Cretostimogene Shows Promise in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer
核心洞察
Phase 3 trial of cretostimogene grenadenorepvec shows a 75.7% complete response rate in patients with high-risk BCG-unresponsive NMIBC.
The 3- and 6-month landmark complete response rates were 68.2% and 63.6%, respectively, indicating sustained efficacy over time.
The oncolytic immunotherapy was generally well-tolerated, with mostly low-grade genitourinary adverse events and no treatment discontinuations.
CG Oncology's cretostimogene grenadenorepvec monotherapy has demonstrated a 75.7% complete response rate at any time in patients with high-risk Bacillus Calmette-Guerin (搜索) (BCG)-unresponsive non-muscle invasive bladder cancer (搜索) (NMIBC), according to Phase 3 BOND-003 clinical trial data. The findings, presented at the 24th Annual Meeting of the Society of Urological Oncology (SUO), suggest a promising non-surgical option for patients with recurrent bladder cancer (搜索).
The BOND-003 trial (NCT04452591) is a single-arm, Phase 3 study evaluating the efficacy and safety of cretostimogene grenadenorepvec in patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ with or without Ta/T1 disease. The trial, which is fully enrolled with 116 patients across North America and the Asia-Pacific region, has a primary endpoint of complete response (CR) at any time, with duration of response measured as a secondary endpoint.
Key Efficacy Results
As of the October 5, 2023, data cutoff, 66 patients were evaluable for efficacy with a minimum of 3-month follow-up. The data showed:
- 75.7% of patients (50/66) achieved a complete response at any time.
- The 3- and 6-month landmark CR rates were 68.2% (45/66) and 63.6% (42/66), respectively.
Safety and Tolerability
The adverse events observed were consistent with prior studies, with the treatment generally well-tolerated. The most common treatment-related adverse events (AEs) reported included transient grade 1-2 local genitourinary symptoms. No grade 3 or higher AEs related to cretostimogene grenadenorepvec were observed, and there were no treatment discontinuations due to AEs.
Implications for Bladder Cancer Treatment
"The positive BOND-003 initial results demonstrate the impact of cretostimogene in BCG-unresponsive disease patients as a promising new monotherapy which may lead to profoundly meaningful non-surgical outcomes for those with recurrent bladder cancer (搜索)," said Trinity J. Bivalacqua, M.D., Ph.D., Professor of Urology and Oncology at the Perelman Center for Advanced Medicine, University of Pennsylvania. "NMIBC has been a difficult disease to treat, and patients have often had no options except surgical removal of the bladder."
About Cretostimogene Grenadenorepvec
Cretostimogene grenadenorepvec is an investigational, intravesically delivered oncolytic immunotherapy. It is also being evaluated in a Phase 2 clinical trial (CORE-001) in combination with pembrolizumab for BCG-unresponsive NMIBC and in an investigator-sponsored clinical trial in combination with nivolumab for muscle invasive bladder cancer (搜索).
Bladder Cancer Statistics
More than 82,000 people are estimated to be diagnosed with bladder cancer (搜索) in 2023. NMIBC is the most common form of bladder cancer, representing approximately 75% of newly diagnosed cases. Bladder cancer is the sixth most common form of cancer in the United States, and men account for three quarters of newly diagnosed cases.
CG Oncology's Perspective
"We are thrilled to present this data at SUO, and we look forward to further discussions with the FDA on advancing cretostimogene grenadenorepvec as a potential new therapy for bladder cancer (搜索) patients at significant risk of disease recurrence and progression," said Arthur Kuan, Chief Executive Officer, CG Oncology. "Our goal is to transform the treatment landscape for patients with bladder cancer, and these results reinforce our commitment to developing bladder-sparing therapeutics to improve patient outcomes and quality of life."