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.
