139P - KEYNOTE-966: 3-year follow-up for pembrolizumab (pembro) + gemcitabine and cisplatin (gem/cis) vs placebo (pbo) + gem/cis for patients (pts) with advanced biliary tract cancer (BTC)

Background

After a median follow-up of 25.6 months, pembro + gem/cis provided a statistically significant and clinically meaningful improvement in OS vs placebo + gem/cis (median, 12.7 mo vs 10.9 mo; HR, 0.83 [95% CI, 0.72-0.95]; P=0.0034) in the KEYNOTE-966 study (NCT04003636). Here, we report outcomes after an additional 11 mo of follow-up.

Methods

Patients (pts) aged ≥18 years with previously untreated histologically confirmed metastatic or unresectable locally advanced BTC measurable per RECIST v1.1 and with ECOG PS 0 or 1 were eligible. Pts were randomly assigned 1:1 to pembro 200 mg or pbo Q3W for ≤35 cycles + gem 1000 mg/m² on days 1 and 8 Q3W until PD and cis 25 mg/m² on days 1 and 8 for ≤8 cycles. Pts were stratified by region (Asia vs non-Asia), stage (locally advanced vs metastatic), and site of origin (gallbladder vs intrahepatic vs extrahepatic). The primary end point was OS; secondary end points were PFS, ORR, and DOR per RECIST v1.1 by BICR and safety. The data cutoff date was Nov 14, 2023.

Results

A total of 1069 pts were randomly assigned to pembro + gem/cis (n = 533) or pbo + gem/cis (n = 536). Median follow-up was 36.6 mo (range, 29.2-49.4). Efficacy is reported in the table; OS was maintained with longer follow-up. OS in key subgroups continued to favor the pembro arm. Grade 3-5 treatment-related adverse events (AEs) occurred in 378 (71.5%) of 529 treated pts in the pembro arm vs 370 (69.3%) of 534 treated pts in the pbo arm. There were no additional treatment-related deaths since the final analysis. Table: 139P

^aFrom product-limit (Kaplan-Meier) method for censored data.

Conclusions

With a median follow-up of 36.6 mo, the clinically meaningful OS benefit with pembro + gem/cis was maintained with no new safety signals compared to pbo + gem/cis in pts with unresectable or advanced BTC. ©2024 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2024 ASCO Annual Meeting. All rights reserved.

Clinical trial identification

NCT04003636.

Editorial acknowledgement

Medical writing assistance was provided by Bresler Swanepoel, PhD, and Holly C. Cappelli, PhD, CMPP of ApotheCom (Yardley, PA, USA) and 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

