Published BOND-003 data show durable responses with cretostimogene in NMIBC

Data from Cohort C of the pivotal phase 3 BOND-003 trial (NCT04452591) have been published in Lancet Oncology, showing that intravesical cretostimogene grenadenorepvec led to high complete response (CR) rates with a favorable safety profile in patients with high-risk, BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without concomitant Ta/T1 disease.¹

The results showed a CR rate of 75% at any time and a median duration of response approaching 28 months in a heavily pretreated patient population.

“Patients with BCG-unresponsive NMIBC often face the difficult decision between pursuing additional bladder-sparing therapies or undergoing a severe, life-altering cystectomy,” said lead author Mark D. Tyson II, MD, MPH, of Mayo Clinic, in a news release on the results.² “The results from BOND-003 represent a potential shift in this treatment paradigm, underpinned by encouraging durability of response and bladder preservation outcomes. With a clinically meaningful median duration of response of 27.9 months, possibly among the longer duration of responses seen in this setting, 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.”

How is the BOND-003 trial designed?

BOND-003 Cohort C is an ongoing international, single-arm phase 3 trial conducted across 41 academic and community sites in North America, Asia, and Australia. Investigators enrolled adults with pathologically confirmed high-risk, BCG-unresponsive NMIBC with CIS, with or without resected high-grade Ta or T1 disease. The median age was 74 years. Patients were heavily pretreated, with a median of 12 (IQR, 9 to 15) previous intravesical BCG instillations.

Patients received intravesical cretostimogene grenadenorepvec once weekly for 6 weeks followed by maintenance therapy, with reinduction permitted for persistent disease at 3 months. Among 115 enrolled patients, 112 received at least 1 dose of treatment and 110 were evaluable for efficacy. Median follow-up at the June 23, 2025, data cutoff was 25.8 months.

What were the key efficacy and safety results from BOND-003?

The trial met its primary end point, with investigators reporting a centrally confirmed CR at any time in 83 of 110 patients (75%; 95% CI, 66.3 to 83.2). The authors noted that this CR rate is significantly greater than the historical benchmark. CR rates observed across subgroup analyses were generally consistent with the overall CR at any time.

Among responders, the estimated probability of remaining disease free was 64.2% at 12 months and 60.1% at 24 months, with an estimated median duration of response of 27.9 months. One patient remained disease free beyond 51 months after completing maintenance therapy.

Kaplan-Meier estimates showed cystectomy-free survival rates of 89% at 12 months and 81% at 24 months. Disease progression to muscle-invasive bladder cancer occurred in 4 patients, while overall stage progression was observed in 13 patients (12%). Among 18 patients who ultimately underwent radical cystectomy after recurrence or progression, 15 (83%) had non–muscle-invasive disease or pathologic T0 disease on final pathology.

Treatment was generally well tolerated. Treatment-related adverse events occurred in 63% of patients and were predominantly grade 1 or 2 lower urinary tract symptoms, including bladder spasm, pollakiuria, urinary urgency, dysuria, and hematuria. Investigators reported no grade 3 or 4 treatment-related adverse events and no treatment-related deaths. The median time to resolution of treatment-related adverse events was 1 day. Two grade 2 serious treatment-related adverse events—noninfective cystitis and urinary bladder hemorrhage—were reported.

Tyson added, “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. If approved by the FDA, cretostimogene may represent an important, bladder-sparing, advancement in the bladder cancer treatment paradigm, and meaningfully improve patient outcomes.”

Cretostimogene grenadenorepvec is an investigational intravesical oncolytic immunotherapy designed to selectively replicate in tumor cells with retinoblastoma-E2F pathway abnormalities and amplifying an antitumor immune responses. The agent has received FDA Fast Track and Breakthrough Therapy designations for BCG-unresponsive high-risk NMIBC with CIS but has not been approved by the agency.

The BOND-003 trial remains ongoing, with additional analyses planned to inform the durability of response to cretostimogene. Additional studies such as PIVOT-006 (NCT06111235) and CORE-008 (NCT06567743) are also assessing the agent’s role across the bladder cancer landscape.

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