37MO - Dostarlimab plus chemotherapy in primary advanced or recurrent endometrial cancer (pA/rEC) in the RUBY trial: Overall survival (OS) by MMR status and molecular subgroups

Background

At interim analysis (IA) 1 of Part 1 of the RUBY trial (NCT03981796), statistically significant benefit in PFS was observed with dostarlimab+carboplatin-paclitaxel (D+CP) vs placebo (PBO)+CP in the overall and mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) populations of pts with pA/rEC. Here we report OS from IA2.

Methods

Pts with pA/rEC were randomized 1:1 to D+CP or PBO+CP followed by D or PBO for ≤3 years or until progression. OS was a dual-primary endpoint in the overall population and a prespecified, exploratory analysis in the dMMR/MSI-H and mismatch repair proficient/microsatellite stable (MMRp/MSS) populations. OS by molecular subgroup was a post-hoc analysis. Safety was a secondary endpoint.

Results

494 pts were randomized (245 D+CP; 249 PBO+CP). In the overall population, there was a significant reduction in the risk of death by 31% and clinically meaningful improvement of 16.4 mo in median OS (mOS) for D+CP vs PBO+CP (Table). In the dMMR/MSI-H population, hazard ratio (HR) for OS was 0.32; mOS was not reached for D+CP and was 31.4 mo for PBO+CP. In the MMRp/MSS population, HR for OS was 0.79; mOS was 34.0 mo for D+CP and 27.0 mo for PBO+CP. At IA2, in 400 pts with whole exome sequencing, a trend towards clinical benefit with D+CP was observed in the dMMR/MSI-H, TP53 mutated, and no specific molecular profile subgroups.

Table: 37MO

Safety at IA2 was similar to IA1

^aAnalyses were conducted in 400 patients with whole exome sequencing results. Mut, mutant; NR, not reached; NSMP, no specific molecular profile.

Conclusions

D+CP showed statistically significant and clinically relevant OS benefit in the overall population compared with CP alone. A substantial survival difference was seen in the dMMR/MSI-H population. In the MMRp/MSS population, there was a 7 mo difference in median OS vs CP alone, with a 21% risk reduction for death. OS by molecular subgroup at IA2 was consistent with IA1. RUBY is the only trial to demonstrate a statistically significant OS benefit in pts with pA/rEC and supports the use of dostarlimab+CP as a standard of care in the 1L setting.

Clinical trial identification

NCT03981796.

Editorial acknowledgment

Writing and editorial support, funded and coordinated by GSK (Waltham, MA, USA), was provided by Shannon Morgan-Pelosi, PhD, CMPP, and Kathleen Blake, PhD, of Ashfield MedComms, an Inizio company. Portions of this data were previously presented at the Society of Gynecologic Oncology (SGO) 2024 Congress; March 16–18, 2024; San Diego, California and are presented on behalf of the original authors with their permission. Reused with permission.

Legal entity responsible for the study

GSK.

Funding

GSK.

