of Recurrent/Advanced Non-Small Cell Lung Cancer

Moreno et al (2022) noted that dostarlimab is an anti-PD-1 antibody being studied in recurrent/advanced solid tumors, including non-small cell lung cancer (NSCLC), in the ongoing phase-I, open-label, multi-center, 2-part (dose escalation and cohort expansion) GARNET study. These investigators reported an interim analysis of patients with recurrent/advanced NSCLC who progressed following platinum-based chemotherapy. Patients received dostarlimab (500 mg IV every 3 weeks [Q3W] for Cycles 1 to 4, then 1,000 mg Q6W) until disease progression or unacceptable toxicity for more than 2 years. The primary endpoints were immune-related ORR (irORR) per investigator-assessed irRECIST and safety. As of July 8, 2019, a total of 67 patients with recurrent/advanced NSCLC were enrolled and treated with dostarlimab; the majority had PD-L1 tumor proportion score (TPS) of less than 1 % (35.8 % of patients) or PD-L1 TPS 1 % to 49 % (29.9 % of patients); 7.5 % had PD-L1 TPS of 50 % or higher, and 26.9 % had unknown PD-L1 TPS status. Median follow-up was 13.8 months (range of 0.0 to 22.6 months). irORR was 26.9 %, including 2 CRs and 16 PRs. The median duration of response of 11.6 months (range of 2.8 to 19.4). Responses were observed in 2 of 24 (16.7 %) patients with PD-L1 TPS of less than 1 %, 4 of 20 (20.0 %) patients with PD-L1 TPS 1 % to 49 % and 2 of 5 (40.0 %) patients with PD-L1 TPS of 50 % or higher. Fatigue (4.5 %) was the most common grade-3 or higher treatment-related treatment-emergent adverse event (TRAE). Immune-related TRAEs (any grade) were observed in 28.4 % of patients. The authors concluded that dostarlimab showed promising anti-tumor activity in advanced/recurrent NSCLC that progressed following platinum-based chemotherapy, including across all PD-L1 subgroups, and has an acceptable safety profile.

Solid Tumors

On August 17, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Jemperli (dostarlimab-gxly) for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The approval was based on supporting data from the non-randomized, multicenter, open-label, multi-cohort GARNET study (FDA, 2021b).

In the GARNET study, the efficacy population comprised 209 patients with dMMR recurrent or advanced solid tumors who progressed following systemic therapy and had no satisfactory alternative treatment. Patients received Jemperli 500mg intravenously every 3 weeks for 4 doses followed by 1,000 mg intravenously every 6 weeks until disease progression or unacceptable toxicity. Primary efficacy endpoints included overall response rate (ORR) and duration of response (DOR). The results were as follows:41.6% (95% CI: 34.9, 48.6) for ORR, 9.1% for complete response rate, 32.5% for partial response rate, and 34.7 months (range 2.6, 35.8+) median DOR with 95.4% of patients with duration ≥ 6 months. The most common adverse reactions (≥20%) in these patients included fatigue/asthenia, anemia, diarrhea, and nausea. Commonly occurring Grade 3 or 4 reactions (≥2%) included anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury (FDA, 2021b).

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References