Phase 1/2 study of durvalumab and tremelimumab as monotherapy and in combination in patients with unresectable hepatocellular carcinoma (HCC).

TPS3103 Background: No approved standard-of-care treatment options exist for patients with unresectable HCC who progress on, are intolerant to, or have refused sorafenib therapy. The PD-1/PD-L1 pathway is an important immune checkpoint used by tumor cells to block antitumor responses. Durvalumab is a selective, high-affinity human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 (IC50 0.1 nM) and CD80 (B7.1; IC50 0.04 nM). Tremelimumab is an IgG2 monoclonal antibody that inhibits CTLA-4. Tremelimumab monotherapy can induce objective tumor remission with a favorable safety profile in patients with HCC.1Targeting both PD-L1 and CTLA-4 pathways provides nonredundant pathway blockade of critical immune checkpoints. Methods: This phase 1/2, multicenter, open-label, randomized study evaluates the safety, tolerability, and antitumor activity of durvalumab and tremelimumab each as monotherapy (20 and 10 mg/kg Q4W, respectively) and in combination (20 and 1 mg/kg Q4W, respectively) in patients with unresectable HCC with or without concomitant viral hepatitis B or hepatitis C infection who have progressed on, are intolerant to, or have refused treatment with sorafenib. Key exclusion criteria are prior exposure to immune-mediated therapy, hepatic encephalopathy, active or prior documented gastrointestinal variceal bleed, and any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer. The primary objective is to assess the safety and tolerability of durvalumab and tremelimumab each as monotherapy and in combination. Key secondary objectives are to evaluate clinical outcomes (including objective response rate, duration of response, and overall survival) and describe the pharmacokinetics, pharmacodynamics (including PD-L1 expression), and immunogenicity of durvalumab and tremelimumab as monotherapy and in combination. Recruitment is ongoing. 1. Sangro B, et al. J Hepatol. 2013;59:81-8. Clinical trial information: NCT02519348.