Intravesical treatment with the investigational immunotherapy cretostimogene grenadenorepvec (CG0070) 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 Mark D. Tyson, II, MD, MPH, of Mayo Clinic, Phoenix, 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].”
Mark D. Tyson, II, MD, MPH
As he 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, 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 the RB (retinoblastoma) 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.2
Study Design: Cohort P
Patients were aged at least 18 years with high-risk, papillary-only non–muscle-invasive bladder cancer that recurred within 6 months of their last adequate BCG dose and had undergone complete resection prior to study entry. Treatment with cretostimogene grenadenorepvec consisted of once-weekly intravesical instillations for 6 weeks (induction), followed by three weekly maintenance doses every 3 months during the first year, and every 6 months in years 2 and 3. The primary endpoint was high-grade event-free survival. Central pathology was utilized for disease assessment.
A total of 56 patients were enrolled in Cohort P, of whom 51 were evaluable for efficacy. The population was predominantly older (median age = 74.0 years), White (87.5%), and male (78.6%), with 96.4% enrolled from the United States. Nearly all patients (94%) 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).
High-Grade Recurrence-Free Survival Benefit
At a median follow-up of 6.0 months, cretostimogene grenadenorepvec demonstrated high-grade recurrence-free survival rates at 3, 6, and 9 months of 95.7%, 84.6%, and 80.4%, respectively. Eight patients were re-induced.
The high-grade recurrence-free survival benefit appeared to be consistent across both high-grade Ta and T1 disease. 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%. The rates were 100%, 100%, and 87.5%, respectively, for high-grade T1 disease.
“These results indicate that cretostimogene grenadenorepvec could significantly improve outcomes….”— MARK D. TYSON, II, MD, MPH
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Importantly, said Dr. Tyson, no patients underwent radical cystectomy during the follow-up period, and none 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” and similar to that seen in prior cohorts, Dr. Tyson noted. Most adverse events were grade 1 or 2. There were no grade 3 treatment-related adverse events, serious treatment-related adverse events, treatment-related discontinuations, or deaths.
A total of 98.2% of the cohort received all protocol-defined instillations. Common treatment-related adverse events (> 10%) 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
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 patients with papillary-only disease, Dr. Tyson stressed that randomized controlled trials are “on the horizon.”
“They’re needed,” he 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 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. 2025 SUO Annual Meeting. Presented December 5, 2025.
2. Tyson MD, Uchio EM, Nam J-K, et al: Final results: BOND-003 Cohort C- Phase 3, single-arm study of intravesical cretostimogene grenadenorepvec for high-risk BCG-unresponsive non-muscle invasive bladder cancer with carcinoma in situ. J Urol 213:e1, 2025.
