Phase 1 study of oncolytic virus VV1 as monotherapy or in combination with avelumab in patients with relapsed refractory solid tumors

PURPOSE: VV1 is designed to induce selective oncolysis of tumor cells, and to amplify cellular antitumor immune responses. This open-label, phase 1, multicenter clinical trial assessed the safety and tolerability of VV1 monotherapy administered intratumorally (IT) or IV or administered IV in combination with avelumab. PATIENTS AND METHODS: Patients with advanced solid tumors received IT (n=27) or IV VV1 monotherapy (n=33) or IV VV1 plus avelumab (n=16). Infusion durations (15180 min) and viral dose (1.7 x 1010 or 1.0 x 1011 TCID50) were also evaluated. Study objectives included VV1 safety and tolerability, pharmacokinetics, pharmacodynamics, preliminary efficacy and immune responses. RESULTS: IT and IV VV1 was well tolerated and injection reactions were infrequent. The most common adverse events of any grade related to VV1 were cytokine release syndrome (58%), fatigue (33%) and decreased lymphocyte count (32%). Virus infection of tumors was confirmed using NIS imaging and increases in serum levels of virally encoded interferon-β. Histological tumor analysis at 28 days post-IT VV1 administration indicated increases in tumor infiltrating immune cells. Two durable partial responses were recorded: a patient with pheochromocytoma after one IV dose of VV1 and a patient with thymic cancer in the combination arm. Stable disease was observed in 17 of 49 patients (34.7%) who received IV VV1. CONCLUSIONS: This first-in-human study demonstrates that IT or IV VV1 administration had an acceptable safety profile as monotherapy and IV in combination with avelumab. There is preliminary antitumor activity. IT VV1 plus cemiplimab is now showing promise in the neoadjuvant setting.