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Background & Aims: Patients with advanced hepatocellular carcinoma (aHCC) and Child-Pugh B liver function are often excluded from clinical trials. In previous studies, overall survival for these patients treated with sorafenib was ∼3-5 months; thus, new treatments are needed. Nivolumab, alone or in combination with ipilimumab, is conditionally approved in the United States to treat patients with aHCC who previously received sorafenib. We describe nivolumab monotherapy outcomes in patients with Child-Pugh B status., Methods: This phase I/II, open-label, non-comparative, multicentre trial (27 centres) included patients with Child-Pugh B (B7-B8) aHCC. Patients received intravenous nivolumab 240 mg every 2 weeks until unacceptable toxicity or disease progression. Primary endpoints were objective response rate (ORR) by investigator assessment (using Response Evaluation Criteria in Solid Tumors v1.1) and duration of response. Safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events v4.0., Results: Twenty-five sorafenib-naive and 24 sorafenib-treated patients began treatment between November 2016 and October 2017 (median follow-up, 16.3 months). Investigator-assessed ORR was 12% (95% CI 5-25%) with 6 patients responding; disease control rate was 55% (95% CI 40-69%). Median time to response was 2.7 months (interquartile range, 1.4-4.2), and median duration of response was 9.9 months (95% CI 9.7-9.9). Treatment-related adverse events (TRAEs) were reported in 25 patients (51%) and led to discontinuation in 2 patients (4%). The most frequent grade 3/4 TRAEs were hypertransaminasemia (n = 2), amylase increase (n = 2), and aspartate aminotransferase increase (n = 2). The safety of nivolumab was comparable to that in patients with Child-Pugh A aHCC., Conclusions: Nivolumab showed clinical activity and favourable safety with manageable toxicities, suggesting it could be suitable for patients with Child-Pugh B aHCC., Lay Summary: In patients with advanced hepatocellular carcinoma, almost all systemic therapies require very good liver function, i.e. Child-Pugh A status. The evidence from this study suggests that nivolumab shows clinical activity and an acceptable safety profile in patients with hepatocellular carcinoma with Child-Pugh B status who have mild to moderate impairment of liver function or liver decompensation that might rule out other therapies. Further studies are warranted to assess the safety and efficacy of nivolumab in this patient population., Clinical Trial Number: NCT01658878., Competing Interests: Conflict of interest MK reports receiving personal fees from Bristol Myers Squibb, Bayer, Eisai, MSD, and Ono Pharmaceutical Co., Ltd., and receiving grants from Eisai, Otsuka, Taiho Pharmaceutical, EA Pharma, Takeda, AbbVie, and Gilead Sciences. AM reports receiving personal fees from Bayer, BTG, and Bristol Myers Squibb and receiving grants and other funding from Bayer. AS reports receiving personal fees from Bristol Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Takeda, Roche, AbbVie, Amgen, Celgene, ArQule, Lilly, Sandoz, and Novartis. IM reports receiving personal fees from Alligator Bioscience, Bristol Myers Squibb, EMD Serono, F-Star Biotechnology, Genmab, Roche, Bayer, MSD, Numab, Lilly, AstraZeneca/MedImmune, Incyte, and Tusk Therapeutics and receiving grants from Pfizer, Alligator Bioscience, Bristol Myers Squibb, and Roche. SP reports receiving personal fees from Celgene, Novartis, Eisai, Bristol Myers Squibb, Shire, and Sirtex Medical; receiving grants from Bristol Myers Squibb; and receiving non-financial support from Bristol Myers Squibb, Amgen, and Merck. ABE reports receiving personal fees from CytomX Therapeutics, Bristol Myers Squibb, Bayer, Eisai, Roche/Genentech, EMD Serono, Exelixis, Pieris Pharmaceuticals, Agenus, and Merck and receiving grants from AstraZeneca, Merck, and Astex Pharmaceuticals. RK reports receiving research funding from Bristol Myers Squibb, Eisai, Ono Pharmaceutical Co., Ltd., MSD KK, AstraZeneca plc, EA Pharma Co., Ltd, Takeda Pharmaceutical Company Limited, CHUGAI Pharmaceutical Co, LTD and honoraria from MSD, Mitsubishi Tanabe Pharma Corporation, Shionogi & Co., Ltd, GE Healthcare Japan, Daiichi Sankyo Company, Limited. BE reports receiving personal fees from Bayer, Lexicon, RTI Health