A Phase II Randomized Trial of Talimogene Laherparepvec Oncolytic Immunotherapy with or Without Radiotherapy for Patients with Cutaneous Metastases from Solid Tumors

Background Cutaneous metastases (CMs) are a manifestation of advanced cancer and can be treated with oncolytic immunotherapy. Laboratory studies suggest radiotherapy (RT) may facilitate response to immunotherapy. We hypothesized that oncolytic immunotherapy with talimogene lapherparepvec (T-VEC, an oncolytic immunotherapy that expresses granulocyte–macrophage colony stimulating factor) and RT would produce response in non-targeted metastases. Methods A randomized phase 2 trial of T-VEC+/-RT was conducted. Eligible patients had ≥ 1 CM from a solid tumor amenable to T-VEC and RT and another measurable metastasis. Tumor and overall response was assessed using modified World Health Organization (mWHO) criteria. Adverse events and quality of life (QOL) were characterized using CTCAE v4.0 and Skindex-16, respectively. Correlative analyses of tumor genomics and immune system were performed. Results 19 patients were randomized to receive T-VEC (n = 9) or T-VEC+RT (n = 10). One patient in each arm demonstrated complete response in the largest non-targeted metastasis. The trial was closed after the first stage of enrollment because of no overall mWHO responses, slow accrual and the COVID19 pandemic. AEs were consistent with prior reports of T-VEC. Skin related QOL was poor before and after treatment. Median progression free survival was 1.2 and 2.5 months in the T-VEC and T-VEC+RT arms; median overall survival was 4.9 and 17.3 months in the T-VEC and T-VEC+RT arms. Analyses of peripheral blood cells and cytokines demonstrated responders exhibited several outlying lymphocyte and cytokine parameters. Conclusions Low overall response rate, slow accrual, and the COVID19 pandemic led to closure of this trial. Responses in non-injected and non-irradiated metastases were infrequent.