A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEM) in patients (pts) with unresectable hepatocellular carcinoma (uHCC).

4076 Background: LEN is a multikinase inhibitor of VEGFR 1–3, FGFR 1–4, PDGFRα, RET, and KIT that showed noninferiority with respect to overall survival (OS) compared with sorafenib in the first-line treatment of pts with uHCC in a phase (Ph) 3 trial (REFLECT). PEM is an anti-PD-1 monoclonal antibody that has shown promising activity in HCC. An ongoing Ph 1b study of LEN + PEM has shown promising activity in several solid tumor types. We report preliminary results from a Ph1b trial of LEN + PEM in pts with uHCC. Methods: In this open-label, multicenter study, pts with uHCC, BCLC stage B (not eligible for transarterial chemoembolization) or C, Child-Pugh class A, and ECOG PS ≤ 1 received LEN (body weight ≥ 60 kg: 12 mg/day; < 60 kg: 8 mg/day) daily and 200 mg PEM IV once every 3 wks. Tolerability was evaluated by assessing dose-limiting toxicities (DLTs) during the first cycle in pts who were ineligible for other therapies (3+3 design; Part 1). Once tolerability of the combination was confirmed, additional pts with no prior systemic therapy for uHCC were enrolled (Part 2). The primary endpoint was safety. Secondary and exploratory endpoints included OS, and objective response rate, progression-free survival, and time to progression using modified RECIST (mRECIST). Tumor assessments of complete or partial responses (CR or PR) were confirmed ≥ 4 weeks after initial response. Results: As of December 1, 2017, 18 pts had received LEN + PEM (Part 1: n = 6; Part 2: n = 12). Pts had BCLC stage B (n = 6) or C (n = 12), Child-Pugh scores of 5 (n = 14) or 6 (n = 4), and 4 pts (22%) had received prior sorafenib. No DLTs were reported in Part 1. All 18 pts remained on study. TEAEs occurred in 17 pts (94%); the most common TEAEs were decreased appetite and hypertension (56% each). No new safety signals were identified. Efficacy outcomes are reported in the Table. At data cutoff, tumor reduction from baseline was observed in all evaluable pts except one. Conclusions: LEN + PEM was well tolerated with encouraging anti-tumor activity in pts with uHCC. Clinical trial information: NCT03006926. Part 1 (n = 6) Part 2 (n = 7) Total (n = 13) Best Overall Response, n (%) PR* 4 (67) 2 (29) 6 (46) Stable Disease 2 (33) 4 (57) 6 (46) Progressive Disease 0 (0) 0 (0) 0 (0) Not Evaluable 0 (0) 1 (14) 1 (8) *3 PRs confirmed.