FDA Approves Dostarlimab-gxly for dMMR Recurrent or Advanced Solid Tumors

FDA

The FDA has granted an accelerated approval to dostarlimab-gxly (Jemperli) for the treatment of adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, who have progressed on or following previous treatment and who have no satisfactory alternative options.¹

The regulatory decision is supported by collective data from the dMMR endometrial cancer cohort A1 and the dMMR solid-tumor, non-endometrial cancer, cohort F of the ongoing phase 1 GARNET trial (NCT02715284).

Findings indicated that the agent elicited an objective response rate (ORR) of 41.6% (95% CI, 34.9-48.6) in all dMMR solid tumors, including endometrial and non-endometrial solid tumors (n = 209); this included a partial response (PR) rate of 32.5%. Moreover, the median duration of response (DOR) was 34.7 months (range 2.6-35.8+) with 95.4% of patients experiencing a response that persisted for 6 months or longer. In the dMMR solid tumor non-endometrial cancer cohort (n = 106), the ORR with dostarlimab was 38.7% (95% CI, 29.4-48.6).

“For patients with tumors expressing the dMMR biomarker, there continues to be a significant need for new and effective treatments. I’m excited about GlaxoSmithKline [GSK]'s second oncology FDA approval this year, and the new treatment option it provides for these patients," Hal Barron, MD, chief scientific officer and president of R&D at GSK, stated in a press release.

GARNET trial is an ongoing, multicenter, non-randomized, multiple parallel-cohort, open-label study that is examining dostarlimab as a single agent in patients with advanced solid tumors. Part 2B of the study comprises 5 expansion cohorts: dMMR/MSI-H endometrial cancer (cohort A1), mismatch repair proficient/microsatellite stable endometrial cancer (cohort A2), non–small cell lung cancer (cohort E), dMMR/MSI-H non-endometrial or POLE-mutated solid tumor basket cohort (cohort F), and platinum-resistant ovarian cancer without BRCA mutations (cohort G).

To be eligible for enrollment, patients enrolled to cohort A1 needed to have progressed on or after previous treatment with a platinum-containing regimen. Patients enrolled to cohort F were required to have progressed following systemic therapy and could not have any satisfactory alternative treatment options available to them. Moreover, patients with colorectal cancer must have had progressive disease after, or have been intolerant to, fluoropyrimidine, oxaliplatin, and irinotecan.

Study participants were given dostarlimab via intravenous infusion at a dose of 500 mg once every 3 weeks for 4 total doses; this was followed by a dose of 1000 mg once every 6 weeks. Treatment was given until either progressive disease or intolerable toxicity.

A total of 267 patients with recurrent or advanced dMMR solid tumors were determined to be evaluable for safety. The most frequently experienced adverse effects (AEs), which occurred in 20% or more of patients, included fatigue/asthenia (42%), anaemia (30%), diarrhea (25%) and nausea (22%).

The most commonly experienced grade 3 or 4 AEs, which were reported in 2% or more of patients, were anemia, fatigue/asthenia, increased transaminases, sepsis, and acute kidney injury. Grade 3 or 4 laboratory abnormalities, which were reported in 2% or more of patients, comprised decreased lymphocytes, decreased sodium, increased alkaline phosphatase. and decreased albumin.

Previously, in April 2021, the FDA granted an accelerated approval to dostarlimab for use in adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, who have progressed on or after previous treatment with a platinum-containing regimen.²

The decision was based on findings from cohort A1 of GARNET, which included a total of 71 patients with dMMR endometrial cancer. At the time, dostarlimab had elicited a 42.3% ORR, which included a 12.7% complete response rate and a 29.6% PR rate.

With the new approval, the US prescribing information for the indication comprises efficacy information for 32 additional patients in the endometrial cancer cohort A1 (n = 103). Additional data from this cohort revealed an ORR of 44.7% (95% CI, 34.9%-54.8%) with dostarlimab. The DOR with the agent was reported to range from 2.6 months to 35.8+ months.

Notably, the data from the endometrial cancer cohort of the GARNET trial represent the largest dataset to date examining an anti–PD-1 inhibitor as single-agent treatment for patients with endometrial cancer, according to GSK.

“Dostarlimab is an important new treatment option for patients with mismatch repair-deficient recurrent or advanced solid cancers who have progressed and have no alternative options," GARNET study investigator, as well as professor and division director of Gynecologic Oncology at Atrium Health Levine Cancer Institute, stated in a press release. "As we saw in the GARNET trial, of those patients who respond to treatment with dostarlimab, nearly all continued to respond for six months or longer.”

References

1. GSK receives FDA accelerated approval for JEMPERLI (dostarlimab-gxly) for adult patients with mismatch repair-deficient (dMMR) recurrent or advanced solid tumors. News release. GlaxoSmithKline. August 17, 2021. Accessed August 17, 2021. https://bit.ly/3yVSiMN
2. FDA approves immunotherapy for endometrial cancer with specific biomarker. News release. FDA. April 22, 2020. Accessed August 17, 2021. https://prn.to/3ngdVSL