126TiP REJOICE-Ovarian02: A phase Ib/II study of raludotatug deruxtecan (R-DXd) with other anticancer agents in participants (pts) with relapsed ovarian cancer (OC) after platinum-based chemotherapy

Abstract

Background: Most patients with OC have disease recurrence after treatment with the current standard of care, highlighting the need for new therapies. R-DXd is an antibody-drug conjugate targeting cadherin-6 (CDH6), which is overexpressed in several tumor types, including OC. R-DXd consists of a humanized anti-CDH6 antibody, an enzymatically cleavable peptide linker, and a cytotoxic topoisomerase I inhibitor (target drug-to-antibody ratio, 8). In a first-in-human study (NCT04707248), R-DXd monotherapy showed promising antitumor activity and manageable safety in pts with recurrent OC. Herein, we describe the phase Ib portion of a phase Ib/2, open-label, dose-escalation study (REJOICE-Ovarian02; NCT06843447) to assess safety, tolerability, and preliminary antitumor activity of R-DXd combined with carboplatin or paclitaxel in pts with platinum-sensitive recurrent OC (PSOC) or with bevacizumab in pts with platinum-resistant recurrent OC (PROC). Trial Design: The phase Ib portion is enrolling ~78 pts with high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer who have relapsed disease after 1-3 prior lines of therapy and had progressed >=6 mo (PSOC) or <6 mo (PROC) after the last dose of platinum-based therapy. Pts have measurable disease per RECIST v1.1, ECOG PS of 0 or 1, and adequate organ function. Pts with primary platinum-refractory OC are ineligible. Pts with PSOC receive R-DXd + carboplatin (cohort A-1 arm 1) or paclitaxel (cohort A-1 arm 2). Pts with PROC receive R-DXd + bevacizumab (cohort B-1). Dose escalation is done to determine the maximum tolerated dose based on dose-limiting toxicities (DLTs) using the Bayesian optimal interval design. Treatment with R-DXd or R-DXd + bevacizumab continues until disease progression, unacceptable toxicity, pt withdrawal, or another discontinuation criterion is met. Primary endpoints are DLTs, AEs, and treatment discontinuations due to AEs. The secondary endpoint is ORR. Enrollment is ongoing. Clinical trial identification: Protocol MK-5909-003 (approval date, October 23, 2024); NCT06843447; EudraCT 2024-514674-47. Editorial acknowledgement: Medical writing assistance was provided by Tina Nie, PhD, of ICON plc (Blue Bell, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Legal entity responsible for the study: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Funding(s): Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Disclosure: A. Oaknin: Financial Interests, Personal, Other, Consulting fees: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daiichi Sankyo, Debiopharm International, Eisai, Exelisis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen-Pfizer, Sutro Biopharma, TORL Therapeutics, Zentalis, and Zymeworks; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, or manuscript writing: Peerview, Peervoice, Medscape, AstraZeneca, and GSK; Financial Interests, Personal, Other, Support for attending meetings or travel: AstraZeneca, PharmaMar, and Roche; Financial Interests, Personal, Other, participation on a data safety monitoring board or advisory board: Agenus, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daiichi Sankyo, Debiopharm International, Eisai, Exelisis, F Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics, PharmaMar, Regeneron, Sattucklabs, Seagen-Pfizer, Sutro Biopharma, TORL Therapeutics, Zentalis, and Zymeworks; Financial