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

Abstract

Abstract Background In HCC, surgical resection is associated with high recurrence rates, and no effective neoadjuvant or adjuvant therapies currently exist. Immunotherapy using anti-PD-1 antibodies has shown promised but limited increase in survival in advanced disease. To maximize the benefit, we are studying the efficacy and safety of anti–PD-1 (nivolumab) and anti–CTLA-4 (ipilimumab) antibodies against HCC for resectable HCC. Methods This is a randomized phase II trial of nivolumab (Arm A) or nivolumab + ipilimumab (Arm B) as pre-operative treatment for patients (pts) with HCC who are eligible for surgical resection. Pts are given nivolumab 240 mg every 2 weeks (wks) for a total of 6 wks. Pt in Arm B are treated concurrently with ipilimumab 1 mg/kg every 6 wks. Surgical resection occurs within 4 wks after last cycle of therapy. Pts continue adjuvant immunotherapy for up to 2 years after resection. The primary objective is the safety/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 Twenty-six patients were enrolled at the time of this interim analysis, of which 20 have evaluable data.Most pts (55%) were between 60-70yo and male (75%).Seven pts were HCV-positive, 7 had HBV and 6 had no hepatitis. 20 patients proceeded with resection as planned but surgery was aborted for 3 patients (1 for frozen abdomen and 2 development of contralateral liver nodule). Three are still receiving preoperative therapy. Pathologic complete response (pCR) was observed in 5/20 evaluable patients – 2 in Arm A and 3 Arm B (25% pCR rate). Five patients in Arm B and 1 in Arm A experienced grade 3 or higher toxicity prior to surgery. No grade 4 or higher toxicity were observed. Conclusions We report a pCR rate of 25% for resectable HCC after preoperative immunotherapy in a randomized phase II pilot trial. Treatment was safe and surgical resection was not delayed. The study is ongoing. These promising results may contribute to a paradigm shift in the perioperative treatment of resectable HCC. Legal entity responsible for the study BMS Pharmaceuticals. Funding BMS Pharmaceuticals. Disclosure All authors have declared no conflicts of interest.