Dostarlimab Wins Full Approval in Canada for dMMR/MSI-H Endometrial Cancer

Health Canada has granted full approval to dostarlimab-gxly (Jemperli) monotherapy for adult patients with recurrent or advanced mismatch repair­–deficient (dMMR) or microsatellite instability–high (MSI-H) endometrial cancer who have progressed on or after treatment with a platinum-based regimen.¹

The agent had previously received a Notice of Compliance with conditions (NOC/c) for this patient population from Health Canada in December 2021. The conversion of this indication to full approval was supported by additional data from the A1 expansion cohort of the phase 1 GARNET trial (NCT02715284). Long-term findings demonstrated a confirmed objective response rate (ORR) of 45.5% (95% CI, 37.1%-54.0%) in patients with dMMR/MSI-H endometrial cancer. At a median follow-up of 27.6 months, the median duration of response (DOR) was not reached (range, 1.18+, 47.21+ months) .

“We remain committed to exploring the full potential of dostarlimab as the foundation of our immuno-oncology portfolio, aiming to meet the needs of patients in various stages of endometrial cancer and other types of solid tumors,” Marni Freeman, vice president and country medical director at GSK Canada. “This approval in Canada reaffirms our belief in the value of dostarlimab as a treatment choice for patients who are living with [recurrent or advanced] dMMR/MSI-H endometrial cancer.”

In November 2023, dostarlimab was approved in Canada for use in combination with carboplatin and paclitaxel for adult patients with primary advanced/recurrent dMMR/MSI-H endometrial cancer who are eligible for systemic therapy. Additionally, dostarlimab plus carboplatin and paclitaxel, recently received positive funding recommendations from Canada's health technology assessment bodies; this file is currently under active negotiation with the pan-Canadian Pharmaceutical Alliance.

GARNET is an ongoing multicenter, open-label, single-arm study evaluating dostarlimab monotherapy in advanced solid tumors. The study consists of 2 parts, with the second part further divided into 2 subparts (2A and 2B). Part 2B of the study includes 5 expansion cohorts: dMMR/MSI-H endometrial cancer (Cohort A1), MMR proficient (pMMR)/microsatellite stable (MSS) endometrial cancer (Cohort A2), non–small cell lung cancer (Cohort E), dMMR/MSI-H non-endometrial or POLE-mutated solid tumors (Cohort F), and platinum-resistant ovarian cancer without BRCA mutations (Cohort G).

Participants must be at least 18 years old, have a proven recurrent or advanced solid tumor, and have experienced disease progression following available anti-cancer therapies.² In Part 1 and Part 2A, patients are allowed to have any histologically or cytologically confirmed recurrent advanced solid tumor. Part 2B requires patients to have a histologically or cytologically confirmed recurrent or advanced solid tumor with measurable lesions per RECIST 1.1 criteria and must meet specific disease criteria. In cohorts A1 and A2, participants must have progressed on or after platinum doublet therapy and have received no more than 2 lines of anticancer therapy for recurrent or advanced disease.

All endometrial cancer histologies are allowed except endometrial sarcoma. MMR/MSI status must be confirmed via central immunohistochemistry lab testing before the first dose of dostarlimab. Cohort F includes participants with recurrent or advanced dMMR/MSI-H solid tumors, except endometrial and gastrointestinal cancers, who have no alternative treatment options. All participants must have adequate organ function and meet specific tissue submission requirements.

Exclusion criteria include prior therapy with anti–PD-1, anti–PD-L1, or anti–PD-L2 agents; uncontrolled central nervous system metastases; serious uncontrolled medical disorders; immunodeficiency; unresolved adverse effects from previous treatments; and participation in another investigational study within 4 weeks prior to the first dose of study drug. Participants must not have received prior anticancer therapy within 21 days or less than 5 times the half-life of the most recent therapy before day 1 of the study.

Phase 1 data from GARNET also supported the FDA approval of dostarlimab in February 2023, for patients with recurrent or advanced dMMR endometrial cancer that has progressed on prior platinum-containing therapy.³ Since then, the FDA has granted priority review to a supplemental biologics license application aiming to expand the drugs indication with chemotherapy for all patients with primary advanced or recurrent endometrial cancer, including patients with pMMR/MSS disease.⁴

References

1. Health Canada grants full approval to Jemperli for the treatment of patients with recurrent or advanced dMMR/MSI-H endometrial cancer. News release. GSK. July 25, 2024. Accessed July 25, 2024. https://www.biospace.com/health-canada-grants-full-approval-to-jemperli-for-the-treatment-of-patients-with-recurrent-or-advanced-dmmr-msi-h-endometrial-cancer
2. Study of TSR-042, an anti-programmed cell death-1 receptor (PD-1) monoclonal antibody, in participants with advanced solid tumors (GARNET). ClinicalTrials.gov. Updated August 8, 2023. Accessed July 25, 2024. https://clinicaltrials.gov/study/NCT02715284
3. FDA grants regular approval to dostarlimab-gxly for dMMR endometrial cancer. News release. FDA. February 9, 2023. Accessed July 25, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/
4. US FDA accepts for priority review GSK’s application for an expanded indication of Jemperli (dostarlimab) plus chemotherapy to include all adult patients with primary advanced or recurrent endometrial cancer. News release. GSK. April 24, 2024. Accessed July 25, 2024. https://www.gsk.com/en-gb/media/press-releases/fda-accepts-gsk-application-expanded-indication-of-jemperli-dostarlimab-plus-chemotherapy-include-all-adult-patients-primary-advanced-recurrent-endometrial-cancer/