793TiP - A phase III, randomized, open-label, multicenter study of sacituzumab tirumotecan (sac-TMT) monotherapy vs treatment of physician’s choice chemotherapy in patients with endometrial cancer who have received prior chemotherapy and immunotherapy: ENGOT-en23/GOG-3095/MK-2870-005

Background

Trophoblast cell surface antigen 2 (TROP2) is overexpressed in patients (pts) with endometrial cancer (EC) and is associated with worse prognosis. Sac-TMT (also known as MK-2870/SKB264) is a novel antibody-drug conjugate composed of an anti-TROP2 antibody coupled to a cytotoxic belotecan derivative via a novel linker (average drug/antibody ratio, 7.4). In a phase 1/2 study (KL264-01), IV sac-TMT monotherapy had antitumor activity in pts with previously treated advanced or metastatic solid tumors including TNBC (ORR, 42.4%), HR+/HER2− breast cancer (ORR, 36.8%), and NSCLC (ORR, 38.5%). The current ENGOT-en23/GOG-3095/MK-2870-005 study evaluates sac-TMT monotherapy vs chemotherapy at physician’s choice (TPC) in pts with EC who had received prior chemo and/or anti–PD-(L)1 therapy.

Trial design

This phase 3, randomized, open-label study (NCT06132958) is enrolling pts aged ≥18 y with histologically confirmed endometrial carcinoma or carcinosarcoma, radiographically measurable or nonmeasurable disease per RECIST v1.1 by BICR, ECOG PS ≤1, and tumor tissue available for MMR assessment, TROP2 expression, and histology (central testing). All pts must have received platinum-based chemo and anti–PD-(L)1 therapy, either separately or in combination. Up to 3 prior lines of therapy are allowed. Eligible pts are randomized 1:1 to receive IV sac-TMT 4 mg/kg Q2W or IV TPC (doxorubicin 60 mg/m² Q3W [21-day cycle] or paclitaxel 80 mg/m² on days 1, 8, and 15 Q4W [28-day cycle]) until radiographic PD, unacceptable toxicity, patient withdrawal, or discontinuation criteria are met. Randomization is stratified by MMR status (dMMR vs pMMR), TROP2 expression (low vs medium/high), number of prior lines of therapy (≤2 vs 3), and baseline disease status (measurable vs nonmeasurable). Primary endpoints are PFS per RECIST v1.1 by BICR and OS. Secondary endpoints are ORR and DOR per RECIST v1.1 by BICR, safety, and patient-reported outcomes. Imaging assessments occur Q8W from randomization through week 56 and Q12W thereafter. Enrollment began in Dec 2023.

Clinical trial identification

NCT06132958.

Editorial acknowledgement

Medical writing assistance was provided by Christabel Wilson, MSc, 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

