Background

Many patients (pts) with advanced HCC progress on sorafenib therapy, and limited treatment options are available. Nivolumab, a fully human IgG4 mAb inhibitor of PD-1, demonstrated durable responses (objective response rate [ORR], 20%; median duration of response [DOR], 9.9 mo; 9-mo overall survival [OS] rate, 74%) in pts with advanced HCC in the dose-expansion (EXP) phase of the CheckMate 040 study (El-Khoueiry, Sangro, et al. 2017). Here we present survival, durability of response, and safety data in Asian pts with advanced HCC in the CheckMate 040 study.

Methods

Pts naive to or previously treated with sorafenib received nivolumab in phase 1/2 dose-escalation (ESC; 0.1–10 mg/kg) and -EXP (3 mg/kg) cohorts every 2 weeks regardless of PD-L1 status. Primary endpoints were safety and tolerability (ESC) and ORR (EXP; reported by blinded independent central review) using RECIST v1.1. Secondary endpoints included DOR, disease control rate (DCR), and OS.

Results

Asian pts (N = 107) from Hong Kong (n = 25), Japan (n = 32), Korea (n = 13), Singapore (n = 15), and Taiwan (n = 22) were included in the analysis; median follow-up was 19.2 mo. Median age was 62 yr, and 99% had Child-Pugh scores of 5–6. Overall, 18% and 50% of pts were HCV or HBV infected, respectively; 32% were uninfected. In sorafenib-naive pts (n = 22), the ORR was 14% (Table), and the DCR was 41%. In sorafenib-experienced pts (n = 85), the ORR was 15%, and the DCR was 49%. Across the cohorts, the median DOR was 13.8 mo; 6 of 16 responses (38%) were ongoing. Treatment-related AEs (TRAEs; any grade) and grade 3/4 TRAEs occurred in 75% and 11% of pts, respectively; rates of grade 3/4 ALT and AST elevations were 1%–2%. Additional baseline, efficacy, and safety data, stratified by patient age (<65 and ≥65 yr), will be presented.Table: 195O

Nivolumab Efficacy in Asian Patients

Conclusions

Nivolumab demonstrated durable responses and manageable safety in Asian pts with advanced HCC with or without chronic viral hepatitis.

Clinical trial identification

NCT01658878

Legal entity responsible for the study

Bristol-Myers Squibb

Funding

Bristol-Myers Squibb

Disclosure

S.P. Choo: Advisory boards for Sirtex, Shire, BMS, Norvatis, Celgene; and received travel funding from Amgen and Merck. Y-K. Kang: Consulting/advisory role for Lilly/ImClone, Novartis, ONO Pharmaceutical, Roche/Genentech and Taiho Pharmaceutical; research funding from Bayer, Novartis and Roche/Genentech. W. Yeo: Honoraria from Bristol-Myers Squibb, Novartis and Pfizer; consulting/advisory role for Novartis and Pfizer; speakers\' bureau for Lilly. A. Chopra: Travel grant from BMS to travel to ASCO 2016 and 2017. Has also received fees for giving a talk at BASCO, Thailand in 2016 from BMS. Has also attended advisory board on invitation from BMS in 2016. A. Baakili, C. Dela Cruz, H. Zhao: Employment with Bristol-Myers Squibb. M. Kudo: Lectures for Bayer, Eisai, MSD, Ajinomoto, Kowa, Taiho; grants from Chugai, Otsuka, Takeda, Taiho, Sumitomo Dainippon, Daiichi, Sankyo, MSD, Eisai, Bayer, Abbvie, Medico’s Hirata, Astellas Pharma, Bristol-Myers Squibb, Eli Lilly, Pfizer, Novartis, Kaken and advisory consulting for Kowa, MSD, BMS, Bayer, Chugai, Taiho, Eisai, Ono. All other authors have declared no conflicts of interest.