Phase 1 trial of intravenous VCN-01 oncolytic adenovirus and durvalumab for metastatic HNSCC refractory to immunotherapy

VCN-01 is a hyaluronidase-expressing oncolytic adenovirus that increased immune checkpoint antibody in murine tumors. A multicenter phase 1 trial in Spain evaluated VCN-01 with durvalumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) refractory to anti-PD-(L)1. Patients received 3.3E12 viral particles (low dose; LD) or 1.0E13 viral particles (high dose, HD) plus durvalumab 1500 mg once every 4 weeks concomitantly (VCN-01 and durvalumab on day 1; arm I) or sequentially (VCN-01 on day -14 and durvalumab on day 1; arm II). Six patients were enrolled in arm I LD, eight in arm II LD, and six in arm II HD. Two dose-limiting toxicities occurred in arm I LD, one in arm II LD, and none in arm II HD. Antitumor responses were observedm with arm II HD displaying the numerically longest median overall survival of 17.3 months (95% CI 8.1-NE). Eleven patients (61.1%) were alive longer than 12 months. VCN-01 was detected in blood and tumors, and hyaluronidase expression was confirmed. Changes in tumor immune markers were identified, including increased PD-L1 expression correlating with overall survival. The authors conclude that sequential VCN-01 plus durvalumab was better tolerated than concomitant treatment. The recommended phase 2 dose was 1.0E13 viral particles on the sequential schedule. Encouraging survival was observed in R/M HNSCC patients refractory to anti-PD-(L)1 agents.