Solutions, BTG, Loxo, Merrimack, and Bristol Myers Squibb; receiving grants from AVEO, Boston Biomedical, Bristol Myers Squibb, Cleave Biosciences, Five Prime Therapeutics, Genentech, Hoosier Cancer Research Network, ICON Clinical Research, Merck, Novartis, Pfizer, PPD, Taiho Pharmaceutical, Xencor, and AstraZeneca/MedImmune; and receiving other funding from Exelixis and ERYTECH Pharma. YI reports receiving personal fees from Gilead Sciences Inc, AbbVie Inc, Merck Sharp & Dohme, Bristol Myers Squibb, Ono Pharmaceutical Co., Ltd., funding from Takeda Pharmaceutical Company Limited, EA Pharma Co, Ltd, Eisai Co Ltd, AbbVie Inc, Merck Sharp & Dohme, Bayer Yakuhin Ltd, Bristol Myers Squibb, Astellas Pharma Inc, Nissan Chemical Industries, Ltd, FUJIREBIO Inc, Ono Pharmaceutical Co., Ltd., Gilead Sciences Inc, and Nichinichi Pharmaceutical Co Ltd. MR reports receiving personal fees from Bayer, Bristol Myers Squibb, AstraZeneca, Ipsen, Lilly, BTG, and Roche; receiving grants from Bayer and Lilly; and receiving non-financial support from Bayer and Bristol Myers Squibb. YS reports receiving personal fees from Bristol Myers Squibb; and receiving other funding from Bristol Myers Squibb and Sanofi. JN reports receiving personal fees and other funding from Bristol Myers Squibb. JA reports receiving personal fees and other funding from Bristol Myers Squibb. TW reports receiving personal fees, grants, and other funding from Bristol Myers Squibb. BS has served in a consulting or advisory role for Adaptimmune, AstraZeneca, Bayer, Bristol Myers Squibb, BTG, Merck, Onxeo, Sirtex Medical, TERUMO, H3 Biomedicine, Ipsen, Lilly, and Roche; has served on speakers’ bureaus for Bayer, Bristol Myers Squibb, Sirtex Medical, TERUMO, and Ipsen; and has received research funding from Bristol Myers Squibb and Sirtex Medical. ACG, MA, KN, FD, and OC report no disclosures. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Nivolumab, an immune checkpoint inhibitor, is approved in several countries to treat sorafenib-experienced patients with HCC, based on results from the CheckMate 040 study (NCT01658878). Marked differences exist in HCC clinical presentation, aetiology, treatment patterns and outcomes across regions. This analysis assessed the safety and efficacy of nivolumab in the Asian cohort of CheckMate 040., Methods: CheckMate 040 is an international, multicentre, open-label, phase I/II study of nivolumab in adults with advanced HCC, regardless of aetiology, not amenable to curative resection or local treatment and with/without previous sorafenib treatment. This analysis included all sorafenib-experienced patients in the intent-to-treat (ITT) overall population and Asian cohort. The analysis cut-off date was March 2018., Results: There were 182 and 85 patients in the ITT population and Asian cohort, respectively. In both populations, most patients were older than 60 years, had BCLC (Barcelona Clinic Liver Cancer) Stage C disease, and had received previous systemic therapy. A higher percentage of Asian patients had HBV infections, extrahepatic metastases and prior therapies. Median follow-up was 31.6 and 31.3 months for the ITT and Asian patients, respectively. Objective response rates were 14% and 15% in the ITT population and Asian cohort, respectively. In the Asian cohort, patients with HBV, HCV or those who were uninfected had objective response rates of 13%, 14% and 21%, respectively. The median duration of response was longer in the ITT (19.4 months) vs. Asian patients (9.7 months). Median overall survival was similar between the ITT (15.1 months) and Asian patients (14.9 months), and unaffected by aetiology in Asian patients. The nivolumab safety profile was similar and manageable across both populations., Conclusion: Nivolumab safety and efficacy are comparable between sorafenib-experienced ITT and Asian patients., Lay Summary: The CheckMate 040 study evaluated the safety and efficacy of nivolumab in patients with advanced hepatocellular carcinoma who were refractory to previous sorafenib treatment or chemotherapy. This subanalysis of the data showed that treatment responses and safety in patients in Asia were similar to those of the overall treatment population, providing support for nivolumab as a treatment option for these patients. Clinical trial number: NCT01658878., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)