Phase Ib/II trial of talimogene laherparepvec alone and with pembrolizumab in advanced solid tumors with liver metastases and hepatocellular carcinoma

Abstract

Hepatocellular carcinoma; Liver metastasis; Solid tumor

Carcinoma hepatocelular; Metástasis hepática; Tumor sólido

Carcinoma hepatocel·lular; Metàstasi hepàtica; Tumor sòlid

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.

Medical writing support was provided by Shubha Dastidar, PhD, CMPP (Cactus Life Sciences, part of Cactus Communications) and was funded by Amgen Inc. The study was sponsored and funded by Amgen Inc. This study is in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. This study was sponsored by Amgen Inc.