A phase Ib study of lenvatinib (LEN) plus nivolumab (NIV) in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Study 117.

513 Background: LEN, a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT with immunomodulatory activity, is approved in multiple countries for first-line treatment of uHCC. NIV is an anti-PD-1 monoclonal antibody approved in multiple countries as a second-line treatment for HCC. We report early results from a phase 1b trial of LEN + NIV in pts with uHCC. Methods: In this open-label study, pts with uHCC, BCLC stage B (not eligible for transarterial chemoembolization) or C, Child-Pugh class A, and ECOG PS ≤ 1 received LEN (bodyweight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) PO QD and 240 mg NIV IV Q2W. The primary endpoint was tolerability and safety of the combination. Objective response rate (ORR; mRECIST by investigator) was a secondary endpoint. Tolerability was evaluated by assessing dose-limiting toxicities (DLTs) during the first cycle in pts for whom no other appropriate therapy was available (Part 1). Once tolerability was confirmed, additional pts with no prior systemic therapy for uHCC were enrolled (Part 2). Results: At data cutoff (May 17, 2019), 30 pts had received LEN + NIV (Part 1: n=6; Part 2: n=24). Pts had BCLC stage B (n=17) or C (n=13) and Child-Pugh scores of 5 (n=23) or 6 (n=7). 4 pts in Part 1 (66.7%) had received prior anticancer medications (3 pts had 1; 1 pt had ≥3). No DLTs were reported in Part 1. TEAEs leading to discontinuation of LEN were reported in 2 (6.7%) pts; 4 (13.3%) pts had TEAEs leading to discontinuation of NIV. TEAEs occurred in all 30 pts; the most common were palmar-plantar erythrodysesthesia (56.7%) and dysphonia (53.3%). Adverse events were manageable. Efficacy outcomes are reported (Table). Conclusions: LEN + NIV was well tolerated with encouraging anti-tumor activity in pts with uHCC. Clinical trial information: NCT03418922. [Table: see text]