Abstract 145P
Background
First-line pembro + gem/cis significantly increased OS vs placebo (pbo) + gem/cis for patients (pts) with advanced BTC (HR, 0.83; 95% CI, 0.72-0.95; P=0.0034) in the phase III KEYNOTE-966 study. This post hoc analysis assessed whether patient HBV infection status was associated with differences in efficacy and safety outcomes.
Methods
Pts were randomly assigned 1:1 to pembro 200 mg IV or pbo IV Q3W for ≤35 cycles + gem 1000 mg/m2 IV until PD and cis 25 mg/m2 IV for ≤8 cycles. HBV status was determined by anti-HBc (total and IgM), HBV DNA, and HBsAg. Pts with chronic HBV infection (HBsAg positive and/or detectable HBV DNA) and clinically resolved HBV infection (HBsAg negative and anti-HBc positive and undetectable HBV DNA) at baseline were eligible (HBV-positive subgroup). Pts with chronic HBV infection needed to have begun antiviral therapy ≥4 weeks before and had HBV DNA <100 IU/mL before starting study treatment. The database cutoff was Nov 14, 2023.
Results
Overall, 1069 pts were enrolled in KEYNOTE-966. At baseline, 329 pts (30.8%) were HBV positive (pembro, n = 164; pbo, n = 165) and 732 pts (68.5%) were HBV negative (n = 366 from each arm); 8 pts (0.7%) had unknown HBV status at baseline. In the HBV-positive subgroup, the OS HR was 0.87 (95% CI 0.69-1.10). For the HBV-negative subgroup, the OS HR was 0.85 (95% CI 0.73-0.99). Grade 3-5 treatment-related adverse events (AEs) occurred at similar rates in the HBV-positive subgroup (pembro, 69%; pbo, 73%) and the HBV-negative subgroup (pembro, 72%; pbo, 68%). Treatment-related AEs resulted in discontinuation of any drug at similar rates in the HBV-positive subgroup (pembro, 14%; pbo, 15%) and the HBV-negative subgroup (pembro, 22%; pbo, 16%).
Conclusions
Efficacy and safety outcomes remained consistent between HBV-positive and HBV-negative subgroups from KEYNOTE-966. These data further support first-line pembro + gem/cis for advanced BTC regardless of HBV infection status, with careful monitoring and antiviral therapy required for patients with baseline HBV infection. ©2024 ASCO, 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 Shane Walton, PhD, CMPP, 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
T. Yau: Financial Interests, Personal, Other, Honoraria: AstraZeneca; Bristol Myers Squibb; MSD Oncology; Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb. 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. 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. R.S. Finn: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; Bayer; Bristol Myers Squibb; CStone Pharmaceuticals; Eisai; Exelixis; Genentech/Roche; Hengrui Therapeutics; Lilly; Medivir; 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; Roche/Genentech; Servier; Financial Interests, Personal, Research Funding: AstraZeneca; Bayer; Boryung Pharmaceuticals; CKD pharm; Eisai; Lunit; Servier. 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. Z. Ren: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca; GSK; MSD; Roche; Financial Interests, Institutional, Research Funding: MSD. H.J. Klumpen: Financial Interests, Institutional, Speaker, Consultant, Advisor: AstraZeneca; Janssen; Financial Interests, Institutional, Research Funding: Bayer; Bristol Myers Squibb; Exelixis; Incyte; Ipsen; ITM Solucin; MSD/Merck; Roche; Taiho Pharmaceutical. M. Ozaka: Financial Interests, Personal, Invited Speaker: Taiho, Yaklut, MSD, Incyte, Ono, Bayer, Servier. C. Arslan: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Merck, AstraZeneca, Johnson &Johnson, Teva, Astellas, BMS, Amgen, Bayer; Financial Interests, Personal, Speaker’s Bureau: Novartis, Merck, AstraZeneca, Johnson &Johnson, Teva, Astellas, BMS, Amgen, Bayer; Financial Interests, Personal, Research Funding: Roche, Novartis, BMS, Merck, MSD, AstraZeneca, Nektar, Johnson &Johnson, Lilly, Amgen, Incyte, Bayer, Yuhan, Henlius, Pfizer, BioNTech, Genmab, Beigene, GSK. 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. 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. J.W. Valle: Financial Interests, Personal, Advisory Board: Astra-Zeneca, 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. 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. 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. L. Starkopf, U. Malhotra, A.B. Siegel: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co., Inc. All other authors have declared no conflicts of interest.