BOND-003: Cretostimogene yields durable 24-month responses in high-grade NMIBC

Treatment of high-grade, BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with the investigational oncolytic immunotherapy cretostimogene grenadenorepvec is associated with a high anytime complete response (CR) rate as well as duration of response, according to data presented at the 2025 Society of Urologic Oncology (SUO) Annual Meeting in Phoenix, Arizona.¹

The data presented at SUO 2025 came from cohort C of the phase 3 BOND-003 trial (NCT04452591) evaluating cretostimogene in patients with high-grade, BCG-responsive NMIBC. The authors were led by Mark D. Tyson II, MD, MPH, a urologic oncologist with Mayo Clinic in Phoenix.

A total of 112 patients with high-grade, BCG-unresponsive NMIBC with carcinoma in situ (CIS) +/– Ta/T1 disease were enrolled for the study, and efficacy data were available for 110 patients. Prior to treatment, all visible disease was resected in each patient. Patients received cystoscopy, along with biopsy as indicated, as well as cytology every 3 months for the first 2 years and then every 6 months starting in year 3. Of the cohort, 74% were male, 62% were White, and 83% were older than 65 years of age.

Treatment was administered in an induction phase consisting of 6 weekly doses, “followed by 3 weekly maintenance cycles at months 3, 6, 9, 12 and 18,” according to the abstract. Patients could undergo re-induction at month 3 if biopsy indicated persistent high-grade Ta or CIS. The primary end point of the study was CR at any time. Duration of response (DoR), recurrence-free survival, progression-free survival, cystectomy-free survival, safety, and tolerability comprised the secondary end points.

At a median follow-up of 25.8 months, the CR rate at any time was 75.5% (83/110 patients; 95% CI, 66.3-83.2). At 12 months, CR rate was 46.4% (51/110 patients; 95% CI, 36.9-56.1); 12-month CR rate by Kaplan-Meier estimate was 50.7% (95% CI, 40.9-59.8). The 24-month CR rate was 41.8% (46/110 patients; 95% CI, 32.5-51.6); the 24-month CR rate by Kaplan-Meier estimate was 42.4% (95% CI, 32.7-51.7). The investigators noted that 106 (96.4%) patients were free from progression to T2 or higher disease. Additionally, 92 (83.6%) patients did not receive radical cystectomy post recurrence or progression.

Median ongoing DoR was 27.9 months (95% CI, 14.3-NE). The investigators reported that the estimated DoR probability at 12 months was 64.2% (95% CI, 52.5-73.8); the estimated DoR probability at 24 months was 60.1% (95% CI, 48.2-70.0).

Regarding safety, incidence of 1 or more treatment-related adverse event (TRAE) of any grade was observed in 71 (63.4%) patients. No grade 3 or higher TRAEs were observed in the cohort. TRAEs of any grade occurring in more than 20% of patients included bladder spasm in 28 (25%) patients, pollakiuria in 25 (22.3%) patients, and urgency in 23 (20.5%) patients. None of these TRAEs were grade 3 or higher. The investigators also noted that the median time to TRAE resolution was 1 day.

The investigators also noted a high degree of adherence to treatment. There were no treatment discontinuations. The missed-dose rate was 1.8%, and the delayed-dose rate was 7.1%.

“Cretostimogene offers distinct advantages with its efficacy, durability, and safety profile for the treatment of [high-grade, BCG-unresponsive] NMIBC,” the authors wrote in their abstract.

The FDA has granted cretostimogene fast track and breakthrough therapy designations for BCG-unresponsive NMIBC with CIS +/– Ta/T1 disease. Developer CG Oncology previously announced that it plans to initiate a biologics license application to the FDA for the indication of high-grade, BCG-unresponsive NMIBC in Q4 this year.²

REFERENCES

1. Tyson MD, Uchio EM, Nam J-K, et al. Durable 24-month outcomes from BOND-003 Cohort C: phase 3 study of intravesical cretostimogene grenadenorepvec for high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Abstract 53. https://suo-abstracts.secure-platform.com/a/gallery/rounds/24/details/4394

2. CG Oncology continues to demonstrate best-in-disease durability and tolerability in BOND-003 cohort C; additional 12 patients in complete response at 24 months. News release. CG Oncology Inc. September 5, 2025. Accessed December 3, 2025. https://www.globenewswire.com/news-release/2025/09/05/3145193/0/en/CG-Oncology-Continues-to-Demonstrate-Best-in-Disease-Durability-and-Tolerability-in-BOND-003-Cohort-C-Additional-12-Patients-in-Complete-Response-at-24-Months.html