38MO - Progression-free survival (PFS) in primary advanced or recurrent endometrial cancer (pA/rEC) in the overall and mismatch repair proficient (MMR/MSS) populations and in histological and molecular subgroups: Results from part 2 of the RUBY trial

Background

In Part 1 of the phase 3 RUBY trial (NCT03981796) in pA/rEC, patients (pts) receiving dostarlimab (dostar)/carboplatin-paclitaxel (CP) exhibited significant benefits in PFS and overall survival versus CP alone. Outcomes may be further improved by adding a poly(ADP-ribose) polymerase inhibitor (PARPi). Here we report results from Part 2 of RUBY of dostar/CP followed by dostar/niraparib (nira; a PARPi) maintenance therapy in pts with pA/rEC.

Methods

Pts were randomized 2:1 to dostar 500 mg IV + CP Q3W for 6 cycles followed by dostar 1000 mg IV Q6W + nira (individualized starting dose of 200 or 300 mg) PO daily for ≤3 years from randomization or to placebo (PBO) + CP Q3W for 6 cycles followed by PBOs for ≤3 years. The primary endpoint was PFS in the overall and MMRp/MSS populations.

Results

291 pts were randomized (192 dostar/CP + dostar/nira; 99 PBO/CP). PFS was significantly improved in pts receiving dostar/CP + dostar/nira vs PBO/CP in the overall and MMRp/MSS populations (Table). In pts with endometrioid carcinoma, pts with other histologies, and across most biomarker subgroups (eg, TP53mut), the hazard ratio (HR) directionally favored dostar/CP + dostar/nira in the overall and MMRp/MSS populations. The safety profile observed was consistent with those of the individual agents. Table: 38MO

PFS

^a<20 events. ^bBased on whole exome sequencing.

Conclusions

RUBY Part 2 met its primary endpoint and is the first study to show significant and clinically meaningful improvement in PFS in the MMRp/MSS and overall populations. The trial is ongoing for OS follow-up. The safety profile observed was generally consistent with the known safety profiles of the individual agents. These data demonstrate a potential role for PARPi maintenance in pts receiving dostar/CP, especially for MMRp/MSS tumors.

Clinical trial identification

NCT03981796.

