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Ref Type Journal Article
PMID (33001143)
Authors Oaknin A, Tinker AV, Gilbert L, Samouëlian V, Mathews C, Brown J, Barretina-Ginesta MP, Moreno V, Gravina A, Abdeddaim C, Banerjee S, Guo W, Danaee H, Im E, Sabatier R
Title Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial.
Journal Vol Issue Date Pages Journal Short Title
JAMA oncology 2020 Oct 01 1766-1772 JAMA Oncol
URL
Abstract Text Deficient mismatch mutation repair mechanisms may sensitize endometrial cancers to anti-programmed death 1 (PD-1) therapies. Dostarlimab (TSR-042) is an investigational anti-PD-1 antibody that binds with high affinity to the PD-1 receptor.To assess the antitumor activity and safety of dostarlimab for patients with deficient mismatch repair endometrial cancer.This ongoing, open-label, single-group, multicenter study began part 1 on March 7, 2016, and began enrolling patients with deficient mismatch mutation repair endometrial cancer on May 8, 2017. Median follow-up was 11.2 months (range, 0.03 [ongoing] to 22.11 [ongoing] months; based on radiological assessments). Statistical analysis was performed July 8 to August 9, 2019.Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, treatment discontinuation, or withdrawal.The primary end point was objective response rate and duration of response by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1.As of the data cutoff, 104 women (median age, 64.0 years [range, 38-80 years]) with deficient mismatch mutation repair endometrial cancers were enrolled and treated with dostarlimab. Of these, 71 had measurable disease at baseline and at 6 months or more of follow-up and were included in the analysis. There was a confirmed response in 30 patients (objective response rate, 42.3%; 95% CI, 30.6%-54.6%); 9 patients (12.7%) had a confirmed complete response, and 21 patients (29.6%) had a confirmed partial response. Responses were durable; the median duration of response was not reached (median follow-up was 11.2 months). The estimated likelihood of maintaining a response was 96.4% at 6 months and 76.8% at 12 months. Anemia (3 of 104 [2.9%]), colitis (2 of 104 [1.9%]), and diarrhea (2 of 104 [1.9%]) were the most common grade 3 or higher treatment-related adverse events.In this nonrandomized trial, dostarlimab was associated with clinically meaningful and durable antitumor activity with an acceptable safety profile for patients with deficient mismatch mutation repair endometrial cancers after prior platinum-based chemotherapy.ClinicalTrials.gov identifier: NCT02715284.

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Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
MLH1 negative endometrial cancer sensitive Dostarlimab-gxly FDA approved - On Companion Diagnostic Actionable In a Phase I trial (GARNET) that supported FDA approval, Jemperli (dostarlimab-gxly) treatment demonstrated acceptable safety profile, and resulted in an objective response rate of 42.3% (30/71, 9 complete responses, 21 partial responses), with a median duration of response not reached in patients with recurrent or advanced endometrial cancer harboring mismatch repair deficiency (dMMR) as confirmed by a loss of MLH1, PMS2, MSH2, or MSH6 expression in an FDA-approved IHC test (PMID: 33001143; NCT02715284). detail... 33001143 detail...
MSH6 negative endometrial cancer sensitive Dostarlimab-gxly FDA approved - On Companion Diagnostic Actionable In a Phase I trial (GARNET) that supported FDA approval, Jemperli (dostarlimab-gxly) treatment demonstrated acceptable safety profile, and resulted in an objective response rate of 42.3% (30/71, 9 complete responses, 21 partial responses), with a median duration of response not reached in patients with recurrent or advanced endometrial cancer harboring mismatch repair deficiency (dMMR) as confirmed by a loss of MLH1, PMS2, MSH2, or MSH6 expression in an FDA-approved IHC test (PMID: 33001143; NCT02715284). detail... 33001143 detail...