219O - Safety and preliminary efficacy of nivolumab in patients with advanced hepatocellular carcinoma: interim analysis of the phase 1/2 CheckMate-040 study

Date 19 December 2016
Event ESMO Asia 2016 Congress
Session Gastrointestinal tumours
Topics Hepatobiliary Cancers
Presenter Ignacio Melero
Citation Annals of Oncology (2016) 27 (suppl_9): ix68-ix85. 10.1093/annonc/mdw582
Authors I. Melero1, B. Sangro1, T. Yau2, C. Hsu3, M. Kudo4, T. Crocenzi5, T. Kim6, S.P. Choo7, J. Trojan8, T. Meyer9, T.H. Welling III10, W. Yeo2, A. Chopra11, J. Anderson12, C. Dela Cruz12, L. Lang12, J. Neely12, A. El-Khoueiry13
  • 1Department Of Medical Oncology, Clinica Universidad de Navarra and CIBERehd, 31008 - Pamplona/ES
  • 2Department Of Medicine, The University of Hong Kong, NA - Hong Kong/CN
  • 3Department Of Oncology, National Taiwan University Hospital and National Taiwan University Cancer Center, 100 - Taipei/TW
  • 4Oncology, Kinki University School of Medicine, 3-4-1 - Osaka/JP
  • 5Department Of Medical Oncology, Providence Cancer Center, 97213 - Portland/US
  • 6Internal Medicine, Seoul National University Hospital (SNUH)-Yongon Campus, 110-744 - Seoul/KR
  • 7Medical Oncology, National Cancer Center, 169610 - Singapore/SG
  • 8Internal Medicine, Universitätsklinikum Frankfurt(Johannes-Wolfgang Goethe Institute), 60590 - Frankfurt am Main/DE
  • 9Medical Oncology, Royal Free Hospital, WC1E 6DD - London/GB
  • 10Surgery, Section Of Transplant Surgery, University of Michigan, 48109 - Ann Arbor/US
  • 11Medical Oncology, Johns Hopkins Singapore International Medical Center, 308 433 - Singapore/SG
  • 12Oncology, Bristol-Myers Squibb, 08540 - Princeton/US
  • 13Clinical Medicine, University of Southern California Norris Comprehensive Cancer Center, 90033 - Los Angeles/US



Median overall survival (OS) for first-line (1L) treatment of advanced hepatocellular carcinoma (aHCC) with sorafenib (sor) is up to 11 mo and 7–8 mo with best supportive care (BSC) post-sor failure. Nivolumab (nivo), an IgG4 mAb to the programmed death-1 (PD-1) receptor, was evaluated in a phase 1/2 study of patients (pts) with aHCC. After the multiple ascending-dose escalation (ESC) phase, dose expansion (EXP) followed. Interim results are presented.


Pts had histologically confirmed aHCC, Child-Pugh (CP) scores ≤ 7 (ESC) or ≤ 6 (EXP). ESC pts who previously failed, refused, or were intolerant (intol) of sor received nivo 0.1–10 mg/kg across 3 cohorts: uninfected HCC, HBV-, and HCV-infected. EXP pts received nivo 3 mg/kg across 4 cohorts: uninfected sor naïve/intol, uninfected sor progressors, HBV-, and HCV-infected. Primary endpoints were safety (ESC) and overall response rate (ORR) by RECIST 1.1 (EXP). Other endpoints included OS, duration of response (DOR), and programmed death-ligand 1 (PD-L1) assessment.


48 (ESC) and 214 (EXP) pts were enrolled and treated with nivo. At baseline, 85% and 70% were CP = 5, 77% and 75% had extrahepatic metastasis, and 73% and 66% had prior sor, for ESC and EXP, respectively. EXP safety profile was similar to that of previously reported ESC. In EXP, treatment-related adverse events (TRAEs) occurred in 65% of pts; 18% of pts had grade 3–4. Most common TRAEs were fatigue (21%), pruritus (15%), rash (12%), and diarrhea (9%); most common grade 3–4 TRAEs were increases in AST (4%), lipase and ALT (3% each), and amylase (2%). Efficacy data are presented in the table. Responses occurred regardless of underlying HCC etiology and PD-L1 expression.


Nivo was well tolerated in pts with aHCC. ORR and OS rate for ESC is favorable to historic BSC data. Tolerability and efficacy profiles are consistent between ESC and EXP phases of this ongoing study.

Clinical trial indentification

Protocol Number: CA209040 Release Date: May 25, 2012

Legal entity responsible for the study

Bristol-Myers Squibb


Bristol-Myers Squibb


I. Melero: Advisory board consulting for BMS, Roche-Genentech, Astrazeneca-medimmune, Boehringer Ingelheim, Alligator, Incyte. B. Sangro: Consulting or Advisory Role - Bayer; Bristol-Myers Squibb; MedImmune Speakers\' Bureau - Bayer; Bristol-Myers Squibb. M. Kudo: Honoraria: Bayer, Eisai, Ajinomoto, Kaken Pharma Consulting/Advisory Role: Taiho, Bayer, BMS, Kowa, Chugai Research Funding: Taiho, Bayer, BMS, Kowa, Chugai, Lilly, Novartis, Pfizer. T. Crocenzi: Consulting or Advisory Role - Bristol-Myers Squibb Research Funding - Bristol-Myers Squibb (Inst) Travel, Accommodations, Expenses - Bristol-Myers Squibb. S.P. Choo: advised for and received honorarium from BMS. J. Trojan: BMS:Aadvisory boards and speakers bureau member. W. Yeo: Grants: BMS. A. Chopra: Honoraria: Bayer; Janssen Consulting/Advisory: Astellas Pharma; Bayer; Boehringer Ingelheim; BMS; Lilly; MSD Oncology Research Funding: Eisai Travel/Accommodations, Expenses: Bayer; Boehringer Ingelheim; Merck Serono. J. Anderson, C. Dela Cruz, L. Lang, J. Neely: BMS employee and stockholder. A. El-Khoueiry: Honoraria/Travel Expenses: AstraZeneca, Bayer, BMS, Genentech, GSK Consulting: AstraZeneca, BMS, Genentech/Roche Speakers\' Bureau: Merrimack Research Funding: Astex Pharmaceuticals. All other authors have declared no conflicts of interest.