Abstract 44TiP
Background
There is an urgent need for new treatments for platinum-resistant recurrent ovarian cancer (PROC). Addition of bevacizumab (bev) to non-platinum-based chemotherapy (chemo) significantly improved PFS in patients (pts) with PROC but did not show a clear OS benefit. Thus far, the combination of paclitaxel + bev has shown the most promise in PROC, although the proportion of pts eligible for bev is limited by treatment-related toxicities. Combination of the anti-PD-1 antibody pembrolizumab (pembro) with weekly paclitaxel showed antitumor activity and manageable toxicity in pts with PROC in a single-arm, phase II study. ENGOT-ov65/KEYNOTE-B96 (NCT05116189) compares the efficacy and safety of pembro + standard of care chemo (weekly paclitaxel) ± bev vs placebo (pbo) + weekly paclitaxel ± bev in pts with PROC.
Trial Design
In this randomized, pbo-controlled, double-blind, phase III study, eligible pts are aged ≥18 y with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1-2 prior lines of systemic therapy, including ≥1 prior platinum-based therapy with ≥4 cycles in first line. Pts must have platinum-resistant disease (radiographic evidence of PD ≤6 mo after last platinum-based therapy dose), be eligible for paclitaxel (± bev per investigator discretion), have ECOG PS ≤1, radiographically evaluable disease per RECIST v1.1, and have a tumor sample for central evaluation of PD-L1 status. ∼616 pts will be randomized 1:1 to pembro 400 mg IV or pbo Q6W for up to 18 cycles (∼2 y) + paclitaxel 80 mg/m2 on days 1, 8, and 15 of each Q3W cycle (± bev 10 mg/kg Q2W per investigator discretion) until PD or unacceptable toxicity. Randomization is stratified by planned bev use (yes vs no), region (US vs Europe vs rest of world), and PD-L1 status (combined positive score [CPS] <1 vs CPS 1-<10 vs CPS ≥10). Primary endpoint is PFS per RECIST v1.1 by investigator review in pts with tumor PD-L1 CPS ≥1 and in all pts. Secondary endpoints are OS in pts with tumor PD-L1 CPS ≥1 and in all pts, PFS per RECIST v1.1 by blinded independent central review in pts with tumor PD-L1 CPS ≥1 and in all pts, safety, and pt-reported outcomes. Enrollment is ongoing.
Clinical trial identification
NCT05116189.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Disclosure
N. Colombo: Financial Interests, Personal, Full or part-time Employment, Employment of Immediate Family Member: Sarepta Therapeutics; Financial Interests, Personal, Advisory Role: Roche/Genentech, AstraZeneca, Clovis Oncology, Pfizer, MSD Oncology, Tesaro, GlaxoSmithKline, Immunogen, Mersana, Eisai, Advaxis, Nuvation Bio, Advaxis; Financial Interests, Personal, Other, Honoraria: Roche/Genentech, AstraZeneca, Tesaro, GlaxoSmithKline, MSD Oncology, Clovis Oncology, Pfizer, Amgen, Immunogen, Novartis, Pfizer, Mersana, Eisai, Advaxis, Nuvation Bio. R.L. Coleman: Financial Interests, Personal, Full or part-time Employment: US Oncology; Financial Interests, Personal, Advisory Role: Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, Tesaro, OncoMed, Sotio, Oncolytics, AbbVie/Stemcentrx, Immunogen, AbbVie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, Regeneron; Financial Interests, Personal, Leadership Role: Onxeo; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck, AstraZeneca/MedImmune, Array BioPharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG Foundation, Sotio, Vaniam Group; Financial Interests, Personal, Stocks/Shares: McKesson; Financial Interests, Personal, Ownership Interest: McKesson; Financial Interests, Personal, Research Grant: AstraZeneca/MedImmune, Esperance Pharmaceuticals, Array Biopharma, Clovis Oncology, Johnson & Johnson, Merck, Roche/Genentech, Abbott/AbbVie; Financial Interests, Institutional, Research Grant: Immunogen, Mirati Therapeutics, Amgen, Pfizer, Lilly, Regeneron. F. Kose: Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen; Financial Interests, Institutional, Other, Honoraria: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, AstraZeneca, MSD/Merck, GlaxoSmithKline, Novartis, Pfizer, Takeda, Deva, Nobel, Astellas, Janssen. R. Wenham: Financial Interests, Personal, Advisory Role: Mersana, Merck, Tesaro, Clovis Oncology, Genentech, Regeneron, AbbVie, AstraZeneca, GlaxoSmithKline, Seattle Genetics/Astellas, Legend Biotech; Financial Interests, Personal, Speaker’s Bureau: Tesaro, Clovis Oncology, Genentech; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: TapImmune Inc; Financial Interests, Personal, Stocks/Shares: Ovation Diagnostics; Financial Interests, Personal, Ownership Interest: Ovation Diagnostics; Financial Interests, Personal, Other, Honoraria: Tesaro, Seattle Genetics; Financial Interests, Institutional, Research Grant: Merck, Prescient Therapeutics, Anixa Biosciences. Other Relationship: