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

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.