A Phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer

An E1B 55 kDa gene-deleted adenovirus, Onyx-015, which reportedly selective ly replicates in and lyses p53-deficient cells, was administered by a singl e intratumoral injection to a total of 22 patients with recurrent head and neck cancer. The objectives of this Phase I study were to determine the saf ety, feasibility, and efficacy of this therapy and determine any correlatio n to p53 status. Six cohorts were investigated with a dose escalation from 10(7)-10(11) plaque-forming units. Toxicity was assessed using NCIC criteri a. Tumor response was assessed by clinical and radiological measurement. Bl ood samples were taken to detect adenovirus DNA and neutralizing antibody t o adenovirus, Tumor biopsies were taken to detect adenovirus by iii situ hy bridization. Treatment was well tolerated, with the main toxicity being gra de 1/2 flu-like symptoms. Dose-limiting toxicity was not reached at the hig hest dose of 10(11) plaque-forming units. Twenty-one of the 22 patients tre ated showed an increase in neutralizing antibody to adenovirus, In situ hyb ridization showed viral replication in 4 of 22 patients treated, all of who m had mutant p53 tumors, Using conventional response criteria, no objective responses were observed. However, magnetic resonance imaging scans were su ggestive of tumor necrosis at the site of viral injection in five patients, three of whom were classified using nonconventional criteria as partial re sponders, and two of whom were classified using nonconventional criteria as minor responders. Of these five cases, four had mutant p53 tumors. The res ponse duration for the three partial responders was 4, 8, and 12 weeks. An additional eight patients had stable disease in the injected tumors lasting from 4-8 weeks, These preliminary results show that intratumoral administr ation of Onyx-015 is feasible, well tolerated, and associated with biologic al activity. Further investigation of Onyx-015, particularly with a more fr equent injection protocol and in combination with systemic chemotherapy, is warranted.