Phase Ib/II trial of talimogene laherparepvec alone and with pembrolizumab in advanced solid tumors with liver metastases and hepatocellular carcinoma
J. Randolph Hecht, A. Oberoi, Elena Garralda, Hong Jae Chon, Antonia Digklia, Sylvie Rottey, M. Martín Jiménez, Marya Chaney, Jane Hippenmeyer, Tatiana Lawrence, Kate Liu, Ali Hamidi, Jason Chesney
Abstract
BACKGROUND: Newer effective therapies are needed for patients with solid tumors with liver metastases and unresectable hepatocellular carcinoma (HCC). METHODS: Part 1 (dose exploration) evaluated intrahepatic talimogene laherparepvec (T-VEC) injection in group A (non-HCC liver metastases) and group B (HCC). Cohorts 1-4 received T-VEC monotherapy; cohorts 5 and 6 received T-VEC+pembrolizumab. Part 2 (dose expansion) evaluated intrahepatic or intratumoral T-VEC+pembrolizumab in non-HCC solid tumors. The primary endpoints were dose-limiting toxicities (DLTs) in part 1; objective response rate (ORR) per modified irRC-RECIST and safety in part 2. RESULTS: Part 1 enrolled 28 and 46 patients to receive T-VEC and T-VEC+pembrolizumab, respectively. Three patients reported DLTs (T-VEC, n = 2 grade 3 abdominal pain and aspartate transaminase increase; T-VEC+pembrolizumab, n = 1 grade 3 cholestatic hepatitis). ORR (secondary endpoint) with T-VEC was 0%; ORR (95% CI) with T-VEC+pembrolizumab was 8.3% (1.0, 27.0) for non-HCC and 13.6% (2.9, 34.9) for HCC. Part 2 enrolled 53 patients; ORR (95% CI) was 0% (0.0, 30.8)-20.0% (0.5, 71.6) across 5 tumor types, with 16.7% (95% CI: 3.6, 41.4) for triple-negative breast cancer with the largest sample size (n = 18). Safety findings were consistent with the therapies administered. CONCLUSIONS: Limited efficacy across tumor types evaluated limit further evaluation of intrahepatic T-VEC+pembrolizumab in this patient population. CLINICALTRIALS.GOV IDENTIFIER: NCT02509507.