Abstract
BackgroundCarboplatin-paclitaxel is standard systemic anticancer therapy for recurrent or advanced EC for which surgery and/or radiation are not curative. Dostarlimab (TSR-042) is an anti-programmed cell death (PD)-1 humanised monoclonal antibody that has demonstrated antitumour activity and an acceptable safety profile in patients (pts) with recurrent or advanced EC in the GARNET trial. The RUBY trial will evaluate the efficacy and safety of dostarlimab in combination with carboplatin-paclitaxel in recurrent or primary advanced EC compared with carboplatin-paclitaxel alone.Trial DesignThis is a global, randomised, double-blind, multicenter, placebo-controlled study. Eligible pts must have first recurrent or primary stage III or stage IV EC with a low potential for cure by radiation therapy or surgery alone or in combination. Pts with carcinosarcoma are eligible for enrolment. 470 pts will be enrolled from approximately 160 sites in the ENGOT countries, United States, and Canada. Stratification factors are DNA mismatch repair status (proficient [p], or deficient [d] MMR), prior external pelvic radiotherapy (yes or no), and disease status (recurrent, primary stage III or primary stage IV). Pts will be randomised 1:1 to receive combination dostarlimab 500 mg or placebo + carboplatin AUC 5 + paclitaxel 175 mg/m2 every 3 weeks for 6 cycles followed by dostarlimab 1000 mg or placebo monotherapy every 6 weeks for up to 3 years in the absence of progressive disease, death, unacceptable toxicity, or patient/physician decision to withdraw from the study. The primary endpoint is progression-free survival (PFS) as assessed by the investigator in the all-comers population and the dMMR population per RECIST version 1.1. Secondary efficacy endpoints are PFS assessed by blinded independent central review per RECIST version 1.1, overall survival, objective response rate, duration of response, disease control rate, safety and tolerability, and patient-reported outcomes.DisclosuresSponsor: GlaxoSmithKline, Waltham, MA, USANCT number: NCT03981796Encore statement: This data is presented on behalf of the original authors with their permission. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, May 29–31, 2020, Virtual.Dr. Mirza reports personal fees and other from Karyopharm Therapeutics; Personal fees and other from Sera Prognostics and Roche; Grants and Personal fees from AstraZeneca, Clovis Oncology, Pfizer, GSK, Genmab, BioCad, Sotio, Boehringer Ingelheim, Geneos Therapeutics, Merck, Oncology Venture, Seattle Genetics, Sera Prognostics,Takeda Pharmaceutical Company Ltd, and Zailab.Dr. Coleman reports consulting fees from Merck, Reoche/Genentech, AstraZeneca, Oncomed/Mateo, Novocure, Oncosec, Janssen, Clovis, Tesaro/GSK, Abbvie, Eisai, Arrivive, and Oncoquest; grants from Merck, Roche/Genentech, V-Foundation, AstraZeneca, Janssen, Clovis, Genmab and Abbvie; and honoraria/reimbursement from Merck, Roche/Genentech, AstraZeneca, Oncomed/Mateo, Novocure, Oncosec, Janssen, Clovis, Tesaro/GSK, Eisai, Arrivive and OncoQuest.Dr. Slomovitz reports consulting/advisory fees from GlaxoSmithKline.Dr. Powell reports consulting/advisory fees from Roche/Genentech, AstraZeneca, Tesaro, and Clovis Oncology; and speakers’ bureau at Genentech/Roche, AstraZeneca, Tesaro and Clovis Oncology.Drs. Hanker and Valabrega have nothing to disclose.Drs. Im, Walker, and Guo are employees of GlaxoSmithKline.
