Safety and antitumor activity of nivolumab (nivo) in patients (pts) with advanced hepatocellular carcinoma (HCC): Interim analysis of dose-expansion cohorts from the phase 1/2 CheckMate-040 study.

4078 Background: HCC tumors are associated with chronic inflammation that can promote an immunosuppressive environment; anti-PD-1 therapy may counter this inhibition. Nivo, a fully human IgG4 monoclonal antibody PD-1 inhibitor, was initially evaluated in a multiple ascending-dose, phase 1/2 study in pts with advanced HCC; it was well tolerated with antitumor activity in different etiologies, across lines of therapy, justifying an expansion phase. Interim results are presented. Methods: Pts had histologically confirmed, advanced HCC and Child-Pugh class A. Dose expansion at nivo 3 mg/kg occurred in 4 cohorts: uninfected sorafenib (sor) naïve/intolerant, uninfected sor progressors, HCV-, and HBV-infected. Primary endpoint was confirmed overall response rate (ORR) by RECIST 1.1. Secondary endpoints included OS, PFS, time to progression, and biomarker assessment. Results: Dose expansion enrolled 206 pts; 75% had extrahepatic metastasis, 7% vascular invasion, and 64% prior sor. Across cohorts, pts received a median of 5–6 doses (range: 1–19). Treatment-related AEs (TRAEs) occurred in 104 pts (50%); the most frequent were fatigue (17%) and pruritus (12%). Grade 3/4 TRAEs were seen in 28 pts (14%); most common were ALT and AST increases (3% each). 68 of 174 evaluable pts (39%) had a decline in tumor burden. Preliminarily, 91 pts (55%) had ≥ 18 wks follow-up and/or PD. ORR for these pts was 9% (8/91) [14% (3/22) uninfected sor naïve/intolerant; 7% (2/27) uninfected sor progressors; 14% (3/21) HCV-infected; (0/21) HBV-infected]. 6 mos OS rate was 69% (95% CI, 0.43–0.85). Responses were observed in pts with and without quantifiable PD-L1 measured by IHC. Antiviral responses in HCV- and HBV-infected pts have been observed as measured by declines in HCV RNA and quantitative HBV surface antigen. Conclusions: AEs were consistent across nivo cohorts and similar to profiles in other tumor types. Results are preliminary and may underestimate response; data indicate activity across all etiologic subtypes and lines of therapy, supporting ongoing study of nivo in HCC. Clinical trial information: NCT01658878.