A First in Human Phase 1 Study of CG0070, a GM-CSF Expressing Oncolytic Adenovirus, for the Treatment of Nonmuscle Invasive Bladder Cancer

作者：Burke James M^*; Lamm Donald L; Meng Maxwell V; Nemunaitis John J; Stephenson Joseph J; Arseneau James C; Aimi Junko; Lerner Seth; Yeung Alex W; Kazarian Troy; Maslyar Daniel J; McKiernan James M

来源：Journal of Urology, 2012, 188(6): 2391-2397.

DOI：10.1016/j.juro.2012.07.097

• urinary bladder
• urinary bladder neoplasms
• Adenoviridae
• dose-response relationship, immunologic
• toxicity

Purpose: We assessed the safety, pharmacokinetics and anticancer activity of intravesical CG0070, a cancer selective, replication competent adenovirus, for the treatment of nonmuscle invasive bladder cancer. %26lt;br%26gt;Materials and Methods: A total of 35 patients received single or multiple (every 28 days x 3 or weekly x 6) intravesical infusions of CG0070 at 1 of 4 dose levels (1 x 10(12), 3 x 10(12), 1 x 10(13) or 3 x 10(13) viral particles). Response to treatment was based on cystoscopic assessment and biopsy or urine cytology. Urine and plasma CG0070, and granulocyte-monocyte colony-stimulating factor were measured in all patients. A subset of 18 patients was assessed for retinoblastoma phosphorylation status. %26lt;br%26gt;Results: Grade 1-2 bladder toxicities were the most common adverse events observed. A maximum tolerated dose was not reached. High levels of granulocyte-monocyte colony-stimulating factor were detected in urine after administration in all patients. Virus replication was suggested based on an increase in urine CG0070 genomes between days 2 and 5 in 58.3% of tested patients (7 of 12). The complete response rate and median duration of the complete response across cohorts was 48.6% and 10.4 months, respectively. In the multidose cohorts the complete response rate for the combined groups (every 28 days and weekly x 6) was 63.6% (14 of 22 patients). In an exploratory, retrospective assessment patients with borderline or high retinoblastoma phosphorylation who received the multidose schedules had an 81.8% complete response rate (9 of 11). %26lt;br%26gt;Conclusions: Intravesical CG0070 was associated with a tolerable safety profile and antibladder cancer activity. Granulocyte-monocyte colony-stimulating factor transgene expression and CG0070 replication were also suggested.

• 出版日期2012-12