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 re plicates in and lyses tumor cells with abnormalities in p53 function leg ge ne mutation). We carried out a phase I dose escalation study of ONYX-015 in patients with unresectable pancreatic cancer. ONYX-015 was administered vi a CT-guided injection (n = 22 patients) or intraoperative injection (n = 1) into pancreatic primary tumors every 4 weeks until tumor progression. Inte rpatient dose escalation was carried out with at least three patients per d ose level from 10(8) p.i.u. up to the 10(11) p.f.u. dose level (two patient s treated at this dose). The majority of patients had abnormally low cellul ar immunity (CD4 counts and hypersensitivity skin testing). Injection of ON YX-015 into pancreatic carcinomas was well-tolerated. Mild, transient pancr eatitis was noted in only one patient. Dose-escalation proceeded to the hig hest dose level. Neutralizing antibodies rose post-treatment in all patient s. 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, howe ver, in contrast to trials in other tumor types. No objective responses wer e demonstrated Intratumoral injection of an E1B-55 kDa region-deleted adeno virus into primary pancreatic tumors was feasible and well-tolerated at dos es up to 10(11) p.f.u. (2 x 10(12) particles), but viral replication was no t detectable.