Clinical research results with dl1520 (Onyx-015), a replication-selective adenovirus for the treatment of cancer: what have we learned?

Replication-selective microbial agents hold promise as a novel cancer treat ment platform, dl1520 (Onyx-015), an E1B-55 kD gene-deleted adenovirus, was the first such genetically engineered agent to be tested in humans. Over 2 00 cancer patients have been treated to date on over 10 clinical trials (ph ases I-III). The virus was generally well-tolerated at doses of up to 2 x 1 0(12) particles by intratumoral, intraperitoneal, hepatic arterial and intr avenous administration; no maximally tolerated doses were identified by any route of administration. Viral replication was tumor-selective, and was do cumented after administration by all routes; replication was generally tran sient (<10 days), however, and was variable depending on tumor histology. S ingle agent efficacy has been limited to date (0-14% local tumor regression rates). In combination with chemotherapy, however, encouraging antitumoral activity has been demonstrated. These clinical research results demonstrat e the potential of this novel treatment platform, as well as the hurdles to be overcome. Novel replication-selective agents with improved potency are needed.