An open label, single-arm, phase II multicenter study of the safety and efficacy of CG0070 oncolytic vector regimen in patients with BCG-unresponsive non–muscle-invasive bladder cancer: Interim results

• Published in: Urologic oncology 2018-10, Vol.36 (10), p.440-447
• Main Authors: Packiam, Vignesh T., Lamm, Donald L., Barocas, Daniel A., Trainer, Andrew, Fand, Benjamin, Davis, Ronald L., Clark, William, Kroeger, Michael, Dumbadze, Igor, Chamie, Karim, Kader, A. Karim, Curran, Dominic, Gutheil, John, Kuan, Arthur, Yeung, Alex W., Steinberg, Gary D.
• Format: Article
• Language: English
• Subjects: Adenoviridae; Administration, Intravesical; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; BCG unresponsive; Carcinoma, Transitional Cell - therapy; Female; Humans; Intravesical therapy; Male; Middle Aged; Non-muscle invasive bladder cancer; Oncolytic adenovirus; Oncolytic Virotherapy - adverse effects; Oncolytic Virotherapy - methods; Oncolytic Viruses; Urinary Bladder Neoplasms - therapy
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2017.07.005

CG0070 is a replication-competent oncolytic adenovirus that targets bladder tumor cells through their defective retinoblastoma pathway. Prior reports of intravesical CG0070 have shown promising activity in patients with high-grade non–muscle invasive bladder cancer (NMIBC) who previously did not respond to bacillus Calmette-Guérin (BCG). However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy. At interim analysis (April 2017), 45 patients with residual high-grade Ta, T1, or carcinoma-in-situ (CIS) ± Ta/T1 had evaluable 6-month follow-up in this phase II single-arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies. Of 45 patients, there were 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, 3 T1. Overall 6-month CR (95% CI) was 47% (32%–62%). Considering 6-month CR for pathologic subsets, pure CIS was 58% (37%–78%), CIS ± Ta/T1 50% (33%–67%), and pure Ta/T1 33% (8%–70%). At 6 months, the single patient that progressed to muscle-invasive disease had Ta and T1 tumors at baseline. No patients with pure T1 had 6-month CR. Treatment–related adverse events (AEs) at 6 months were most commonly urinary bladder spasms (36%), hematuria (28%), dysuria (25%), and urgency (22%). Immunologic treatment–related AEs included flu-like symptoms (12%) and fatigue (6%). Grade III treatment–related AEs included dysuria (3%) and hypotension (1.5%). There were no Grade IV/V treatment–related AEs. This phase II study demonstrates that intravesical CG0070 yielded an overall 47% CR rate at 6 months for all patients and 50% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS. •Overall 6-month complete response rate of 47% in patients with high-risk BCG-unresponsive NMIBC.•A 58% 6-month complete response in patients with pure CIS; 50% 6-month complete response for patients with CIS-containing tumors.•Overall toxicity was accept