100P - Hepatitis B virus (HBV)-related outcomes in patients (pts) with baseline HBV infection in the KEYNOTE-966 study of pembrolizumab (pembro) plus gemcitabine and cisplatin (gem/cis) for advanced biliary tract cancer (BTC)

Background

Pembro + gem/cis significantly improved OS versus placebo (pbo) + gem/cis as 1L therapy for unresectable or metastatic BTC in KEYNOTE-966 (NCT04003636). Pembro monotherapy had limited impact on underlying HBV infection in advanced HCC. The effect of chemoimmunotherapy on underlying HBV in pts with cancer is unknown. We characterized HBV-related outcomes in pts with HBV enrolled in KEYNOTE-966.

Methods

Pts were randomized 1:1 to pembro 200 mg or pbo Q3W for ≤35 cycles plus gem/cis. Pts with clinically resolved HBV infection (ie, HBsAg negative, anti-HBc positive, and HBV DNA <20 IU/mL) were eligible. Pts with chronic HBV infection (ie, HBsAg positive or HBV DNA ≥20 IU/mL) were eligible if antiviral therapy was started ≥4 wk before study therapy if HBV DNA was >100 IU/mL. HBV DNA and HBsAg were assessed every 6 wk in pts with undetectable HBV DNA at baseline (BL) not taking HBV therapy and every 12 wk in pts taking HBV therapy. Pts with HBV DNA >100 IU/mL were to start HBV treatment. Pts on HBV therapy at BL were to stay on same therapy throughout the study. HBV reactivation and HBV-associated hepatitis were defined per AASLD criteria.

Results

164 (30.8%) of 533 pts in the pembro arm and 165 (30.8%) of 536 in the pbo arm had BL HBV infection, including 150 (28.1%) and 149 (27.8%) with clinically resolved and 14 (2.6%) and 16 (3.0%) with chronic HBV. In the pembro and pbo arms, 6.0% and 5.4% with clinically resolved and 100% and 93.8% with chronic HBV received antiviral drugs during the study. Among evaluable pts with clinically resolved HBV, 4 (3.1%) of 127 in the pembro arm and 1 (0.8%) of 128 in the pbo arm had HBV reactivation. Among evaluable pts with chronic HBV, 1 (11.1%) of 9 in the pembro arm and 2 (15.4%) of 13 in the pbo arm had HBV reactivation. All reactivation was detected by HBV DNA increase. No pts developed HBV-associated hepatitis.

Conclusions

The low incidence of HBV reactivation and lack of HBV-associated hepatitis in pts with clinically resolved or controlled chronic HBV on antiviral therapy suggest that with careful monitoring, pembro plus gem/cis is unlikely to affect underlying HBV in advanced BTC.

Clinical trial identification

NCT04003636, first posted July 1, 2019.

Editorial acknowledgement

Editorial assistance in the writing of this abstract was provided by Melanie A. Leiby, PhD, 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