Disclosure

M.A. Powell: Financial Interests, Personal, Research Grant: GSK; Financial Interests, Personal, Other, honoraria/consultation fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Immunogen, Merck. A. Auranen: Financial Interests, Personal, Advisory Board: GSK, MSD. L.J. Willmott: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eisai, Immunogen, Merck, Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca, Immunogen, Seagen. L. Gilbert: Financial Interests, Institutional, Other, Grants: Alkermes, AstraZeneca, Clovis, Esperas, ImmunoGen Inc, IMV, Karyopharm, Merck Sharp & Dohme, Mersana, Novocure GmbH, OncoQuest Pharmaceuticals, Pfizer, Roche, Tesaro; Financial Interests, Personal, Other, consulting fees: Merck; Financial Interests, Personal, Other, honoraria: Alkermes, AstraZeneca, Eisai, Eisai-Merck, GSK. D. Black: Financial Interests, Institutional, Other, grants: GSK; Financial Interests, Personal, Other, member: GOG Partners Investigational Council; Financial Interests, Personal, Other, medical director/owner: Trials365, LLC. D. Cibula: Financial Interests, Personal, Advisory Board: Akesobio, AstraZeneca, GSK, MSD, Novocure, Roche, Seagen, Sotio. G. Valabrega: Financial Interests, Personal, Other, consulting/advisory fees: Amgen, AstraZeneca, Clovis Oncology, GSK, PharmaMar, Roche, Tesaro. L.C. Hanker: Financial Interests, Personal, Other, consulting/advisory fees: Amgen, AstraZeneca, Clovis, Eisai, GSK, Intuitive Surgery, Janssen, MSD, Novartis, Pfizer, Pharma Mar, Roche, Tesaro. A. Stuckey: Financial Interests, Personal, Other, royalties: UptoDate reviewer. I.A. Boere: Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Advisory Board: AstraZeneca, GSK. M.S. Shahin: Financial Interests, Institutional, Other, grants: AstraZeneca, GSK, Merck; Financial Interests, Personal, Other, honoraria: AstraZeneca, GSK, Merck, Seagen; Financial Interests, Personal, Expert Testimony: Robindon & Havens PSC, Lexington KY; Financial Interests, Personal, Advisory Board: Seagen; Financial Interests, Personal, Other, board member: Unite for Her. B. Pothuri: Financial Interests, Institutional, Other, grant support: AstraZeneca, Celsion, Clovis Oncology, Eisai, Genentech/Roche, Karyopharm, Merck, Mersana, SeaGen, Sutro Biopharma, Takeda Pharmaceuticals, Tesaro/GSK, Toray, VBL Therapeutics; Financial Interests, Personal, Other, consulting fees: AstraZeneca, Atossa, Clovis Oncology, Deciphera, Elevar Therapeutics, Imab, Merck, Mersana, Sutro Biopharma, Tesaro/GSK, Toray; Other, Personal, Other, support for attending meetings: GOG Foundation; Financial Interests, Personal, Advisory Board: Arquer Diagnostics, AstraZeneca, Atossa, Clovis Oncology, Deciphera, Eisai, Elevar Therapeutics, GOGFoundation, Imab, Eli Lilly, Merck, Mersana, Seagen, Sutro Biopharma, Tesaro/GSK, Toray, VBL Therapeutics; Non-Financial Interests, Personal, Invited Speaker, leadership: NYOB Society Secretary, SGO Clinical Practice Committee Chair, SGO COVID-19 Taskforce Co-Chair. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Clovis, Genentech, GSK, GOG Foundation, Merck, Myriad, Jazz Pharma, Onconova, Nuvation Bio, EQRX, Regeneron, Eisai, Incyte; Financial Interests, Personal, Member of Board of Directors: GOG Foundation, HOW: Hearing Ovarian Cancer Whispers. M. Grimshaw, S. Stevens: Financial Interests, Personal, Full or part-time Employment: GSK. R.L. Coleman: Financial Interests, Personal, Other, grants or contracts: AstraZeneca, Clovis, Genelux, Genmab, Merck, Immunogen, Roche/Genentech; Financial Interests, Personal, Other, consulting fees: AbbVie, Agenus, Alkermes, AstraZeneca, Clovis, Deciphera, Genelux, Genmab, GSK, Immunogen, Novocure, Merck, OncoQuest, Onxerna, Regeneron, Roche/Genentech; Financial Interests, Personal, Other, participation on a data safety monitoring board or advisory board: Eisai/BMS, VBL Therapeutics. M.R. Mirza: Financial Interests, Institutional, Research Grant: Allarity, Apexigen, AstraZeneca, Boehringer Ingelheim, Clovis, GSK, Novartis, Ultimovacs; Financial Interests, Personal, Other, trial chair: Deciphera, Mersana, NuvationBio; Financial Interests, Personal, Invited Speaker: AstraZeneca, GenMab, GSK, Mersana, Seagen, Takeda; Financial Interests, Personal, Member of Board of Directors, and holds stocks and shares: Karyopharm, Sera Prognostics. All other authors have declared no conflicts of interest.