Durable Responses Seen With Cretostimogene in BCG-Unresponsive NMIBC

Cretostimogene grenadenorepvec, an investigational intravesical oncolytic immunotherapy, produced durable complete responses and high rates of bladder preservation in patients with high-risk, Bacillus Calmette Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ, according to results from cohort C of the pivotal phase 3 BOND-003 trial (NCT04452591) published in The Lancet Oncology.^1,2

The single-arm trial met its primary end point of complete response (CR) at any time, exceeding historic and contemporary benchmarks in this setting. Specifically, patients treated with cretostimogene monotherapy achieved a CR rate of 75.5% (95% CI, 66.3%-83.2%).

Responses were durable over time, with 12- and 24-month duration of response (DOR) rates reaching 64.2% (95% CI, 52.2%-73.8%) and 60.1% (95% CI, 48.2%-70.0%), respectively. The median DOR was at least 27.9 months and had not been reached at data cutoff, with approximately 90% of patients in response at 12 months remaining in durable response at 24 months; 1 patient remained disease-free beyond 51 months.

“These results are particularly encouraging given BOND-003 enrolled a heavily pretreated population representative of the patients that clinicians often encounter in real-world practice. Specifically, we observed meaningful responses in patients who had already received other therapies, including intravesical gemcitabine-docetaxel or systemic pembrolizumab [Keytruda], underscoring cretostimogene's activity across a clinically diverse and difficult-to-treat patient population,” Mark D. Tyson, MD, MPH, professor of urology at Mayo Clinic and lead author of the publication, stated in a news release.¹ “If approved by the FDA, cretostimogene may represent an important, bladder-sparing, advancement in the bladder cancer treatment paradigm, and meaningfully improve patient outcomes.”

BOND-003: Background and Design

The ongoing phase 3 BOND-003 study enrolled 115 adult patients with pathologically confirmed, high-risk, BCG-unresponsive NMIBC with carcinoma in situ, with or without resected high-grade Ta or T1 disease.³ Cohort C consists of a heavily pretreated population across academic and community sites in North America, Australia, and the Asia-Pacific region.

At the time of analysis, 112 patients received at least 1 dose of cretostimogene. The treatment regimen consists of intravesical cretostimogene (1 × 10¹² viral particles per 0·8 mL per week) as a 6-week induction followed by maintenance.

Secondary Outcomes: Bladder Preservation and Safety

Bladder preservation, a key secondary consideration for patients weighing intravesical therapy against radical cystectomy, was maintained in approximately 89% of patients at 12 months and 81% at 24 months. The rate of progression to muscle-invasive bladder cancer was low, with 96.6% of patients free from progression at both 48 and 96 weeks, corresponding to a 3.4% progression rate during the study period.

Regarding safety, no grade 3 or higher treatment-related adverse events, treatment-related discontinuations, or treatment-related deaths were reported. The most common treatment-related adverse events, occurring in at least 10% of patients, were bladder spasm, pollakiuria, micturition urgency, dysuria, and hematuria.

A Practical Option for the Outpatient Setting

The administration profile of cretostimogene may be relevant to community practices without ready access to procedural resources required by some existing bladder-sparing therapies. Because the regimen does not require prophylactic medication such as anticholinergics, operating room time, additional cystoscopy, or anesthesia dosing, delivery does not depend on procedural infrastructure typically associated with surgical or anesthesia-based interventions.

The investigators noted that the administration approach aligns with existing American Urology Association and Society of Urologic Nurses and Associates intravesical administration policy, which governs office-based delivery of intravesical agents. This alignment may support delivery of cretostimogene, if approved, in outpatient urology settings already equipped for existing intravesical treatments, without requiring additional procedural capacity.

Bladder Cancer Breakthrough: Understanding Cretostimogene

REFERENCES

1. CG Oncology Announces Publication of Pivotal Phase 3 BOND-003 Cohort C Study Results in The Lancet Oncology. News release. July 27, 2026. Accessed July 29, 2026. https://tinyurl.com/mxbt747x

2. Tyson M D, Nam JK, Joshi SS, et al. Intravesical cretostimogene grenadenorepvec oncolytic immunotherapy in high-risk, BCG-unresponsive, non-muscle-invasive bladder cancer with carcinoma in situ (BOND-003 Cohort C): a single-arm, phase 3 trial. Lancet Oncol. 2026;27(8):983-993. doi:10.1016/s1470-2045(26)00194-4

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 29, 2026. https://clinicaltrials.gov/study/NCT04452591