133MO - Pembrolizumab (pembro) plus gemcitabine and cisplatin (gem/cis) compared with gem/cis alone for patients (pts) with advanced biliary tract cancer (BTC): Updated efficacy and safety from KEYNOTE-966

Background

BTC is an aggressive malignancy with a poor prognosis. In KEYNOTE-966, adding pembro to gem/cis provided a statistically significant, clinically meaningful improvement in OS as first-line therapy for BTC (median 12.7 mo vs 10.9 mo with placebo + gem/cis; HR 0.83 [95% CI 0.72-0.95]; P = 0.0034). Here, we provide efficacy and safety data with an additional 4 mo follow-up (39 additional OS events).

Methods

Adults with previously untreated, histologically confirmed, metastatic or unresectable locally advanced BTC were randomized 1:1 to pembro 200 mg or placebo Q3W for ≤35 cycles plus 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 in the intent-to-treat population. Secondary end points were PFS, ORR, and DOR (all as assessed by blinded independent central review per RECIST v1.1), and safety. The data cutoff date was April 13, 2023.

Results

1,069 pts were randomized to pembro + gem/cis (n = 533) and placebo + gem/cis (n = 536). Based on a median follow-up duration (ie, time from randomization to data cutoff) of 29.5 mo, there remained a significant difference in OS between both groups (HR 0.84, 95% CI 0.74-0.96). Median OS was 12.7 mo (95% CI 11.5-13.6) for pembro + gem/cis and 10.9 mo (95% CI 9.9-11.6) for placebo + gem/cis; respective 24-month survival estimates were 24.7% and 19.1%. OS in key subgroups were consistent with the final analysis. Safety profiles were comparable, with 377 (71.3%) pts in the pembro + gem/cis group having grade 3-5 treatment-related AEs (TRAEs) vs 370 (69.3%) in the placebo + gem/cis group, and there were no additional deaths since the final analysis. 40 (7.6%) pts receiving pembro + gem/cis had grade 3-5 immune-mediated AEs and infusion reactions vs 21 (3.9%) with placebo + gem/cis.

Conclusions

With a median follow-up of 29.5 mo, pembro + gem/cis continued to demonstrate clinically meaningful OS improvement and no new safety signals compared with placebo + gem/cis in pts with unresectable or advanced BTC.

Clinical trial identification

NCT04003636, first posted July 1, 2019.

Editorial acknowledgement

Editorial assistance provided by David K Edwards V, PhD, CMPP, an employee of 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

R.S. Finn: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, BMS, CSTONE, Eisai, Exelixis, Eli LIlly, Merck, Pfizer, Roche, Genentech, Hengrui; Financial Interests, Personal, Invited Speaker: Pfizer, Roche, Bayer; Financial Interests, Institutional, Research Grant: Bayer, Eisai, Eli Lilly, BMS; Financial Interests, Institutional, Coordinating PI: Roche, Pfizer, Merck. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical, Daiichi Sankyo, Takeda Pharmaceutical; 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. C. Yoo: Financial Interests, Personal, Invited Speaker: Bayer, Celgene, Eisai, Ipsen, Servier, Roche, Novartis; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Research Grant: AstraZeneca, Bayer, Servier; Financial Interests, Institutional, Research Grant: Genentech. Z. Ren: Financial Interests, Institutional, Research Funding: Merck & Co., Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, AstraZeneca, Roche ; Financial Interests, Personal, Invited Speaker: Bayer, MSD, Roche. 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, Institutional, Research Funding: Merck & Co., Inc.; Financial Interests, Personal, Advisory Board: MSD, Compass Therapeutics, Kinnate, Exact Sciences, Regeneron, and Tyra Biosciences; Financial Interests, Institutional, Research Grant: Agios, AstraZeneca, Bayer, BMS, Eli Lilly, EMD Serono, Genentech/Roche, Loxo Oncology, MSD, Novartis, Partner Therapeutics, QED, Relay Therapeutics, Surface Oncology, and Taiho; Financial Interests, Institutional, Advisory Board: Agios, AstraZeneca, Exelixis, Ipsen, and MSD; Financial Interests, Personal, Other: MSD, AstraZeneca. S.L. Chan: Financial Interests, Personal, Advisory Board: Eisai, AstraZeneca, MSD, BMS, Roche; Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD, Eisai, Roche, Ipsen, BMS; 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, Personal, Speaker, Consultant, Advisor: Servier, Bayer, AstraZeneca, MSD, Eisai, Celgene, Bristol Myers Squibb, Debiopharm, Ipsen, Kyowa Kirin, Novartis, Boryung Pharmaceuticals, Merck Serono, Mundipharma, Roche, and Janssen; Financial Interests, Personal, Research Grant: Servier, Bayer, AstraZeneca, MSD, Eisai, Celgene, Bristol Myers Squibb, Debiopharm, Ipsen, Kyowa Kirin, Novartis, Boryung Pharmaceuticals, Merck Serono, Mundipharma, Roche, and Janssen. T. Yau: Financial Interests, Institutional, Research Funding: Merck & Co., Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, MSD, AstraZeneca, Eisai, and Ipsen; Financial Interests, Personal, Other: Roche, Bayer; Financial Interests, Personal, Stocks/Shares: Moderna. M. Ozaka: Financial Interests, Personal, Invited Speaker: Taiho, Yaklut, MSD, Incyte, Ono, Bayer, Servier. J.G. Kim: Financial Interests, Institutional, Research Funding: Merck & Co., Inc. 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 Ingelheim, Eisai, INCYTE, Ipsen, Janssen, MSD, Pierre Fabre, Roche, Servier, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Ipsen, Lilly, MSD, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. J.W. Valle: Financial Interests, Institutional, Research Funding: Merck & Co., Inc.; Financial Interests, Personal, Speaker, Consultant, Advisor: Ipsen, Novartis, AstraZeneca, Merck, Pfizer, PCI Biotech, Incyte, Keocyt, QED Therapeutics, Pieris Pharmaceuticals, Genoscience Pharma, Mundipharma, Wren Laboratories, Nucana, Debiopharm Group, Imaging Equipment Limited, Hutchison MediPharma, Zymeworks, A; Financial Interests, Personal, Speaker’s Bureau: Novartis, Ipsen, Nucana, Imaging Equipment Limited, Mylan, Incyte, Servier, and Delcath Systems; Financial Interests, Personal, Other: Nucana, Lilly, Roche, and AstraZeneca/MedImmune. L. Yu, U. Malhotra, A.B. Siegel: Financial Interests, Personal, Full or part-time Employment: Merck & Co., Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc. All other authors have declared no conflicts of interest.