CA209-9DX: phase III, randomized, double-blind study of adjuvant nivolumab vs placebo for patients with hepatocellular carcinoma (HCC) at high risk of recurrence after curative resection or ablation

Abstract

Background: Despite significant improvements in the treatment of early HCC, curative therapies remain associated with high recurrence rates (≥ 70% at 5 y) (EASL. J Hepatol 2018), and therefore, adjuvant therapies are needed. Nivolumab (NIVO) has demonstrated durable tumor responses and a manageable safety profile in patients (pts) with advanced HCC, regardless of HCC etiology (CheckMate‐040 study) (El‐Khoueiry, et al. Lancet 2017). Additionally, NIVO has shown clinical benefit as adjuvant therapy in melanoma (CheckMate‐238 study) (Weber, et al. NEJM 2017). This phase 3, randomized, double‐blind, placebo‐controlled study will evaluate the safety and efficacy of adjuvant NIVO in pts with HCC who are at high risk of recurrence after curative hepatic resection or ablation, a population for whom no effective therapies are currently available. Trial design: The trial will include 530 pts aged ≥ 18 y with a first diagnosis of HCC (any etiology) who are at high risk for HCC recurrence after curative resection or ablation, and who have well‐preserved liver function (Child‐Pugh score 5 or 6), randomized (1:1) to receive NIVO (480 mg intravenous Q4W) or placebo (PBO). Additional eligibility criteria include Eastern Cooperative Oncology Group performance status of 0 or 1, no evidence of tumor metastasis, no prior therapy for HCC (including locoregional therapies), and no liver transplant. Pts will be treated until recurrence per blinded independent central review (BICR) assessment, unacceptable toxicity, or withdrawal, or for up to 1 y total duration. Survival follow‐up will continue for up to 5 y. The primary endpoint is to compare recurrence‐free survival, per BICR assessment. Secondary endpoints include overall survival and time to recurrence (defined as time from randomization to first documented disease recurrence). The trial will be open for enrollment in 20 countries worldwide and is currently recruiting.