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Journal of Clinical Oncology, Vol 19, Issue 2 (January), 2001: 289-298
© 2001 American Society for Clinical Oncology

RAPID PUBLICATION

Phase II Trial of Intratumoral Administration of ONYX-015, a Replication-Selective Adenovirus, in Patients With Refractory Head and Neck Cancer

By J. Nemunaitis, F. Khuri, I. Ganly, J. Arseneau, M. Posner, E. Vokes, J. Kuhn, T. McCarty, S. Landers, A. Blackburn, L. Romel, B. Randlev, S. Kaye, D. Kirn

From US Oncology, Dallas, Baylor University Medical Center, Dallas, and M.D. Anderson Cancer Center, Houston, TX; Beatson Oncology Centre, Glasgow, Scotland; Albany Regional Cancer Center, Albany, NY; Dana-Farber Cancer Institute, Boston, MA; University of Chicago, Chicago, IL; and Onyx Pharmaceuticals, Inc, Richmond, CA.

Address reprint requests to John Nemunaitis, MD, US Oncology, 3535 Worth St, Collins Bldg, 5th Floor, Dallas, TX 75246; email John. Nemunaitis{at}USOncology.com

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 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.




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