Interests, Personal, Other, leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Gynecologic Cancer Intergroup and European Society for Medical Oncology; Financial Interests, Personal, Other, other financial or non-financial interests: Gynecologic Cancer Intergroup, European Society for Medical Oncology, American Society of Clinical Oncology, Spanish Society of Medical Oncology, and GOG Foundation. R. Shapira-Frommer: Financial Interests, Personal, Other, Honoraria: MSD Oncology, Bristol Myers Squibb, Novartis, Roche, AstraZeneca, Medison, Neopharm, and MSD; Financial Interests, Institutional, Other, Honoraria: MSD; Financial Interests, Personal, Advisory Board: Vascular Biogenics, Clovis Oncology, and MSD Oncology. O.S. Rosengarten: Financial Interests, Personal, Other, Honoraria: MSD, Bristol Myers Squibb, Novartis, Pfizer, AstraZeneca, Medison, GSK, Neopharm Israel, and Rafa Israel; Financial Interests, Institutional, Other, Donations: AstraZeneca, Novartis, Eli Lilly, and MSD; Financial Interests, Personal, Advisory Board: Vascular Biogenics, MSD Oncology, AstraZeneca, Neopharm, GSK, and Rafa Israel. R. Perets: Financial Interests, Personal, Other, honoraria: AstraZeneca, GSK, and Neopharm; Financial Interests, Personal, Other, consulting fees: MSD, Galmed, Clexio, Simplivia, Nevia Bio, and Third Arc Bio. A. Gonzalez-Martin: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, AstraZeneca, AbbVie, Clovis, Daiichi Sankyo, Eisai, Genmab, GSK, HederaDx, Illumina, InmunoGen, Karyopharm, Mersana, MSD, Macrogenics, Novartis, Oncoinvent, PharmaMar, pharma&, Roche, Regeneron, Sotio, Sutro, Seagen, Sotio, Tubulis, BioNTech, TORL; Financial Interests, Personal, Invited Speaker: AstraZeneca, Clovis, GSK, Karyopharm, MSD, Novocure, Roche, Takeda, Zaylab, AbbVie; Financial Interests, Institutional, Invited Speaker, PI of ANITA trial: GSK, Roche; Financial Interests, Personal, Invited Speaker, Member of ENGOT ov43-SC: MSD; Financial Interests, Institutional, Invited Speaker, ENGOT PI of EPIK-O trial: Novartis; Financial Interests, Institutional, Invited Speaker, ENGOT PI of AVB-500 phase III trial: ARAVIVE; Financial Interests, Personal, Invited Speaker, Global PI of TroFuse-022/ENGOT-ov84/GOG-3103: MSD; Financial Interests, Personal, Invited Speaker, Global PI for DESTINY-OVARIAN-01/ ENGOT-ov89: Daiichi Sankyo; Non-Financial Interests, Personal, Member of Board of Directors, President: GEICO (Grupo Espanol de Investigacion en Cancer ginecologicO). M. Gil Martin: Financial Interests, Personal, Other, honoraria for speaking: MSD and AstraZeneca; Financial Interests, Personal, Other, support for attending scientific meetings and travel: MSD, Clovis, GSK, and AstraZeneca; Financial Interests, Personal, Advisory Board, consulting or advisory: AstraZeneca. L. Manso Sanchez: Financial Interests, Personal, Other, consulting fees: AstraZeneca, pharma&, Genmab, GSK, MSD, Novartis, Roche, and Seagen; Financial Interests, Personal, Other, payment or honoraria: AstraZeneca, GSK, MSD, and Roche; Financial Interests, Personal, Other, support for attending meetings and/or travel: AstraZeneca, GSK, MSD, and Roche. L. Gilbert: Financial Interests, Institutional, Research Grant, grants or contracts: IMV, Pfizer, Sutro Bio Pharma, MSD, Corcept Therapeutics, ImmunoGen, Shattuck Labs, Roche, Tesaro, K-Group Beta Inc., GOG Foundation, GSK, AstraZeneca, OncoQuest Pharmaceuticals, Novocure GmbH, Alkermes Inc., Espersas, Mersana, Ascendis, Bayer, CanariaBio, Daiichi Sankyo, Eisai, Fortrea, Karyopharm, Parexel, Pri-Wex Pharma, Repare, Seagen, and Sichuan Kelun Biopharma/Parexel; Financial Interests, Personal, Other, consulting