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

D. Lorusso: Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speaker: GSK, Clovis Oncology, PharmaMar; Financial Interests, Personal, Advisory Board, Participation in Advisory Boards and Invited Speakers: AstraZeneca, MSD; Financial Interests, Personal, Other, Consultancy: PharmaMar, AstraZeneca, Clovis Oncology, GSK, MSD, ImmunoGen, Genmab, Seagen, Novartis; Financial Interests, Personal, Advisory Board, Invited member of advisory board and invited speaker: Seagen, ImmunoGen, Genmab; Financial Interests, Personal, Advisory Board, Invited member of advisory board: Oncoinvest, Corcept, Sutro; Financial Interests, Institutional, Funding, Grant for founding academic trials: MSD, Clovis Oncology, GSK, PharmaMar; Financial Interests, Institutional, Coordinating PI, ENGOT trial with institutional support for coordination: Clovis Oncology; Financial Interests, Institutional, Coordinating PI, ENGOT trial with insitutional support for coordination: Genmab, MSD; Financial Interests, Institutional, Funding, Clnical trial/contracted research: AstraZeneca, Clovis Oncology, GSK, MSD, Seagen; Financial Interests, Institutional, Funding, Clinical trials/contracted research: Genmab, ImmunoGen, Incyte, Novartis, Roche; Non-Financial Interests, Principal Investigator, PI of several trials, no compensation received: GSK; Non-Financial Interests, Principal Investigator, PI of several trials. No personal compensation received: AstraZeneca, genmab; Non-Financial Interests, Principal Investigator, PI in several trials. No personal compensation received: MSD; Non-Financial Interests, Principal Investigator, PI of clinical trial. No personal compensation received: immunogen, Clovis Oncology, roche, Incyte; Non-Financial Interests, Principal Investigator, PI of several trials, no personal compensation received: Novartis; Non-Financial Interests, Principal Investigator, PI of clinical trial, no personal compensation received: Seagen; Non-Financial Interests, Principal Investigator, PI of clinical trials, no personal compensation received: PharmaMar; Non-Financial Interests, Member, Board of Directors: GCIG; Other, Grants for traveling: AstraZeneca, Clovis Oncology, GSK. M.R. Mirza: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, Karyopharm, Merck, Zailab, BioNTech, Deiichi Sankyo, Eisai, ImmunoGen/AbbVie, Incyte, Regeneron; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK; Financial Interests, Personal, Member of Board of Directors: Karyopharm; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Institutional, Research Grant: GSK, AstraZeneca, ultimovacs, Apexigen; Financial Interests, Institutional, Trial Chair: Deciphera; Non-Financial Interests, Advisory Role: Ultimovacs; Non-Financial Interests, Member, Member of Prix Galien Awards Committee: Prix Galien Foundation. M.P. Barretina Ginesta: Financial Interests, Personal, Advisory Board: AstraZeneca, GSK, MSD, Eisai, PharmaMar; Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK, MSD, Eisai; Financial Interests, Personal, Steering Committee Member: MSD. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca, Stemline Menarini; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Local PI: Roche, Novartis, Eisai, MSD, Vaccibody, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, Gilead/Immunomedics, German Breast Group, AGO Research GmbH; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. J. Wampfler: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, ExactScience, Gilead, GSK, MSD; Financial Interests, Personal and Institutional, Other, travel support: AstraZeneca, Daiichi Sankyo, ExactScience, Gilead, GSK, MSD. D. Cibula: Financial Interests, Personal, Advisory Board: Roche, Novocure, MSD, GSK, Karyopharm; Financial Interests, Personal, Invited Speaker: AstraZeneca. J. Zhu: Financial Interests, Personal, Advisory Board, As a scientific advisory committee member: Merck. K. Hasegawa: Financial Interests, Personal, Invited Speaker: MSD, AstraZeneca, Takeda, Chugai, Genmab, Kaken, Eisai, Sanofi; Financial Interests, Personal, Advisory Board: GSK, Daiichi Sankyo, Terumo; Financial Interests, Institutional, Funding, contracted research: MSD, Ono, Daiichi Sankyo, Eisai, Takeda. V. Samouëlian: Financial Interests, Personal, Advisory Board, Consultant: Merck, GSK, AstraZeneca, EIsai. J. Lee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda, MSD, Roche; Financial Interests, Personal, Advisory Board: Eisai, GI Innovation; Financial Interests, Institutional, Local PI: Alkermes, AstraZeneca, BergenBio, Cellid, Clovis Oncology, Eisai, GI Innovation, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, OncoQuest, Roche, Seagen, Synthon; Financial Interests, Personal and Institutional, Local PI: Beigene; Financial Interests, Personal, Steering Committee Member: AstraZeneca, OncoQuest, Seagen, ImmunoGen, MSD; Financial Interests, Institutional, Research Grant: ONO, Takeda. F.C. Casarotto: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, Merck Serono; Financial Interests, Personal, Speaker’s Bureau: MSD, AstraZeneca, GSK, Beyer; Financial Interests, Personal, Other, Investigator in clinical trials: MSD; Financial Interests, Personal, Other, travel and accommodation support: GSK, Merck Serono, Beyer. Y. Antill: Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, GSK, Eisai; Financial Interests, Personal, Speaker’s Bureau: MSD, AstraZeneca, GSK, Eisai; Financial Interests, Personal, Research Funding: AstraZeneca. T.J. Herzog: Financial Interests, Personal, Advisory Board: J & J, Clovis, AstraZeneca, GSK, Roche Genentech, Caris, Merck, Eisai, Seagen, Mersana, ImmunoGen, and Aadi; Financial Interests, Personal, Other, DSMB: Corcept. K. Woodhouse: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. Y. Cui: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA ; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. B.M. Slomovitz: Financial Interests, Personal, Advisory Board: AstraZeneca, Eisai, GSK, Genentech, Merck, ImmunoGen, Novocure, Aadi, Seagen, Incyte; Non-Financial Interests, Member of Board of Directors: GOG Foundation. B.J. Monk: Financial Interests, Personal, Other, Consultant: Agenus, Elevar, GOG Foundation, Genmab/Seattle Genetics, Gradalis, ImmunoGen, Karyopharm, Mersana, Novocure, Pfizer, Acrivon, Alkemers, Amgen, Bayer, BioNtech, Corcept, Duality, EMD Merck, Genalux, Laekna, Novartis, OncoC4, Panavance, Profound Bio, Sarah Cannon Research Institue, Tubulis; Financial Interests, Personal, Other, Consultant/Speaker: AstraZeneca, Clovis, Easai, Merck, Myriad, Roche/Genentech, Tesaro/GSK; Financial Interests, Personal, Other, Honorarium Consultant: Regeneron, Verastem, Zentalis; Financial Interests, Personal, Invited Speaker: Aadi; Financial Interests, Personal, Other, Speaker/Consultant: Adaptimune. All other authors have declared no conflicts of interest.