Safety and feasibility of injection with an E1B-55 kDa gene-deleted, replication-selective adenovirus (ONYX-015) into primary carcinomas of the pancreas: a phase I trial.

Novel therapies are needed for locally advanced pancreatic carcinoma. ONYX-015 (dl1520) is an E1B-55 kDa region-deleted adenovirus that selectively replicates in and lyses tumor cells with abnormalities in p53 function (eg gene mutation). We carried out a phase I dose escalation study of ONYX-015 in patients with unresectable pancreatic cancer. ONYX-015 was administered via CT-guided injection (n = 22 patients) or intraoperative injection (n = 1) into pancreatic primary tumors every 4 weeks until tumor progression. Interpatient dose escalation was carried out with at least three patients per dose level from 10(8) p.f.u. up to the 10(11) p.f.u. dose level (two patients treated at this dose). The majority of patients had abnormally low cellular immunity (CD4 counts and hypersensitivity skin testing). Injection of ONYX-015 into pancreatic carcinomas was well-tolerated. Mild, transient pancreatitis was noted in only one patient. Dose-escalation proceeded to the highest dose level. Neutralizing antibodies rose post-treatment in all patients. After injection, ONYX-015 was detectable in the blood 15 min later, but not between 1 and 15 days later. Viral replication was not documented, however, in contrast to trials in other tumor types. No objective responses were demonstrated. Intratumoral injection of an E1B-55 kDa region-deleted adenovirus into primary pancreatic tumors was feasible and well-tolerated at doses up to 10(11) p.f.u. (2 x 10(12) particles), but viral replication was not detectable.