Selective replication and oncolysis in p53 mutant tumors with ONYX-015, anE1B-55kD gene-deleted adenovirus, in patients with advanced head and neck cancer: A Phase II trial

ONYX-015 is an E1B-55kDa gene-deleted adenovirus engineered to selectively replicate in and lyse p53-deficient cancer cells. To evaluate the selectivi ty of ONYX-015 replication and cytopathic effects for the first time in hum ans, we carried out a Phase II clinical testing of intratumoral and peritum oral ONYX-015 injection in 37 patients with recurrent head and neck carcino ma. Patients received ONYX-015 at a daily dose of 1 x 10(10) plaque-forming units (pfu) via intratumoral injection for 5 days during week 1 of each 3- week cycle (n = 30; cohort A), or 1 x 10(10) pfu twice a day for 10 days du ring weeks 1 and 2 of each 3-week cycle. Posttreatment biopsies documented selective ONYX-015 presence and/or replication in the tumor tissue of 7 of 11 patients biopsied on days 5-14, but not in immediately adjacent normal t issue (0 of 11 patients; P = 0.01), Tissue destruction was also highly sele ctive; significant tumor regression (>50%) occurred in 21% of evaluable pat ients, whereas no toxicity to injected normal peritumoral tissues was demon strated. p53 mutant tumors were significantly more likely to undergo ONYX-0 15-induced necrosis (7 of 12) than were p53 wild-type tumors (0 of 7; P = 0 .017), High neutralizing antibody titers did not prevent infection and/or r eplication within tumors. ONYX-015 is the first genetically engineered repl ication-competent virus to demonstrate selective intratumoral replication a nd necrosis in patients. This agent demonstrates the promise of replication -selective viruses as a novel therapeutic platform against cancer.