Editorial acknowledgment

Writing and editorial support, funded and coordinated by GSK (Waltham, MA, USA), was provided by Charlette Tiloke, PhD, Kristoffer Myczek, PhD, and Kathleen Blake, PhD, of Ashfield MedComms, an Inizio company. Encore Statement: 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.R. Mirza: Financial Interests, Personal, Other, consulting fees: AstraZeneca, Biocad, GSK, Karyopharm, Merck, Roche, Zailab; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, GSK; Financial Interests, Institutional, Funding, research: Apexigen, AstraZeneca, Deciphera (trial chair), GSK, Ultimovacs; Financial Interests, Personal, Member of Board of Directors, stocks/shares: Karyopharm . S. Ghamande: Financial Interests, Institutional, Other, institutional fees: Georgia Cancer Center; Financial Interests, Personal, Speaker’s Bureau, consulting: Eisai, GSK. L.C. Hanker: Financial Interests, Personal, Other, consulting/advisory fees: Amgen, AstraZeneca, Clovis, Eisai, GSK, Intuitive Surgery, Janssen, MSD, Novartis, Pfizer, PharmaMar, Roche, Tesaro. D. Black: Financial Interests, Institutional, Other, grant fees: GSK; Financial Interests, Personal, Member: GOG Partners Investigational Council; Financial Interests, Personal, Other, medical director/owner: Trials365, LLC. N. Raaschou-Jensen: Financial Interests, Personal, Advisory Board: Merck. L. Gilbert: Financial Interests, Institutional, Other, grants: Alkermes, AstraZeneca, Clovis, Corcept Therapeutics, Esperas, GOG Foundation, GSK, ImmunoGen, IMV, K-Group Beta, Karyopharm, Merck Sharp & Dohme, Mersana Therapeutics, Novocure GmbH, OncoQuest Pharmaceuticals, Roche, Shattuck Labs, Sutro BioPharma, Tesaro; Financial Interests, Personal, Other, consulting fees: GSK, Merck; Financial Interests, Personal, Other, honoraria: CanariaBio, Eisai, Eisai-Merck, GOG Foundation, GSK, ImmunoGen, Kora Healthcare, Merck; Financial Interests, Personal, Other, travel support: EndomEra, GOG Foundation, GSK, Merck, Zentalis; Financial Interests, Personal, Other, participation on a data safety monitoring board or advisory board: CanariaBio, Eisai, Eisai-Merck, GOG Foundation, GSK, Immunogen, Kora Healthcare, Merck. A. Oaknin: Financial Interests, Institutional, Other, grants: AbbVie Deutschland, Advaxis, Aeterna Zentaris, Amgen, Aprea Therapeutics AB, Bristol Myers Squibb, Clovis Oncology, Eisai, F. Hoffmann–La Roche, Immunogen, Merck Sharp & Dohme de España, Millennium Pharmaceuticals, PharmaMar, Regeneron Pharmaceuticals, Tesaro; Financial Interests, Personal, Other, consulting fees: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, F. Hoffmann–La Roche, Genmab, GSK, ImmunoGen, iTeos, Merck Sharp & Dohme de España, Mersana Therapeutics, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Seagen, Shattuck Labs, Sutro Biopharma; Financial Interests, Personal, Other, honoraria: Asociación Colombiada de Ginecológos Oncólogos, AstraZeneca, ESO, GSK, Medscape, NSGO, PeerView, PeerVoice; Financial Interests, Personal, Other, individual travel support: AstraZeneca, PharmaMar, Roche; Financial Interests, Personal, Advisory Board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Eisai, EMD Serono, Exelixis, F. Hoffmann–La Roche, Genmab, GSK, ImmunoGen, iTeos, Merck Sharp & Dohme de España, Mersana Therapeutics, Novocure, OncXerna Therapeutics, PharmaMar, Regeneron, Seagen, Shattuck Labs, Sutro Biopharma. A.A. Secord: Financial Interests, Institutional, Other, presenting an IGCS abstract: GSK; Financial Interests, Institutional, Other, grant support: AbbVie, Aravive, AstraZeneca, Biopharma, Clovis, Eisai, Ellipses, I-Mab, Immunogen, Merck, Oncoquest/Canaria Bio, Roche/Genentech, Seagen, TapImmune, Tesaro/GSK, VBL Therapeutics; Financial Interests, Personal, Other, honoraria: Bio Ascend, Curio Science, GOGFoundation (highlight reel), GOGFoundation Symposium, PeerView, @Point of Care Clinical Care Options, RTP; Financial Interests, Personal, Other, patent issued: "Blood based biomarkers in ovarian cancer“; Non-Financial Interests, Personal, Other, participation on a data safety monitoring board/advisory board: AstraZeneca, Clovis, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova, OncoQuest; Non-Financial Interests, Personal, Leadership Role: AAOGF, NRG, SGO; Financial Interests, Personal, Leadership Role: GOG; Other, Personal, Other, receipt of medical writing support: AstraZeneca; Non-Financial Interests, Personal, Other, clinical trial steering committees: AXLerate trial (Aravive); Non-Financial Interests, Personal, Invited Speaker, clinical trial steering committees: AtTEnd trial (Hoffman-LaRoche), Oval trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), QPT-ORE-004 (CanariaBio). A. Savarese: Financial Interests, Institutional, Other, funding and provision of study materials: GSK, MSD; Financial Interests, Institutional, Other, institutional funding and provision of study material for other clinical trials: GSK, MSD; Financial Interests, Personal, Other, honoraria: GSK, MSK; Financial Interests, Personal, Other, support for attending meetings and/or travel: GSK, MSK, PharmaMar; Financial Interests, Personal, Advisory Board, honoraria: Eisai, MSD. R.W. Holloway: Financial Interests, Personal, Other, honoraria: AstraZeneca, Clovis, Eisai, GSK, Merck. R. Kristeleit: Financial Interests, Personal, Other, grants: Clovis, MSD; Financial Interests, Personal, Other, honoraria and consultancy fees: AstraZeneca, Basilea Pharmaceutica, Clovis, Eisai, Incyte, MSD, PharmaMar; Financial Interests, Personal, Other, personal fees: GSK. J. Buscema: Financial Interests, Personal, Other, honoraria: GSK. I.A. Boere: Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Advisory Board: AstraZeneca, GSK. C. Gennigens: Financial Interests, Personal, Other, grants/contracts: AstraZeneca, GSK; Financial Interests, Personal, Other, consulting fees: GSK, Ipsen, MSD; Financial Interests, Personal, Other, honoraria: AstraZeneca, BMS, Ipsen, MSD, Pfizer, PharmaMar; Other, Personal, Other, support for attending meetings: GSK, Ipsen, MSD, Pfizer, PharmaMar; Other, Personal, Other, participation on a data safety monitoring or advisory board: AstraZeneca, BMS, Eisai, GSK, Ipsen, MSD. K. Yablonski: Other, Personal, Full or part-time Employment: GSK. S. Stevens: Financial Interests, Personal, Full or part-time Employment: GSK. M.A. Powell: Financial Interests, Personal, Other, consulting fees: AstraZeneca, Clovis Oncology, Eisai, GSK, Merck, Seagen, Tesaro. All other authors have declared no conflicts of interest.