Cretostimogene demonstrates safety, efficacy in papillary NMIBC cohort

Data from the phase 3 BOND-003 trial (NCT04452591) evaluating the investigational oncolytic immunotherapy cretostimogene grenadenorepvec in patients with high-risk, papillary only, BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) indicate the treatment is safe and efficacious in this treatment population.¹

The results were presented as a late-breaking abstract at the 2025 Society of Urologic Oncology Annual Meeting in Phoenix, Arizona.

“Every FDA-approved agent in this space is approved for CIS only. None are approved for Ta or T1 disease, the so-called ‘papillary-only’ subset, despite this being a population that we see frequently in practice. A recent meta-analysis provided some very helpful high-grade, recurrence-free survival benchmarks for this population. Seventy-three percent are disease free at 3 months, and 58% and 48% are disease free at 6 and 12 months, respectively, so clearly some opportunity with respect to durability,”² explained Mark D. Tyson II, MD, MPH, a urologic oncologist with Mayo Clinic in Phoenix, Arizona during his presentation.

Tyson briefly summarized data from cohort C of BOND-003, which evaluated cretostimogene in patients with high-grade, BCG-unresponsive NMIBC with CIS +/– Ta/T1 disease. In that group of patients, the overall CR rate was 75.5% (95% CI, 66.3-83.2). Additionally, 96.4% of patients were free from progression to muscle-invasive bladder cancer, and 83.6% of patients did not receive radical cystectomy post recurrence or progression. No grade 3 or higher treatment-related adverse events were reported, no deaths occurred, and no treatment-related discontinuations were reported.

Cohort P included adult patients with pathologically confirmed high-risk, BCG-unresponsive high-grade Ta/T1 NMIBC (no CIS) that was completely resected prior to treatment with cretostimogene. The primary end point was high-grade event-free survival (EFS); secondary end points included recurrence-free survival, progression-free survival, cystectomy-free survival, and cancer-specific survival.

Forty-four (78.6%) patients were male, and 12 (21.4%) were female. Mean age was 71.6 years (standard deviation, 9.3), and median age was 74.0 years (range, 45-87 years). ECOG performance status was 0 in 48 (85.7%) patients and 1 in 8 (14.3%) patients.

Thirty-three (58.9%) patients had high-grade Ta disease at study entry, and 23 (41.1%) had high-grade T1 disease. Median number of prior BCG instillations was 9.0 (range, 5-21 instillations).

Median follow-up was 8 months. Eight patients underwent re-induction of cretostimogene. In patients with high-grade Ta disease, high-grade EFS was 92.8% at 3 months, 75.9% at 6 months, and 75.9% at 9 months. In patients with high-grade T1 disease, high-grade EFS was 100% and 3 months and at 6 months and 87.5% at 9 months. None of the patients received a radical cystectomy, and none progressed to muscle-invasive bladder cancer.

Regarding safety, “Similar to cohort C, tolerability was excellent in cohort P,” Tyson reported. Most AEs were grade 1 or 2, and there were no grade 3 or higher AEs, serious treatment-related AEs, or deaths. Forty (71.4%) patients had at least 1 treatment-related AE. Treatment-related AEs that occurred in more than 10% of the cohort included bladder spasm, dysuria, pollakiuria, and urgency. No treatment-related discontinuations occurred, and 98.2% of the cohort received all protocol-defined treatments.

“In conclusion, top-line results from cretostimogene in BOND-003 cohort P looked very promising. We see strong high-grade [event]-free survival rates at 3, 6, and 9 months, even in the highest risk subset, which is the T1 population. We see consistent and favorable tolerability as well,” Tyson said.

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, BCG-unresponsive non-muscle invasive bladder cancer. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Late-breaking abstract

2. Rose KM, Garcia-Perdomo H, Bivalacqua TJ, et al. Systematic review and meta-analysis of response rates in BCG-unresponsive non–muscle-invasive bladder cancer: A consensus statement from the International Bladder Cancer Group. Soc. Int. Urol. J. 2022;3(5):333-339. doi:10.48083/CKYL2827