PMID- 28755959 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20181211 IS - 1873-2496 (Electronic) IS - 1078-1439 (Linking) VI - 36 IP - 10 DP - 2018 Oct TI - 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. PG - 440-447 LID - S1078-1439(17)30350-2 [pii] LID - 10.1016/j.urolonc.2017.07.005 [doi] AB - OBJECTIVES: 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-Guerin (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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Packiam, Vignesh T AU - Packiam VT AD - Section of Urology, Department of Surgery, University of Chicago, Chicago, IL. Electronic address: vignesh.packiam@uchospitals.edu. FAU - Lamm, Donald L AU - Lamm DL AD - BCG Oncology, P.C., Phoenix, AZ. FAU - Barocas, Daniel A AU - Barocas DA AD - Department of Urologic Oncology, Vanderbilt University, Nashville, TN. FAU - Trainer, Andrew AU - Trainer A AD - Adult Pediatric Urology & Urogynecology, P.C., Omaha, NE. FAU - Fand, Benjamin AU - Fand B AD - Premier Urology Group, LLC, Edison, NJ. FAU - Davis, Ronald L 3rd AU - Davis RL 3rd AD - Department of Urology, Wake Forest University, Winston-Salem, NC. FAU - Clark, William AU - Clark W AD - Alaska Urological Institute, Anchorage, AK. FAU - Kroeger, Michael AU - Kroeger M AD - University of Nebraska Medical Center, Omaha, NE. FAU - Dumbadze, Igor AU - Dumbadze I AD - Tri State Urologic Services, Cincinnati, OH. FAU - Chamie, Karim AU - Chamie K AD - Department of Urology, University of California Los Angeles, Los Angeles, CA. FAU - Kader, A Karim AU - Kader AK AD - Department of Urology, University of California San Diego, San Diego, CA. FAU - Curran, Dominic AU - Curran D AD - Cold Genesys, Inc., Santa Ana, CA. FAU - Gutheil, John AU - Gutheil J AD - SciQuus Oncology, La Jolla, CA. FAU - Kuan, Arthur AU - Kuan A AD - Cold Genesys, Inc., Santa Ana, CA. FAU - Yeung, Alex W AU - Yeung AW AD - Cold Genesys, Inc., Santa Ana, CA. FAU - Steinberg, Gary D AU - Steinberg GD AD - Section of Urology, Department of Surgery, University of Chicago, Chicago, IL. LA - eng PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20170726 PL - United States TA - Urol Oncol JT - Urologic oncology JID - 9805460 RN - 0 (Antineoplastic Agents) SB - IM MH - Adenoviridae MH - Administration, Intravesical MH - Aged MH - Aged, 80 and over MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Carcinoma, Transitional Cell/*therapy MH - Female MH - Humans MH - Male MH - Middle Aged MH - Oncolytic Virotherapy/adverse effects/*methods MH - Oncolytic Viruses MH - Urinary Bladder Neoplasms/*therapy OTO - NOTNLM OT - BCG unresponsive OT - Intravesical therapy OT - Non-muscle invasive bladder cancer OT - Oncolytic adenovirus EDAT- 2017/08/02 06:00 MHDA- 2018/12/12 06:00 CRDT- 2017/07/31 06:00 PHST- 2017/04/14 00:00 [received] PHST- 2017/06/14 00:00 [revised] PHST- 2017/07/01 00:00 [accepted] PHST- 2017/08/02 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2017/07/31 06:00 [entrez] AID - S1078-1439(17)30350-2 [pii] AID - 10.1016/j.urolonc.2017.07.005 [doi] PST - ppublish SO - Urol Oncol. 2018 Oct;36(10):440-447. doi: 10.1016/j.urolonc.2017.07.005. Epub 2017 Jul 26.