Dostarlimab on the Road to Progress in dMMR Endometrial Cancer

Dostarlimab (TSR-042), an investigational humanized anti–PD-1 monoclonal antibody, led to clinically meaningful responses in female patients with recurrent or advanced mismatch repair–deficient (dMMR) endometrial cancer who progressed on or after a platinum-based regimen, according to an updated analysis of the phase I GARNET trial (NCT02715284).¹

“There are limited treatment options for women with advanced or recurrent endometrial cancer, and prognosis of these patients is poor. The results observed in the GARNET trial indicate the potential of dostarlimab to offer a new treatment option for women with this challenging disease,” said Ana Oaknin, MD, head of the Gynaecologic Cancer Program at Vall d’Hebron Institute of Oncology, Barcelona, and primary investigator for GARNET, in a statement.

Results were presented in a webinar for the virtual 2020 Society of Gynecologic Oncology (SGO) Annual Meeting.²

The interim analysis included 70 patients with dMMR endometrial cancer who had been followed for ≥6 months at the time of data cutoff. All patients had measurable disease at baseline and were a median of 64.5 years of age.³

The overall response rate (ORR) observed with dostarlimab treatment was 42% (95% CI, 31%-55%), which included confirmed complete responses (CRs) in 13% of patients (n = 9) and confirmed partial responses (PRs) in 30% of patients (n = 21). Stable disease was seen in 16% of the study population (n = 11), and about one third of patients had progressive disease. The disease control rate was 58% (95% CI, 45%-69%). At a median follow-up of 11.2 months at the time of data cutoff, the median duration of response (DOR) was not yet reached (range, 1.87+ to 19.61+ months).

For the safety analysis, all patients with dMMR endometrial cancer who received at least one dose of dostarlimab were included (n = 104). One or more treatment-related adverse events (TRAEs) were observed in 71% of patients (n = 50). The most common TRAEs overall were asthenia (15%), diarrhea (15%), fatigue (14%), and nausea (13%), which each occurred in 16% of patients.¹ Grade ≥3 TRAEs were observed in 14% of study participants (n = 10), with the most common being lipase increase; transaminases increase; and colitis, diarrhea, and anemia, each occurring in 3% of patients. Treatment discontinuation was seen in 2% of patients (n = 2), which was a result of TRAEs. Twenty-seven percent of patients (n = 19) experienced any-grade immune-related TRAEs and 10% experienced grade ≥3 immune-related TRAEs. The most common immune-related TRAE of any grade was diarrhea, which occurred in 6% of patients. Overall, 6% of patients succumbed to an adverse event (n = 4); however, no deaths were related to dostarlimab.²

Oaknin et al concluded from these preliminary data that dostarlimab has clinical activity in patients with previously treated recurrent or advanced dMMR endometrial cancer and has an acceptable safety profile.

In the GARNET study, dostarlimab was administered at 500 mg, every 3 weeks for the first 4 cycles. Then, the agent was given at 1000 every 6 weeks until disease progression or discontinuation. The coprimary end points evaluated in the study were ORR and DOR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by blinded independent central review. The key secondary end point included DCR and safety.

During the SGO webinar, Melissa A. Geller, MD, MS, of the University of Minnesota explained the implication of these data: “Dostarlimab gives us another option for checkpoint inhibition in mismatch repair deficient tumors following chemotherapy.”

Following the SGO presentation, during a question and answer session, a coinvestigator of the GARNET study, Jubilee Brown, MD, of Levine Cancer Institute, Carolinas HealthCare System stated that although data from the microsatellite stable population were not presented at the meeting, another data cutoff is upcoming and results are expected later in 2020.

_References

_{1. GSK presents new data from the GARNET study demonstrating potential of dostarlimab to treat a subset of women with recurrent or advanced endometrial cancer [news release]. London, United Kingdom: GSK; April 24, 2020. https://bit.ly/3cHCWzR. Accessed April 24, 2020.}

_{2. Geller, MA. The road to progress in endometrial cancer. Society of Gynecologic Oncology Annual Meeting webinar [published on April 23, 2020]. https://bit.ly/2Kwn33c. Accessed April 24, 2020.}

_{3. Oaknin, A, Tinker AV, Gilbert L, et al. Safety and efficacy of the anti–PD-1 monoclonal antibody dostarlimab in patients with recurrent or advanced dMMR endometrial cancer. Presented at: Society of Gynecologic Oncology Annual Meeting: March 28, 2020. Abstract 9}.