AstraZeneca, GlaxoSmithKline/Tesaro; Other, Personal, Other: AstraZeneca, GlaxoSmithKline/Tesaro. A. Sebastianelli: Financial Interests, Personal, Advisory Role: AstraZeneca, Merck, GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Merck, GlaxoSmithKline. K. Hasegawa: Financial Interests, Personal, Advisory Role: MSD K.K., Kaken Pharmaceutical, Eisai, Takeda; Financial Interests, Personal, Other, Honoraria: MSD K.K., Daiichi Sankyo, Chugai Pharma, AstraZeneca, Eisai, Kyowa Kirin, Takeda, Genmab; Financial Interests, Personal, Research Grant: Ono Pharmaceutical, Daiichi Sankyo, Merck, Takeda, Eisai. E. Zsiros: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Other, Honoraria: Survivornet, AstraZeneca, TeneoBio; Financial Interests, Personal, Research Grant: Merck. T. De La Motte Rouge: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, Eisai, French National Cancer Institute (INCa); Financial Interests, Personal, Advisory Role: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, Eisai, French National Cancer Institute (INCa); Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Seagen; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD/Merck, Clovis Oncology, Tesaro, GlaxoSmithKline, Pfizer, Gilead Sciences, French National Cancer Institute (INCa). M. Bidzinski: Financial Interests, Personal, Other, Honoraria: AstraZeneca, MSD/Merck, GlaxoSmithKline, Johnson & Johnson, Olympus. I. McNeish: Financial Interests, Personal, Advisory Role: Clovis Oncology, AstraZeneca, Carrick Therapeutics, Roche, BeiGene, Scancell Ltd., GlaxoSmithKline, Epsila; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca; Financial Interests, Personal, Other, Honoraria: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca. J. Sehouli: Financial Interests, Personal, Advisory Role: AstraZeneca, Clovis Oncology, PharmaMar, Merck, Pfizer, Tesaro, MSD Oncology, Lilly, Novocure, Johnson & Johnson, Roche, Ingress Health, Riemser, Sobi, GlaxoSmithKline, Novartis; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Clovis Oncology, PharmaMar, Roche Pharma AG, Tesaro, MSD Oncology, Olympus; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Eisai, Clovis Oncology, Olympus Medical Systems, Johnson & Johnson, PharmaMar, Pfizer, Teva, Tesaro, MSD Oncology, GlaxoSmithKline, Bayer; Financial Interests, Institutional, Research Grant: AstraZeneca, Clovis Oncology, Merck, Bayer, PharmaMar, Pfizer, Tesaro, MSD Oncology, Roche. J. Korach: Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. P.R. Debruyne: Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Janssen; Financial Interests, Personal, Stocks/Shares: Alkermes, Biocartis Group NV; Financial Interests, Personal, Ownership Interest: Alkermes, Biocartis Group NV; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Merck/Pfizer, MSD, Roche, Bayer. J. Kim: Financial Interests, Personal, Advisory Board: Takeda Korea, GSK Korea, Boryung, Vifor Pharma, MSD Korea; Financial Interests, Personal, Invited Speaker: CMIC, AstraZeneca, Janssen; Financial Interests, Personal, Expert Testimony: LG Pharma. A.C. De Melo: Financial Interests, Personal, Speaker’s Bureau: BMS Brazil, MSD Oncology; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: MSD Oncology; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Novartis, BMS Brazil; Financial Interests, Institutional, Research Grant: Roche, MSD Oncology, BMS Brazil, Novartis, Clovis Oncology, AstraZeneca. X. Peng: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. A.M. Bogusz: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Ownership Interest: Merck & Co., Inc., Kenilworth, NJ, USA. K. Yamada: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Kenilworth, NJ, USA; Financial Interests, Personal, Ownership Interest: Merck & Co., Inc., Kenilworth, NJ, USA. B.J. Monk: Financial Interests, Personal, Advisory Role: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, GOG Foundation, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Myriad Pharmaceuticals, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesa; Financial Interests, Personal, Leadership Role: US Oncology; Financial Interests, Personal, Speaker’s Bureau: Roche/Genentech, AstraZeneca, Clovis Oncology, Eisai, Tesaro/GlaxoSmithKline, Merck; Financial Interests, Personal, Other, Honoraria: Agenus, Akeso Biopharma, Amgen, Aravive, AstraZeneca, Clovis Oncology, Eisai, Genmab/Seattle Genetics, ImmunoGen, Iovance Biotherapeutics, Merck, Mersana, Pfizer, Puma Biotechnology, Regeneron, Roche/Genentech, Tesaro/GlaxoSmithKline, Vascular Biogenics; Financial Interests, Institutional, Research Grant: Novartis, Amgen, Genentech, Lilly, Janssen, Array BioPharma, Tesaro, Morphotek, Pfizer, Advaxis, AstraZeneca, Immunogen, Regeneron, Nucana. All other authors have declared no conflicts of interest.