M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical, J-pharma, Eisai, Yakult Honsha; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Local PI: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis, J-pharma, Novocure, Chiome Bioscience. R.S. Finn: Financial Interests, Personal, Advisory Role: AstraZeneca, Bayer, Bristol Myers Squibb, CStone Pharmaceuticals, Eisai, Exelixis, Genentech/Roche, Hengrui Therapeutics, Lilly, Merck, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Genentech; Financial Interests, Institutional, Research Funding: Bayer, Bristol Myers Squibb, Eisai, Lilly, Merck, Novartis, Pfizer, Roche/Genentech. C. Yoo: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bayer, Boryung Pharmaceuticals, Bristol Myers Squibb, Celgene, Eisai, Ipsen, MSD Oncology, Novartis, Servier; Financial Interests, Personal, Research Funding: AstraZeneca, Bayer, Servier. Z. Ren: Financial Interests, Personal, Advisory Role: AstraZeneca, BeiGene, F. Hoffmann LaRoche, Innovent Biologics, Merck Sharp & Dohme. J. Furuse: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical, Bayer, Eisai, Eli Lilly Japan, MSD, Yakult Honsha, Chugai Pharma, Novartis Pharma, AstraZeneca, Pfizer, Takeda, Taiho Pharmaceutical, Sannofy, Mylan EPD, EA Pharma, Kyowa Hakko Kirin, Daiichi Sankyo, Teijin pharma, Servier Japan, Incy; Financial Interests, Personal, Advisory Board: Fuji film, Mudi Pharma, Onco Therapy Science, Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Chugai Pharma, Astellas, AstraZeneca, Takara bio, Delta-Fly-Pharma, Incyte Japan; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical, MSD, Merck Bio, J-Pharma, Taiho Pharmaceutical, Takeda, Chugai Pharma, AstraZeneca, Yakult Honsha, Eisai, Daiichi Sankyo, Mochida, Sanofy, Sumitomo Dainippon Bayer, Astellas, Incyte Japan; Financial Interests, Personal, Steering Committee Member: Merck Bio, Ono Pharmaceutical, MSD, Taiho Pharmaceutical, Astellas, AstraZeneca, Incyte Japan. R.K. Kelley: Financial Interests, Personal, Advisory Board, Compensation for service on advisory board in 2019: Genentech/Roche; Financial Interests, Personal, Other, IDMC membership 2018-2020: Genentech/Roche; Financial Interests, Personal, Advisory Board, 2020: Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board, Advisory board member in 2021: Kinnate; Financial Interests, Personal, Advisory Board, Ad Board late 2022: Regeneron; Financial Interests, Personal, Advisory Board, GI ASCO 2023 Ad Board: Tyra Biosciences; Financial Interests, Personal, Advisory Board, Ad board around GI ASCO 2023: Compass Therapeutics; Financial Interests, Institutional, Steering Committee Member: Agios, AstraZeneca, Merck; Financial Interests, Institutional, Local PI: Agios, AstraZeneca, BMS, Eli Lilly, EMD Serono, Genentech/Roche, Merck, QED, Taiho, Novartis, Relay Therapeutics, Surface Oncology, Loxo Oncology, Compass; Financial Interests, Institutional, Coordinating PI: Bayer, Exelixis, AstraZeneca, Merck, Servier, Tyra Biosciences; Financial Interests, Institutional, Research Grant: Partner Therapeutics; Non-Financial Interests, Personal, Advisory Role, IDMC chair and member: Genentech/Roche; Non-Financial Interests, Personal, Principal Investigator: Exelixis, AstraZeneca; Non-Financial Interests, Personal, Advisory Role, IDMC member: Merck. S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eisai, Roche, Ipsen; Financial Interests, Personal, Research Grant: Eisai, MSD. J. Edeline: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, MSD, Bayer, Boston Scientific, Eisai, Ipsen, Servier; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Bayer, Merck Serono, Eisai, Ipsen, BMS, Basilea, Servier, Incyte, Beigene, Taiho; Financial Interests, Personal, Steering Committee Member: MSD; Financial Interests, Institutional, Coordinating PI: BMS, Beigene; Financial Interests, Institutional, Local PI: BMS, MSD, Roche, Beigene, Bayer, Novartis, Taiho, Servier, Agios; Non-Financial Interests, Personal, Principal Investigator: Unicancer. H.J. Klumpen: Financial Interests, Institutional, Advisory Role: AstraZeneca, Janssen Oncology ; Financial Interests, Institutional, Speaker’s Bureau: Ipsen, Medtalks. C.C. Yau: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, MSD Oncology; Financial Interests, Personal, Advisory Role, Honoraria: Bristol Myers Squibb. C. Verslype: Financial Interests, Personal, Advisory Board: Roche, Bayer, MSD; Financial Interests, Personal, Invited Speaker: Ipsen, Bayer; Financial Interests, Institutional, Research Grant, unrestricted: Bayer; Non-Financial Interests, Personal, Member, Lobby group: Pancreatic Cancer Europe. M. Ozaka: Financial Interests, Personal, Invited Speaker: Taiho, Yaklut, MSD, Incyte, Ono, Bayer, Servier. M. Bouattour: Financial Interests, Personal, Advisory Board: MSD, BMS, SIRTEX Medical, Ipsen, AbbVie, AstraZeneca, Servier, Taiho; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Principal Investigator: MSD, BMS, SIRTEX Medical, AstraZeneca. J.O. Park: Financial Interests, Personal, Advisory Board: MedPacto, BMS (Celgene), Servier, MediRama, Adicet Bio, AstraZeneca, Merck Sereno, ImmuneOncia, Merck; Financial Interests, Personal, Other, Travel support for a poster presentation at ASCO GI 2023: Minneamrita Therapeutics LLC; Financial Interests, Personal, Research Grant, Clinical research grant: MedPacto, Servier, BMS (Celgene); Financial Interests, Personal, Research Grant: Eutilex, ABL Bio. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Boehringer Mannheim, Eisai, Incyte, Ipsen, MSD, Roche, Servier, Tyra, Taiho, AbbVie; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, MSD, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Roche, MSD, Beigene, Boehringer Ingelheim. J.W. Valle: Financial Interests, Personal, Advisory Board: AstraZeneca, Agios, QED, NuCana BioMed, Servier, Image Equipment Ltd (AAA), Hutchinson Medipharma, Zymeworks, Sirtex, Baxter, Autem, Hutchinson Medipharma; Financial Interests, Personal, Invited Speaker: Ipsen, Mylan, Incyte; Financial Interests, Institutional, Research Grant, Grant funding for ABC-12 study: AstraZeneca; Financial Interests, Institutional, Research Grant, University of Manchester: RedX. L. Starkopf, U. Malhotra, A.B. Siegel: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc. All other authors have declared no conflicts of interest.