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oai:recercat.cat:11351/106632024-06-06T08:39:51Zcom_2072_378070com_2072_378040col_2072_378092

Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study Pothuri, Bhavana Gilbert, Lucy Brown, Jubilee Ghamande, Sharad OAKNIN, ANA Sabatier, Renaud Institut Català de la Salut [Oaknin A] Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pothuri B] Gynecologic Oncology Group (GOG) and Department of Obstetrics/Gynecology, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, USA. [Gilbert L] Division of Gynecologic Oncology, McGill University Health Centre, Montreal, Quebec, Canada. [Sabatier R] Department of Medical Oncology, Institut Paoli Calmettes, Aix-Marseille University, Marseille, France. [Brown J] Division of Gynecologic Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, USA. [Ghamande S] Department of Obstetrics and Gynecology, Georgia Cancer Center, Augusta University, Augusta, Georgia Vall d'Hebron Barcelona Hospital Campus Anticossos monoclonals - Ús terapèutic Avaluació de resultats (Assistència sanitària) Endometri - Càncer - Tractament DISEASES::Neoplasms::Neoplasms by Site::Urogenital Neoplasms::Genital Neoplasms, Female::Uterine Neoplasms::Endometrial Neoplasms CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Monoclonal::Antibodies, Monoclonal, Humanized ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias urogenitales::neoplasias de los genitales femeninos::neoplasias uterinas::neoplasias endometriales COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos monoclonales::anticuerpos monoclonales humanizados TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento Eficàcia; Biomarcador; Càncer d'endometri Eficacia; Biomarcador; Cáncer de endometrio Efficacy; Biomarker; Endometrial cancer 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. The GARNET trial (NCT02715284) was originally designed and funded by Tesaro Inc. (acquired by GSK in 2018) in collaboration with the authors 2023-11-28T07:19:42Z 2023-11-28T07:19:42Z 2023-11-15 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Oaknin A, Pothuri B, Gilbert L, Sabatier R, Brown J, Ghamande S, et al. Safety, Efficacy, and Biomarker Analyses of Dostarlimab in Patients with Endometrial Cancer: Interim Results of the Phase I GARNET Study. Clin Cancer Res. 2023 Nov 15;29(22):4564–74. 1557-3265 https://hdl.handle.net/11351/10663 10.1158/1078-0432.CCR-22-3915 37363992 http://hdl.handle.net/11351/10663 eng Clinical Cancer Research;29(22) https://doi.org/10.1158/1078-0432.CCR-22-3915 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf American Association for Cancer Research Scientia