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. 2023 Nov 14;29(22):4564-4574.
doi: 10.1158/1078-0432.CCR-22-3915.

Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study

Ana Oaknin  1 , Bhavana Pothuri  2 , Lucy Gilbert  3 , Renaud Sabatier  4 , Jubilee Brown  5 , Sharad Ghamande  6 , Cara Mathews  7 , David M O'Malley  8 , Rebecca Kristeleit  9 , Valentina Boni  10 , Adriano Gravina  11 , Susana Banerjee  12 , Rowan Miller  13 , Joanna Pikiel  14 , Mansoor R Mirza  15 , Ninad Dewal  16 , Grace Antony  17 , Yuping Dong  16 , Eleftherios Zografos  18 , Jennifer Veneris  16 , Anna V Tinker  19
Affiliations

Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study

Ana Oaknin et al. Clin Cancer Res. .

Abstract

Purpose: This interim report of the GARNET phase I trial presents efficacy and safety of dostarlimab in patients with advanced or recurrent endometrial cancer (EC), with an analysis of tumor biomarkers as prognostic indicators.

Patients and methods: A total of 153 patients with mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) and 161 patients with mismatch repair proficient (MMRp)/microsatellite stable (MSS) EC were enrolled and dosed. Patients received 500 mg dostarlimab every 3 weeks for four cycles, then 1,000 mg every 6 weeks until progression. Primary endpoints were objective response rate (ORR) and duration of response (DOR).

Results: A total of 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS EC were evaluated for efficacy. ORR was 45.5% (n = 65) and 15.4% (n = 24) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. Median DOR for dMMR/MSI-H EC was not met (median follow-up, 27.6 months); median DOR for MMRp/MSS EC was 19.4 months. The ORRs by combined positive score (CPS) ≥1 status were 54.9% and 21.7% for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORRs by high tumor mutational burden (≥10 mutations/Mb) were 47.8% (43/90) and 45.5% (5/11) for dMMR/MSI-H EC and MMRp/MSS EC, respectively. ORR in TP53mut or POLεmut molecular subgroups was 18.1% (17/94) and 40.0% (2/5), respectively. The safety profile of dostarlimab was consistent with previous reports.

Conclusions: Dostarlimab demonstrated durable antitumor activity and safety in patients with dMMR/MSI-H EC. Biomarkers associated with EC may identify patients likely to respond to dostarlimab. See related commentary by Jangra and Dhani, p. 4521.

Trial registration: ClinicalTrials.gov NCT02715284.

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Figures

Figure 1. Duration of response by cohort. Duration of response in patients with advanced or recurrent EC treated with dostarlimab monotherapy. Patients with (A) dMMR/MSI-H EC (Cohort A1) and (B) MMRp/MSS EC (Cohort A2). NR, not reached.
Figure 1.
Duration of response by cohort. Duration of response in patients with advanced or recurrent EC treated with dostarlimab monotherapy. Patients with (A) dMMR/MSI-H EC (Cohort A1) and (B) MMRp/MSS EC (Cohort A2). NR, not reached.
Figure 2. Duration of response among responders with advanced or recurrent EC treated with dostarlimab monotherapy. Patients with (A) dMMR/MSI-H EC (Cohort A1) and (B) MMRp/MSS EC (Cohort A2). Time since initial response and first and subsequent responses are shown.
Figure 2.
Duration of response among responders with advanced or recurrent EC treated with dostarlimab monotherapy. Patients with (A) dMMR/MSI-H EC (Cohort A1) and (B) MMRp/MSS EC (Cohort A2). Time since initial response and first and subsequent responses are shown.
Figure 3. Biomarker distribution in patients with advanced or recurrent EC treated with dostarlimab monotherapy. A, Percentage of EC tumors with molecular biomarkers in merged cohorts, including POLεmut, TP53mut, NSMP, or dMMR/MSI-H. B, TMB status of tumors in patients with dMMR/MSI-H EC (top) or patients with MMRp/MSS EC (bottom). C, CPS of tumors in patients with dMMR/MSI-H EC (top) or patients with MMRp/MSS EC (bottom). D, Venn diagrams showing percentages of tumors with TMB-H or CPS ≥1 or both in patients with dMMR/MSI-H EC (top) or patients with MMRp/MSS EC (bottom). aTMB status was available for 104 patients with dMMR/MSI-H tumors and 152 patients with MMRp/MSS tumors. bCPS status was available for 114 patients with dMMR/MSI-H tumors and 104 patients with MMRp/MSS tumors. TMB-NA, tumor mutational burden results were not available or undetermined.
Figure 3.
Biomarker distribution in patients with advanced or recurrent EC treated with dostarlimab monotherapy. A, Percentage of EC tumors with molecular biomarkers in merged cohorts, including POLεmut, TP53mut, NSMP, or dMMR/MSI-H. B, TMB status of tumors in patients with dMMR/MSI-H EC (top) or patients with MMRp/MSS EC (bottom). C, CPS of tumors in patients with dMMR/MSI-H EC (top) or patients with MMRp/MSS EC (bottom). D, Venn diagrams showing percentages of tumors with TMB-H or CPS ≥1 or both in patients with dMMR/MSI-H EC (top) or patients with MMRp/MSS EC (bottom). aTMB status was available for 104 patients with dMMR/MSI-H tumors and 152 patients with MMRp/MSS tumors. bCPS status was available for 114 patients with dMMR/MSI-H tumors and 104 patients with MMRp/MSS tumors. TMB-NA, tumor mutational burden results were not available or undetermined.
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