Intravesical cretostimogene grenadenorepvec (CG0070) monotherapy demonstrated strong high-grade recurrence-free survival rates in patients with high-risk, papillary-only, bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer, according to data presented at the 26th Annual Meeting of the Society of Urologic Oncology (SUO).¹

Topline results from Cohort P of the multinational, single-arm phase III BOND-003 study showed a 95.7% 3-month, 84.6% 6-month, and 80.4% 9-month high-grade recurrence-free survival rate for patients who received the bladder-sparing treatment option.

“The single-arm BOND-003 study showed compelling efficacy and excellent tolerability,” said lead study author Mark D. Tyson, II, MD, MPH, of Mayo Clinic in Arizona, who presented the findings. “These results indicate that cretostimogene grenadenorepvec could significantly improve outcomes for papillary-only disease in BCG-unresponsive [non–muscle-invasive bladder cancer].”

As Dr. Tyson explained, high-risk papillary-only (HG Ta/T1) non–muscle-invasive bladder cancer represents a significant unmet medical need. Current agents approved by the U.S. Food and Drug Administration (FDA) in this space are predominantly for carcinoma in situ disease, leaving a gap for patients with papillary-only tumors whose disease recurs within 6 months of adequate BCG.

“Radical cystectomy remains the standard of care for many, but is a formidable surgery,” said Dr. Tyson, who noted that recent meta-analyses have reported benchmarks for high-grade recurrence-free survival in this population of 73% at 3 months, 58% at 6 months, and 48% at 12 months—highlighting an opportunity for improved durability.

Cretostimogene grenadenorepvec is a conditionally replicating oncolytic adenovirus with a dual mechanism of action: it selectively replicates in cancer cells with RB pathway dysfunction, causing direct tumor cell lysis, and it expresses granulocyte-macrophage colony-stimulating factor to stimulate dendritic cell activation and prime tumor-specific immunity. This has previously demonstrated excellent durability in BCG-unresponsive carcinoma in situ, achieving a 75.5% complete response rate in Cohort C, with a favorable safety profile.

BOND-003 Cohort P Study Design

The BOND-003 Cohort P study was a single-arm, open-label trial specifically designed for patients with high-risk, papillary-only (HG Ta/T1) non–muscle-invasive bladder cancer whose disease recurred within 6 months of their last adequate BCG dose. Patients were aged ≥ 18 years and had their disease completely resected prior to study entry. Treatment consisted of once-weekly instillations for 6 weeks for induction, followed by 3 weekly maintenance doses every 3 months for the first year, and then every 6 months in years 2 and 3. The primary endpoint was high-grade event-free survival. Central pathology was utilized for disease assessment.

Fifty-six patients were enrolled in Cohort P, 51 of whom were efficacy-evaluable. The patient demographics were predominantly older (median age = 74.0 years), White (87.5%), and male (78.6%), with 96.4% enrolled from the United States. Ninety-four percent had an Eastern Cooperative Oncology Group performance status of 0. The population was high-risk, with 58.9% having high-grade Ta disease and 41.1% having high-grade T1 disease at study entry. The median number of prior BCG instillations was nine (range = 5–21).

Strong High-Grade Recurrence-Free Survival Rates

At a median follow-up of 6.0 months (data cutoff of September 1, 2025), cretostimogene grenadenorepvec demonstrated strong high-grade recurrence-free survival rates, with 3-month, 6-month, and 9-month rates of 95.7%, 84.6%, and 80.4%, respectively. Eight patients were re-induced.

The high-grade recurrence-free survival benefit was consistent across both high-grade Ta and high-risk T1 subsets. For high-grade Ta disease, the 3-month rate was 92.8%, the 6-month rate was 75.9%, and the 9-month rate was 75.9%. For high-grade T1 disease, the 3-month rate was 100%, the 6-month rate was 100%, and the 9-month rate was 87.5%.

Importantly, said Dr. Tyson, no patients underwent radical cystectomy during the follow-up period, and no patients progressed to muscle-invasive bladder cancer (one patient progressed to metastatic urothelial carcinoma despite clinical complete response in the bladder).

The tolerability profile was excellent, similar to prior cohorts. Most adverse events were grade 1 or 2. There were no grade 3 treatment-related adverse events, no serious treatment-related adverse events, no treatment-related discontinuations, and no deaths.

Ninety-eight percent (98.2%) of the cohort received all protocol-defined instillations. Common treatment-related adverse events (reported in > 10% of patients) included bladder spasm (46.4%), dysuria (39.3%), pollakiuria (25.0%), and urgency (19.6%), all of which were grade 1 or 2.

“The topline results from BOND-003 Cohort P demonstrate that [cretostimogene grenadenorepvec] monotherapy provides strong and consistent high-grade recurrence-free survival rates at 3, 6, and 9 months in high-risk, papillary-only, BCG-unresponsive [non–muscle-invasive bladder cancer], even in the highest-risk T1 subset,” said Dr. Tyson. “The excellent tolerability profile, with no grade 3 treatment-related adverse events or progression to muscle-invasive bladder cancer, underscores its potential as a valuable bladder-sparing option.”

Future Directions in Papillary-Only Non–Muscle-Invasive Bladder Cancer

According to Dr. Tyson, longer-term follow-up is ongoing. The rolling Biologics License Application (BLA) for cretostimogene grenadenorepvec has been submitted to the FDA, with a decision anticipated next year.

Addressing the future implications of these and similar findings for papillary-only patients, Dr. Tyson stressed that randomized controlled trials are “on the horizon.”

“They’re needed,” Dr. Tyson added. “While these single-arm studies provide valuable prospective data, ultimately, randomized controlled trials are … needed for us to accurately estimate the average treatment effects of these new therapies.”

Disclosure: Dr. Tyson reported no potential conflicts of interest.

References

1. Tyson M: Topline results from BOND-003 Cohort P-A multi-national, single-arm study of intravesical cretostimogene grenadenorepvec for treatment of high-risk, papillary only (HG Ta/T1), BCG-unresponsive NMIBC. 26th Annual Meeting of the Society of Urologic Oncology. Presented December 5, 2025.