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 1011 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 after injection during cycle 1, and no patients had evidence of replication> 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.© 2001 by American Society of Clinical Oncology.