Data from the Phase 3 BOND-003 study indicate that cretostimogene monotherapy demonstrates a 75.2% complete response (CR) rate in patients with high-risk non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette Guerin (BCG) treatment. The results, presented at the 2024 American Urological Association (AUA) Annual Meeting, suggest a potential new treatment option for patients with limited alternatives.
Efficacy of Cretostimogene
The BOND-003 study (NCT04452591), a single-arm, Phase 3 trial, evaluated cretostimogene in patients with high-risk BCG-unresponsive NMIBC with carcinoma in-situ (CIS), with or without Ta or T1 papillary tumors. As of the April 1, 2024, cutoff date, 79 out of 105 patients (75.2% [95% CI, 65-83]) achieved a complete response at any time. Furthermore, 29 patients maintained a complete response for 12 months or more, with ongoing response evaluations for 22 patients. The median duration of response (DOR) was not reached. Cystectomy-free survival was observed in 92.4% of patients, and none of the patients with a complete response underwent radical cystectomy or showed nodal or metastatic progression.
Safety Profile
The study reported a favorable safety profile for cretostimogene. There were no Grade 3 or higher treatment-related adverse events (TRAEs) or deaths reported. Two patients (1.8%) experienced serious TRAEs (Grade 2), and no treatment-related discontinuation of cretostimogene was observed. The most common TRAEs (≥10%) included bladder spasm, pollakiuria, dysuria, micturition urgency, and hematuria.
Expert Commentary
Gary D. Steinberg, M.D., Professor in the Department of Urology at Rush University Medical Center, noted, "The positive 12-month BOND-003 data presented at AUA 2024, with a notable duration of response, reinforces cretostimogene monotherapy as a potential backbone therapy in the NMIBC treatment landscape for BCG-unresponsive patients... This innovative immunotherapy candidate may, if approved, emerge as a favored option for patients over the surgical extraction of their bladder, as they face limited options."
Regulatory Status and Future Directions
Cretostimogene has been granted both Fast Track Designation and Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for high-risk BCG-unresponsive NMIBC with carcinoma in-situ with or without Ta or T1 papillary tumors. Topline data from BOND-003 is expected by the end of 2024, with a regulatory approval submission anticipated thereafter. The fully enrolled global trial, which includes 112 patients, is ongoing in North America and the Asia-Pacific region.
