CORE-008: Cretostimogene achieves high CR rate in high-risk NMIBC

Cretostimogene grenadorepvec monotherapy for patients with high-risk BCG-naïve non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) yielded high complete response (CR) rates and strong safety outcomes, according to the first reported data from the phase 2 CORE-008 (NCT06567743) trial presented at the 2025 Society of Urologic Oncology (SUO) Annual Meeting in Phoenix, Arizona.¹

“As this room is very aware, there are challenges with the utilization of BCG, especially here in America, as well as around the world. We know that BCG is effective…There is an ongoing shortage, which hopefully we'll be able to address in the near future. But the meantime, we need to be considering additional intravesical agents for patients with high-risk, non–muscle invasive bladder cancer that have not been exposed to BCG,” explained Trinity J. Bivalacqua, MD, PhD, director of urologic oncology, co-director of the Genitourinary Cancer Service Line, Abramson Cancer Center, and a professor of surgery at the Hospital of the University of Pennsylvania in Philadelphia during his presentation.

Patients in the phase 2, multi-cohort CORE-008 trial were required to have had no prior BCG, BCG longer than 24 months prior, or a maximum of 1 to 2 doses of BCG within the past 24 months of their current diagnosis. At SUO 2025, Bivalacqua specifically outlined data for patients with carcinoma in situ only (cohort A). In all study cohorts, a weekly induction course was given for the first 6 weeks. Re-induction was administered if patients had CIS and/or high-grade Ta disease at 3 months. After the induction phase, patients in whom no high-grade disease was detected began maintenance treatment, comprising 3 weekly treatments every 3 months for year 1, and every 6 months for year 2. An extension for year 3 with the 6-month schedule was optional.²

Cystoscopy and cytology were preformed every 3 months, and mandatory mapping biopsies were conducted at 12 months. Patients received a CT/MRU every 6 months.

Of the 54-patient cohort, 49 (90.7%) were male and 5 (9.3%) were female. Mean age was 73.2 years (standard deviation [SD], 8.84), and median age was 73.5 years (range, 69-79 years). Most patients (92.6%) were White and over 65 years of age (88.8%). ECOG performance status was 0 in 44 (81.5%) patients and 1 in 10 (18.5%) patients. At study entry, 24 (44.4%) patients had CIS alone, 17 (31.5%) had CIS with high-grade Ta disease, and 13 (24.1%) had CIS with high-grade T1 disease. Forty-seven (87.0%) had not received prior BCG, and 7 (13.0%) had received BCG longer than 24 months prior. Seven (13.0%) patients had received adjuvant IVE chemotherapy, and 47 (87.0%) had not.

The cohort continued to be well balanced when stratified by the study’s original administration approach (5-step instillation with series of bladder saline washes followed by DDM and cretostimogene instillations) compared with optimized administration (a 2-step process with DDM followed by cretostimogene instillations).

A total of 49 patients underwent efficacy assessment at the time of data cut-off. Overall CR rate was 83.7% (95% CI, 70.3-92.7). Broken out by administration approach, the CR rate with the original approach was 79.2% (95% CI, 57.8-92.9); for the optimized approach, the CR rate was 88.0% (95% CI, 68.8-97.5).

Median follow-up was 4.6 months. None of the patients in the cohort required radical cystectomy, and no treatment-related progression to muscle-invasive bladder cancer or metastatic urothelial carcinoma. Three patients had reclassification of their NMIBC stage.

The treatment was found to be well tolerated. There were no grade 3 or higher treatment-related adverse events (AEs), serious AEs, or deaths. No treatment-related discontinuations were observed, and all but 1 patient completed all protocol-defined treatments. Treatment-emergent AEs occurring in more than 10% of patients included bladder spasm, dysuria, pollakiuria, hematuria, and fatigue.

“Cretostimogene monotherapy has consistent efficacy and safety and tolerability in BCG-naïve, non–muscle-invasive bladder cancer with CIS. It aligns well with our urology workflow and intravesical treatment…These findings support additional development of cretostimogene in multiple disease spaces,” Bivalacqua said in his concluding remarks.

“We are delighted to share new and more mature data in different sub-groups, underscoring our commitment to address the broadest range of NMIBC patients. This sets us up for the future expansion and long-term success of cretostimogene. With its best-in-disease profile and dual MOA, we are confident that cretostimogene will continue to demonstrate differentiated data from current and investigational NMIBC therapies,” said Ambaw Bellete, President and Chief Operating Officer at CG Oncology, in a news release from the company.³

REFERENCES

1. Bivalacqua T. First results from CORE-008 Cohort A- Phase 2 study of intravesical cretostimogene grenadenorepvec in patients with high-risk BCG-naïve non-muscle invasive bladder cancer. Presented at: Society of Urologic Oncology Annual Meeting; December 2-5, 2025; Phoenix, Arizona. Late-breaking abstract

2. Phase 2 Study to Evaluate Safety and Efficacy of Cretostimogene Grenadenorepvec in High-Risk NMIBC. ClinicalTrials.gov. Updated October 8, 2025. Accessed December 5, 2025. https://clinicaltrials.gov/study/NCT06567743

3. New cretostimogene grenadenorepvec data highlight its potential to become the backbone therapy for high-risk non-muscle invasive bladder cancer. News release. CG Oncology. December 5, 2025. Accessed December 5, 2025. https://ir.cgoncology.com/news-releases/news-release-details/new-cretostimogene-grenadenorepvec-data-highlight-its-potential