Phase II trial of intratumoral administration of ONYX-015, a replication-selective adenovirus, in patients with refractory head and neck cancer

Purpose: To determine the safety, humoral immune response replication, and activity of multiple intratumoral injections of ONYX-015 (replication selective adenovirus) in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: This phase II trial enrolled patients with SCCHN who had recurrence/relapse after prior conventional treatment. Patients received ONYX-015 at a dose of 2 x 10(11) particles via intratumoral injection for either 5 consecutive days (standard) or twice daily for 2 consecutive weeks (hyperfractionated) during a 21-day cycle. Patients were monitored for tumor response, toxicity, and antibody formation. Results: forty patients (30 standard and 10 hyperfractionated) received 533 injections of ONYX-015. Standard treatment resulted in 14% partial to complete regression, 41% stable disease, and 45% progressive disease rates, Hyperfractionated treatment resulted in 10% complete response, 62% stable disease, and 29% progressive disease rates, Treatment-related toxicity included mild to moderate fever (67% overall) and injection site pain (47% on the standard regimen, 80% on the hyperfractionated regimen). Detectable circulating ONYX-015 genome suggestive of intratumoral replication was identified in 41% of tested patients on days 5 and 6 of cycle 1;9% of patients had evidence of viral replication 10 days alter injection during cycle 1, and no patients had evidence of replication greater than or equal to 22 days after injection, Conclusion: ONYX-015 can be safely administered via intratumoral injection to patients with recurrent/ refractory SCCHN. ONYX-015 viremia is transient. Evidence of modest antitumoral activity is suggested. J Clin Oncol 19:289-298. (C) 2001 by American Society of Clinical Oncology.