Cretostimogene Grenadenorepvec Shows Complete Responses in NMIBC

Results from the phase 3 BOND-003 Cohort C trial (NCT04452591) evaluating cretostimogene grenadenorepvec monotherapy in patients with high-risk, Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without Ta/T1 disease, showed the trial met its primary end point, with 75.5% (95% CI, 66.3%-83.2%) of patients achieving a complete response (CR) at any time following treatment, according to a news release from the developer, CG Oncology.¹

What efficacy data did the final BOND-003 Cohort C analysis show?

The 12- and 24-month duration of response (DOR) rates were 64.2% (95% CI, 52.2%-73.8%) and 60.1% (95% CI, 48.2%-70.0%), respectively. Progression to MIBC was uncommon, with 96.6% of patients free from progression at both 48 and 96 weeks. Investigators reported meaningful responses among patients who had already received other therapies, including intravesical gemcitabine/docetaxel or systemic pembrolizumab (Keytruda), reflecting activity in a heavily pretreated population.

How durable were responses with cretostimogene grenadenorepvec?

The median DOR was at least 27.9 months, with findings ongoing, and approximately 90% of patients in response at 12 months remained in response at 24 months; 1 patient remained disease free beyond 51 months. Bladder preservation was maintained in approximately 89% of patients at 12 months and 81% at 24 months. An earlier interim analysis of Cohort C, presented at the 2025 American Urological Association Annual Meetingwith a March 2025 data cutoff, reported a 24-month CR rate of 42.3% by Kaplan-Meier estimation; the maturing data set now reflects longer follow-up and additional confirmed responses.²

“The results from BOND-003 represent a potential shift in this treatment paradigm, underpinned by encouraging durability of response and bladder preservation outcomes,” stated Mark D. Tyson II, MD, MPH, of Mayo Clinic and lead BOND-003 investigator, in the news release.¹ “With a clinically meaningful median [DOR] of 27.9 months...paired with approximately 89% of patients maintaining their bladders at 12 months and 81% at 24 months, we are seeing evidence of sustained bladder preservation without compromising the window for further therapeutic options, if needed.”

What safety and administration data were reported?

No grade 3 or greater treatment-related adverse effects (AEs), treatment-related discontinuations, or treatment-related deaths were reported. The median time to resolution of related AEs was 1 day (IQR, 0-7). The most common treatment-related AEs occurring in at least 10% of patients were bladder spasms, pollakiuria, micturition urgency, dysuria, and hematuria.

Cretostimogene grenadenorepvec is administered intravesically in an office-based setting and does not require prophylactic medication, operating room time, additional cystoscopy, or anesthesia, aligning with existing American Urological Association/Society of Urologic Nurses and Associates intravesical administration policy.

How was the BOND-003 trial designed?

BOND-003 is a single-arm, open-label, phase 3 trial that enrolled a total of 112 patients with high-risk, BCG-unresponsive NMIBC across sites in North America, Australia, and the Asia-Pacific region. Eligible patients had pathologically confirmed high-risk NMIBC with CIS, with or without Ta or T1 disease, that was unresponsive to prior BCG therapy; an ECOG performance status of 0 to 2; and adequate organ function.³ Patients had to be ineligible for or have refused radical cystectomy. Cretostimogene grenadenorepvec was administered intravesically once weekly for 6 weeks, with an additional 6-week induction cycle for patients with persistent high-grade disease at week 13.

The primary end point was CR at any time. Secondary end points included DOR, recurrence-free survival, progression-free survival, overall survival, and safety.

“The BOND-003 Cohort C data demonstrate cretostimogene's favorable efficacy and best-in-disease durability,” Vijay Kasturi, MD, chief medical officer of CG Oncology, said in the news release.¹ “Importantly, we also observed a very low rate of progression to [MIBC], with only 3.4% of patients progressing during the study.”

Cretostimogene grenadenorepvec has previously received FDA fast track and breakthrough therapy designations for high-risk, BCG-unresponsive NMIBC. Beyond BOND-003, the agent is also being evaluated in the phase 3 PIVOT-006 trial (NCT06111235) in intermediate-risk NMIBC and the phase 2 CORE-008 trial (NCT06567743) in high-risk NMIBC; it is also available to certain patients with BCG-unresponsive disease in North America through an expanded access program.

References

1. CG Oncology announces publication of pivotal Phase 3 BOND-003 Cohort C study results in The Lancet Oncology. News release. CG Oncology, Inc. July 27, 2026. Accessed July 28, 2026. https://tinyurl.com/59du9e5z
2. CG Oncology announces best-in-disease durability data in BOND-003 Cohort C and promising early signal in Cohort P for cretostimogene grenadenorepvec at the American Urological Association Annual Meeting. News release. CG Oncology, Inc. April 26, 2025. Accessed July 28, 2026. https://tinyurl.com/444ryn43
3. Study of cretostimogene given in patients with non-muscle invasive bladder cancer, unresponsive to Bacillus-Calmette-Guerin (BOND-003). ClinicalTrials.gov. Updated July 10, 2026. Accessed July 28, 2026. https://tinyurl.com/mrx73amm