TY - JOUR
T1 - Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer
T2 - Interim Results of the Phase I GARNET Study
AU - Oaknin, Ana
AU - Pothuri, Bhavana
AU - Gilbert, Lucy
AU - Sabatier, Renaud
AU - Brown, Jubilee
AU - Ghamande, Sharad
AU - Mathews, Cara
AU - O'Malley, David M
AU - Kristeleit, Rebecca
AU - Boni, Valentina
AU - Gravina, Adriano
AU - Banerjee, Susana
AU - Miller, Rowan
AU - Pikiel, Joanna
AU - Mirza, Mansoor R
AU - Dewal, Ninad
AU - Antony, Grace
AU - Dong, Yuping
AU - Zografos, Eleftherios
AU - Veneris, Jennifer
AU - Tinker, Anna V
PY - 2023/11/14
Y1 - 2023/11/14
N2 - 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.
AB - 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.
KW - Antibodies, Monoclonal, Humanized
KW - Biomarkers, Tumor/genetics
KW - Colorectal Neoplasms/pathology
KW - DNA Mismatch Repair
KW - Endometrial Neoplasms/drug therapy
KW - Female
KW - Humans
KW - Microsatellite Instability
KW - Neoplasm Recurrence, Local/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85174301764&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-22-3915
DO - 10.1158/1078-0432.CCR-22-3915
M3 - Journal article
C2 - 37363992
SN - 1078-0432
VL - 29
SP - 4564
EP - 4574
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 22
ER -