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. R.S. Finn: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Institutional, Research Grant: Adaptimmune, Bayer, Bristol Myers Squibb, Eisai, Eli Lilly, Pfizer, Roche, Genentech; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Bayer, Bristol Myers Squibb, Exelixis, Cstone, Hengrui, Eisai, Eli Lilly, MSD, Pfizer, Roche, Genentech; Financial Interests, Personal, Other, honoraria: Genentech; Financial Interests, Personal, Advisory Board: AstraZeneca, Hengrui. J.W. Valle: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Advisory Role: Ipsen, Novartis, AstraZeneca, Merck & Co., Inc., Rahway, NJ USA, Pfizer, PCI Biotech, Incyte, Keocyt, QED Therapeutics, Pieris Pharmaceutical, Genoscience Pharma, Mundipharma, Wren Laboratories, Nucana, Debiopharm Group, Imaging Equipment Ltd, Hutchison MediPharma, Zymeworks, Aptitude Health, Sirtex Medica, Baxter, Medivir, Cantargia AB, Autem Medical, Taiho Oncology, Servier, Boehringer Ingelheim; Financial Interests, Personal, Speaker’s Bureau: Novartis, Ipsen, Nucana, Imaging Equipment Limited, Mylan, Incyte, Servier, Delcath systems; Financial Interests, Personal, Other, travel: Nucana, Lilly, Roche, AstraZeneca/MedImmune. 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, 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; Financial Interests, Institutional, Coordinating PI: Bayer, Exelixis, AstraZeneca, Merck; Financial Interests, Institutional, Research Grant: Partner Therapeutics; Non-Financial Interests, Advisory Role, IDMC chair and member: Genentech/Roche; Non-Financial Interests, Principal Investigator: Exelixis, AstraZeneca; Non-Financial Interests, Advisory Role, IDMC member: Merck. 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. J. Furuse: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Incyte Biosciences Japan, Eisai, MSD, Ono Pharmaceutical, Sanofi, JPharma, Daiichi Sankyo, Sumitomo Dainippon, Taiho Pharmaceutical, Takeda, DeltaFly Pharma, Chugai Pharma; Financial Interests, Personal, Other, honoraria: Ono Pharmaceutical, Incyte Biosciences Japan, Eisai, Eli Lilly Japan, Yakult Honsha, Servier Japan, Novartis Pharma, Takeda, Bayer, EA Pharma, Teijin Pharma, Daiichi Sankyo, Terumo; Financial Interests, Personal, Advisory Board, honoraria: Chugai Pharmaceutical, AstraZeneca, MSD, Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Onco Therapy Science, Astellas, Takara Bio, Merck Bio. Z. Ren: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Advisory Role: MSD, AstraZeneca, Roche; Financial Interests, Personal, Invited Speaker: Bayer, MSD, Roche. T. Yau: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, MSD, AstraZeneca, Eisai, Ipsen; Financial Interests, Personal, Other, travel: Roche, Bayer; Financial Interests, Personal, Stocks/Shares: Moderna; Financial Interests, Personal, Writing Engagement: Taiho, Ipsen; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, MSD, Exelixis, Eli Lilly, AstrZeneca, Roche, Taiho . H.J. Klumpen: Financial Interests, Institutional, Invited Speaker, current treatments of cholangiocarcinoma: Medtalk; Financial Interests, Institutional, Invited Speaker, Podcast on treatment of HCC: CCO; Financial Interests, Institutional, Advisory Board: Janssen, AstraZeneca; Financial Interests, Institutional, Local PI, IMBRAVE 050: Roche; Financial Interests, Institutional, Local PI, FIGHT 302: INCYTE; Financial Interests, Institutional, Local PI, LEAP 012: MSD; Financial Interests, Institutional, Local PI, TAS120: Taiho; Financial Interests, Institutional, Local PI, Compete, Compose: ITM Solucin GmbH; Financial Interests, Institutional, Local PI, Keynote 966: MSD; Financial Interests, Institutional, Local PI, COSMIC 312: Exelixis; Other, Subdomain leader G5.1: EURACAN; Other, In the Netherlands: Member National Guideline committee for biliary tract cancer; Other, in the Netherlands: Member of the National guideline committee for HCC. M. Ozaka: Financial Interests, Institutional, Funding: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Other, honoraria: Taiho Pharmaceutical, Yakult Honsha, MSD, Ono Pharmaceuticals, Nihon, Servier, Bayer, Pfizer. C. Verslype: Financial Interests, Personal, Advisory Board: Roche, Bayer; Financial Interests, Personal, Invited Speaker: Ipsen, Bayer; Financial Interests, Institutional, Research Grant, unrestricted: Bayer; Non-Financial Interests, Member, Lobby group: Pancreatic Cancer Europe. 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, 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; 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, Principal Investigator: Unicancer. M. Ueno: Financial Interests, Personal, Invited Speaker: AstraZeneca, Chugai Pharmaceutical, Incyte, MSD, Nihon Servier, Ono Pharmaceutical, Taiho Pharmaceutical; Financial Interests, Personal, Advisory Board: Nippon Boehringer Ingelheim; Financial Interests, Institutional, Local PI: Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DFP, Daiichi Sankyo, Eisai, Incyte, MSD, Merck Biopharma, Ono Pharmaceutical, Taiho Pharmaceutical, Novartis. A. Vogel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Böhringer Mannheim, Eisai, Incyte, Ipsen, Janssen, MSD, PierreFabre, Roche, Servier, Sirtex, Tyra, Tahio; Financial Interests, Personal, Invited Speaker: BMS, Eisai, Incyte, Ipsen, Lilly, MSD, Roche; Financial Interests, Personal, Steering Committee Member: Roche, MSD, BeiGene, Jiangsu Hengrui Medicines. L. Yu: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. U. Malhotra: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. A.B. Siegel: Financial Interests, Personal, Full or part-time Employment: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc., Rahway, NJ, USA. S. Qin: Financial Interests, Institutional, Research Funding: MSD; Financial Interests, Personal and Institutional, Principal Investigator: Cina.