CG Oncology's cretostimogene grenadenorepvec, an oncolytic immunotherapy, has demonstrated promising results in patients with high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). Topline data from the Phase 3 BOND-003 trial, presented at the Society of Urologic Oncology (SUO) 25th Annual Meeting, revealed a 74.5% complete response (CR) rate at any time point after treatment with cretostimogene as a single agent.
The BOND-003 trial (NCT04452591) is a single-arm, Phase 3 study evaluating cretostimogene monotherapy in patients with high-risk BCG-unresponsive NMIBC. The trial enrolled 112 patients with carcinoma in-situ (CIS) with or without Ta or T1 papillary tumors across North America and the Asia-Pacific region. The primary endpoint was CR at any time, with duration of response (DOR) as a secondary endpoint.
Sustained and Durable Responses
The median duration of response has not been reached but exceeds 27 months as of the data cutoff of September 30, 2024. According to Gary D. Steinberg, M.D., Professor, Department of Urology at Rush University Medical Center, the BOND-003 study demonstrates cretostimogene’s compelling efficacy as well as its ability to induce a best-in-class durable response in NMIBC patients, with 56.6% of patients remaining in response at 24 months or greater, by K-M estimate.
Safety and Tolerability
Importantly, the treatment was well-tolerated, with no Grade 3 or greater treatment-related adverse events (TRAEs) or deaths reported. The most common TRAEs (≥10%) were bladder spasm, pollakiuria, micturition urgency, dysuria, and hematuria. No treatment-related discontinuation of cretostimogene was observed, and 97.3% of patients completed all expected treatments, demonstrating favorable patient adherence and compliance.
Impact on Disease Progression
Data also showed that 97.3% of patients were free from progression to Muscle Invasive Bladder Cancer (MIBC) at 12 months, suggesting a significant impact on preventing disease advancement.
Regulatory Designations
Cretostimogene has received FDA Fast Track and Breakthrough Therapy Designations for BCG-Unresponsive, high-risk NMIBC patients with CIS, underscoring the unmet need and the therapy's potential to address it.
Ongoing Research and Expanded Access Program
CG Oncology has also initiated an Expanded Access Program for cretostimogene in North America for patients who are unresponsive to BCG and meet certain program eligibility requirements. This program aims to gather real-world data from diverse patient populations and address access issues while the drug undergoes FDA approval.
Sarah Psutka, MD, MS, Urologic Oncologist, Associate Professor of Urology, Department of Urology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, examines the expanded access program (EAP) for cretostimogene in BCG-unresponsive bladder cancer. The conversation highlights how this oncolytic immunotherapy, which shows a 74% complete response rate and strong durability, is being made available through an EAP designed to gather real-world data from diverse patient populations. Dr. Psutka emphasizes the program's broad eligibility criteria and its potential to address access issues while collecting prospective data on safety, efficacy, and patient-reported outcomes in underrepresented populations.
