615O - Safety and preliminary efficacy of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (aHCC): Interim analysis of the phase...

Date 09 October 2016
Event ESMO 2016 Congress
Session Gastrointestinal tumours, non-colorectal 2
Topics Hepatobiliary Cancers
Presenter Ignacio Melero
Citation Annals of Oncology (2016) 27 (6): 207-242. 10.1093/annonc/mdw371
Authors I. Melero1, B. Sangro2, T. Yau3, C. Hsu4, M. Kudo5, T. Crocenzi6, T. Kim7, S. Choo8, J. Trojan9, T. Meyer10, T.H. Welling III11, W. Yeo12, A. Chopra13, J. Anderson14, C. Dela Cruz15, L. Lang16, J. Neely17, A. El-Khoueiry18
  • 1Laboratory Of Immunology, Universidad de Navarra, 31009 - Pamplona/ES
  • 2Laboratory Of Immunology, Universidad de Navarra and CIBERehd, 31009 - Pamplona/ES
  • 3Medicine, Queen Mary Hospital University of Hong Kong, Hong Kong/CN
  • 4Graduate Institute Of Oncology, National Taiwan University NTU, College of Medicine, 100 - Taipei/TW
  • 5Hepatology, Gastroenterology, Kinki University, Osaka/JP
  • 6Medical Oncology, Providence Portland Medical Center, 97213 - Portland/US
  • 7Department Of Internal Medicine, Seoul National University, Seoul/KP
  • 8Medical Oncology, National Cancer Center, Singapore/SG
  • 9Medizinische Klinik, Universitätsklinikum Frankfurt(Johannes-Wolfgang Goethe Institute), Frankfurt am Main/DE
  • 10Department Of Oncology, Royal Free London NHS Foundation Trust, NW3 2QG - London/GB
  • 11General Surgery, University of Michigan, Ann Arbor/US
  • 12Department Of Clinical Oncology, The University of Hong Kong, Hong Kong/CN
  • 13Hematology And Oncology, Johns Hopkins Singapore International Medical Center, Singapore/SG
  • 14Oncology, Bristol-Myers Squibb, 08540 - Princeton/US
  • 15Global Clinical Research, Bristol-Myers Squibb Company, 449269 - Singapore/SG
  • 16Immuno-oncology, Bristol-Myers Squibb, 08540 - Princeton/US
  • 17Oncology Biomarkers, Bristol-Myers Squibb, 08540 - Princeton/US
  • 18Clinical Medicine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles/US

Abstract

Background

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

Methods

Pts had histologically confirmed aHCC, Child-Pugh (CP) scores ≤7 (ESC) or ≤6 (EXP). ESC pts previously failed, refused, or who were intolerant (intol) of sor received nivo 0.1–10 mg/kg for up to 2 yrs in 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, DOR, and PD-L1 assessment.

Results

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 77% and 68% 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% 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 AST (4%) increase, lipase and ALT (3% each) increase, and amylase (2%) increase. Efficacy data are presented in Table 1. Responses occurred regardless of underlying HCC etiology and PD-L1 expression.

Efficacy

ESC (n = 48) EXP (n = 214)
ORR, n (%) (95% CI) 7 (15) (6, 28) 35 (16) (12, 22)
CR, n (%) 3 (6) 2 (1)
PR, n (%) 4 (8) 33 (15)
SD, n (%) 24 (50) 111 (52)
PD, n (%) 15 (31) 63 (29)
Not evaluable 2 (4) 5 (2)
Median DOR, mo (95% CI) 17 (6, 24) Not estimable
Median OS (95% CI) 14.3 (9.6, 18.9) a
OS rate (all) OS Rate, % (95% CI) 6 mo 9 mo 12 mo Sor naïve/intol OS Rate, % (95% CI) 6 mo 9 mo 12 mo Sor treated OS Rate, % (95% CI) 6 mo 9 mo 12 mo 66.0 (50.6, 77.6) 66.0 (50.6, 77.6) 59.1 (43.6, 71.7) n = 11 63.6 (29.7, 84.5) 63.6 (29.7, 84.5) 63.6 (29.7, 84.5) n = 37 66.7 (48.9, 79.5) 66.7 (48.9, 79.5) 57.6 (39.7, 71.9) 82.5 (75.8, 87.5) 70.8 (56.6, 81.1) Not calculatedb n = 69 88.1 (76.5, 94.2) 72.3 (44.7, 87.7) Not calculated n = 145 80.2 (71.7, 86.5) 71.8 (56.2, 82.6) Not calculated

aData not mature; bNot calculated when N at risk is

Conclusions

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.

Legal entity responsible for the study

Sponsored by Bristol-Myers Squibb

Funding

Sponsored by Bristol-Myers Squibb

Disclosure

I. Melero: Advisory Board consulting for BMS, Roche-Genentech, Astrazeneca-medimmune, Boehringer Ingelheim, Alligaror, Incyte. B. Sangro: Personal fees from Bristol-Myers Squibb, Astra Zeneca, Bayer Healthcare, outside the submitted work. M. Kudo: Honoraria: Bayer, Eisai, Ajimomoto, Kaken Pharma. Research funding: Taicho, Bayer, BMS, Kowa, Chugai, Lilly, Novartis, Pfizer. Consultant or Advisory: Taicho, Bayer, BMS, Kowa, Chugai. T. Crocenzi: Clinical research support and meeting/travel reimbursement for advisory board meeting: BMS, outside the submitted work. S.-P. Choo: Honorarium: Bristol-Myers Squibb. J. Trojan: Advisory boards and speakers bureau member: BMS. W. Yeo: Grants: Bristol-Myers Squibb during the conduct of the study. A. Chopra: Honoraria for participation in advisory board: MSD Oncology, Lilly. Travel grants: BMS, BI, Bayer, Merck, Serono. J. Anderson: Employee at BMS. A. El-Khoueiry: Honoraria and travel expenses: BMS, Bayer, AstraZeneca, Genetech, GSK. Consultant: BMS, AstraZeneca, Genetech/Roche. Research funding: Astex. Speakers' Bureau: Merimak.

All other authors have declared no conflicts of interest.