PHILADELPHIA—GlaxoSmithKline plc (GSK) has reported new data from an updated analysis of the GARNET trial, which demonstrated that dostarlimab provided clinically meaningful results in women with recurrent or advanced mismatch repair-deficient (dMMR) endometrial cancer who progressed either on or after a platinum-based regimen.
Dostarlimab is an investigational humanized anti-PD-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and blocks its interaction with the ligands PD-L1 and PD-L2. The therapy is also being investigated for women with recurrent or primary advanced endometrial cancer in combination with standard of care (chemotherapy) in the Phase 3 RUBY trial. Dostarlimab is also being evaluated in combination with other therapeutic agents for patients with advanced solid tumors or metastatic cancer.
“We are committed to developing medicines for patients who face high unmet medical need,” said Dr. Axel Hoos, senior vice president and head oncology R&D, GSK. “We believe in the clinical potential of dostarlimab for women with advanced or recurrent dMMR endometrial cancer who urgently need additional treatment options for this incurable disease.”
The updated GARNET analysis included patients with dMMR endometrial cancer who had measurable disease at baseline and ≥6 months of follow-up by the data cutoff (n=71). Patients received 500 mg of dostarlimab once every three weeks for four doses, followed by 1,000 mg once every six weeks until disease progression. The primary endpoints were confirmed objective response rate (ORR) and duration of response (DOR), as assessed against RECIST v 1.1 by blinded independent central review. GARNET is the largest dataset evaluating an anti-PD-1 in endometrial cancer.
Treatment with dostarlimab showed an ORR of 42% and a disease control rate of 58%. Overall, 13% of patients had a complete response and 30% of patients had a partial response. At the time of data cutoff, with a median follow up of 11.2 months, the median DOR had not been reached.
“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,” added Dr. Ana Oaknin, head of the Gynecologic Cancer Program at Vall d’Hebron Institute of Oncology, Barcelona, and primary investigator for GARNET.
The safety population included all patients with dMMR endometrial cancer who received at least one dose of dostarlimab (n=104). Results showed that dostarlimab was well tolerated, with a low discontinuation rate (2%) due to treatment-related adverse events (TRAEs), consistent with the safety profiles of other anti-PD-1 therapies. The most commonly reported TRAEs were asthenia (15%), diarrhea (15%), fatigue (14%) and nausea (13%). No deaths associated with dostarlimab were reported in the study.
The ongoing Phase 1 GARNET trial is evaluating dostarlimab as monotherapy in patients with advanced solid tumors. Part 2B of the study includes five expansion cohorts: dMMR/microsatellite instability-high (MSI-H) endometrial cancer (cohort A1), mismatch repair-proficient endometrial cancer (cohort A2), non-small cell lung cancer (cohort E), dMMR/MSI-H non-endometrial cancer (cohort F) and platinum-resistant ovarian cancer without BRCA mutations (cohort G). GARNET is still enrolling patients.