fees: MSD and GSK; Financial Interests, Personal, Other, payment or honoraria: MSD, GSK, and Repare; Financial Interests, Personal, Other, support for attending meetings and/or travel: GSK, MSD, EndomERA, and Zentalis; Financial Interests, Personal, Advisory Board: GSK, MSD, Eisai, Novocure, Kora Health, Corcept, ImmunoGen, and Canariabio Inc. R. Redman: Financial Interests, Institutional, Research Grant, grants or contracts: MSD, Coherus BioSciences, Dragonfly Therapeutics, and RAPT Therapeutics. R. Kristeleit: Financial Interests, Personal, Advisory Board, consultancy or advisory board: pharma&, DukeStreetBio, Merck AG, Tubulis, Leucid Bio, Prokarium, AstraZeneca, GSK, InCyte, Eisai, MSD, GenMab, ImmunoGen, and AbbVie; Financial Interests, Personal, Other, travel support: Epsilogen. R. Miller: Financial Interests, Personal, Other, consultancy: MSD, GSK, AstraZeneca, Ellipses, Shionogi, Clovis Oncology, AbbVie, pharma&, and GI Innovation; Financial Interests, Personal, Speaker's Bureau: GSK, AstraZeneca, Eisai, pharma&, MSD, AbbVie, and Clovis Oncology; Financial Interests, Personal, Other, travel grants: AstraZeneca, MSD, pharma&, and GSK; Financial Interests, Personal, Funding, trial funding: MSD and GSK. S. Banerjee: Financial Interests, Personal, Other, consulting fees: AbbVie, AstraZeneca, BeiGene, BioNTech, Eisai, Gilead, GSK, Grey Wolf Therapeutics, ImmunoGen, Incyte, ITM Oncologics, Lilly, MSD, Mersana, Myriad, Oncxerna, pharma&, Seagen, TORL BioTherapeutics, Verastem, and Zymeworks; Financial Interests, Personal, Other, support to attend meetings: AstraZeneca, Lilly, Verastem, and Zymeworks; Financial Interests, Institutional, Funding: AstraZeneca and GSK; Financial Interests, Personal, Other, leadership role (unpaid): Gynecologic Cancer Intergroup, European Society for Medical Oncology, and Royal Society of Medicine; Financial Interests, Personal, Other, honoraria: AbbVie, AstraZeneca, GSK, ImmunoGen, MSD, Mersana, Takeda, Verastem, and Zymeworks. S. Lheureux: Financial Interests, Personal, Other, grants or contracts: AstraZeneca, GSK, Roche, Repare Therapeutics, MSD, and Seagen; Financial Interests, Personal, Other, consulting fees: Roche, GSK, AstraZeneca, MSD, Schrodinger, and Seagen; Financial Interests, Personal, Other, payment or honoraria: GSK and AstraZeneca; Financial Interests, Personal, Advisory Board, participation on data safety monitoring boards or advisory boards: AstraZeneca, GSK, Repare Therapeutics, Seagen, and Eisai. Q. Zhao: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. S. Re: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo, Inc.; Financial Interests, Personal, Stocks/Shares: Daiichi Sankyo, Inc. C. Gonzalez Arenas: Financial Interests, Personal, Full or part-time Employment: MSD, Madrid, Spain; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. D.L. Richardson: Financial Interests, Personal, Advisory Board: Mersana Therapeutics, Daiichi Sankyo, Genmab, Repare Therapeutics, GSK, Incyte, ImmunoGen, Eisai, AbbVie; Financial Interests, Personal, Invited Speaker: Zentalis; Financial Interests, Personal and Institutional, Invited Speaker, Also PI for US: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Genmab, Mersana Therapeutics, GSK, Hookipa Biotech, ImmunoGen/AbbVie, Acrivon, PMV Pharmaceuticals, Xencor, Nurix, Duality Bio, Allorian, A2A Pharmaceuticals, OnCusp; Financial Interests, Institutional, Invited Speaker, Also local PI of trial: Karyopharm; Non-Financial Interests, Personal, Member of Board of Directors: SGO, NOCC. All other authors have declared no conflicts of interest. Copyright © 2025