Abstract 820TiP
Background
Carboplatin-paclitaxel is standard of care for recurrent/advanced EC for which surgery ± radiation are not curative. Dostarlimab is an anti–programmed cell death 1 (PD-1) humanized monoclonal antibody that showed antitumor activity and an acceptable safety profile in patients (pts) with recurrent or advanced EC in the GARNET trial. Niraparib is a PARP inhibitor (PARPi) approved as 1L maintenance therapy in pts with advanced ovarian cancer following response to platinum-based chemo. Based on mechanism of action and preclinical findings, PARPi are being investigated for use in EC. RUBY part 2 will evaluate the efficacy and safety of dostarlimab + carboplatin-paclitaxel followed by dostarlimab + niraparib in recurrent/advanced EC.
Trial design
RUBY is a 2-part global, randomized, double-blind, PBO-controlled study. Eligible pts must have recurrent or advanced stage III or IV EC with a low potential for cure by radiation ± surgery. Pts with carcinosarcoma are eligible. For part 2, ≈270 pts will be enrolled from ≈20 ENGOT- and GOG-affiliated countries and Canada. Stratification factors are DNA mismatch repair/microsatellite instability (MMR/MSI) status (dMMR/MSI-H or MMRp/MSS), prior external pelvic radiotherapy (yes/no), and disease status (recurrent, primary stage III, primary stage IV). Pts will be randomized 2:1 to receive dostarlimab 500 mg or PBO + carboplatin AUC 5 mg/mL/min + paclitaxel 175 mg/m2 IV Q3W for 6 cycles followed by dostarlimab 1000 mg IV Q6W + niraparib 200 mg or 300 mg PO QD or PBO (IV and PO) for up to 3 y until progressive disease, death, unacceptable toxicity, or withdrawal. Niraparib dosing is 200 mg PO QD for pts with baseline body weight (BW) <77 kg or platelet count (PC) <150,000/μL or 300 mg QD for pts with baseline BW ≥77 kg and PC ≥150,000/μL. The primary endpoint is PFS assessed by blinded independent central review in the intention-to-treat population per RECIST v1.1. Secondary endpoints are PFS based on investigator assessment per RECIST v1.1, OS, ORR, DOR, DCR, safety and tolerability, and pt-reported outcomes.
Clinical trial identification
NCT03981796.
Editorial acknowledgement
Writing and editorial support, funded by GlaxoSmithKline (Waltham, MA, USA) and coordinated by Heather Ostendorff-Bach, PhD, of GlaxoSmithKline were provided by Betsy Taylor, PhD, and Jennifer Robertson, PhD, of Ashfield MedComms, an Ashfield Health company (Middletown, CT, USA).
Legal entity responsible for the study
GlaxoSmithKline.
Funding
GlaxoSmithKline.
Disclosure
M.R. Mirza: Financial Interests, Personal, Leadership Role: Karyopharm Therapeutics and Sera Prognostics; Financial Interests, Institutional, Research Grant: 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; Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Roche, Pfizer, GSK, Genmab, BioCad, Sotio, Boehringer Ingelheim, Geneos Therapeutics, Merck, Oncology Venture, Seattle Genetics, Sera Prognostics, Takeda Pharmaceutical Company Ltd, and Zailab. R.L. Coleman: Financial Interests, Personal, Advisory Role: Merck, Roche/Genentech, AstraZeneca, OncoMed/Mateo, Novocure, Oncosec, Janssen, Clovis, Tesaro/GSK, AbbVie, Eisai, Arrivive, and Oncoquest; Financial Interests, Institutional, Research Grant: Merck, Roche/Genentech, V-Foundation, AstraZeneca, Janssen, Clovis, Genmab, and AbbVie; Financial Interests, Personal, Advisory Role, honoraria: Merck, Roche/Genentech, AstraZeneca, OncoMed/Mateo, Novocure, Oncosec, Janssen, Clovis, Tesaro/GSK, Eisai, Arrivive, and OncoQuest. L. Hanker: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, Roche, and Tesaro. B. Slomovitz: Financial Interests, Personal, Advisory Role: GlaxoSmithKline. G. Valabrega: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Clovis Oncology, GlaxoSmithKline, PharmaMar, Roche, and Tesaro. L. DeMars: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. M. Walker: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. T. Duan: Financial Interests, Personal, Full or part-time Employment: GlaxoSmithKline. M. Powell: Financial Interests, Personal, Advisory Role: Roche/Genentech, AstraZeneca, Tesaro, and Clovis Oncology.