Randomized, open-label, perioperative phase II study evaluating nivolumab alone versus nivolumab plus ipilimumab in patients with resectable HCC.

Abstract

185 Background: In HCC, surgical resection is associated with high recurrence rate, and no effective neoadjuvant or adjuvant therapies currently exist. On the basis of previous reports on the efficacy and safety of anti–PD-1 and anti–CTLA-4 antibodies against HCC, we initiated a randomized pilot trial of perioperative immunotherapy for resectable HCC. Methods: This is a randomized, phase II trial of nivolumab (Arm A) or nivolumab + ipilimumab (Arm B) as peri-operative treatment for patients (pt) with HCC who are eligible for surgical resection. Pt are given nivolumab 240 mg every 2 weeks (wk) for a total of 6 wk. Pt in Arm B are treated concurrently with ipilimumab 1 mg/kg every 6 wk. Surgical resection occurs within 4 wkafter last cycle of therapy. Pt continue adjuvant immunotherapy for up to 2 years after resection. Primary objective is the safety and tolerability of nivolumab +/- ipilimumab. Secondary objectives include overall response rate, complete response rate and time to progression. Exploratory objectives include evaluating the pre- and post-treatment immunological changes in tumor tissues and peripheral blood. Results: 9 pt were enrolled at the time of first interim analysis, and 8 pt were evaluable (5 in Arm A, 3 in Arm B). Pt were 60-69 yo, and males (78%). 5 pt were HCV-positive and 1 had chronic hepatitis B infection. 8 pt proceeded with resection as planned; surgery was aborted for 1 pt due to frozen abdomen from previous surgery. Pathologic complete response (pCR) was observed in 3/8 pt – 2 in Arm A and 1 Arm B (37.5% pCR). 2 pt in Arm B and 1 in Arm A experienced grade 3 or higher toxicity which did not affect their resectability. No grade 4 or higher toxicity were observed. Immune analysis of the first case with a pCR in Arm B demonstrated that clinical response correlated with an increase in CD8+ T cell infiltration, notably an increase in two effector T cell clusters. Conclusions: We report a pCR rate of 37.5% in the first interim analysis of a phase II pilot trial of perioperative immunotherapy for resectable HCC. Treatment was deemed safe and surgical resection was not delayed. The study is ongoing and results may contribute to a paradigm shift in the perioperative treatment of HCC. Clinical trial information: NCT03222076.