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Intravesical cretostimogene grenadenorepvec was efficacious and safe in high-risk BCG-naive non–muscle-invasive bladder cancer.
Intravesical cretostimogene grenadenorepvec displayed efficacy and safety in patients with high-risk BCG-naive non–muscle-invasive bladder cancer (NMIBC), according to data from cohort A of the phase 2 CORE-008 trial (NCT06567743) presented during the 26th Annual Meeting of the Society of Urologic Oncology.1
At a median follow-up of 4.6 months, efficacy-evaluable patients who received intravesical cretostimogene grenadenorepvec (n = 49) achieved a complete response (CR) rate of 83.7% (95% CI, 70.3%-92.7%). No patients required radical cystectomy and there were no instances of treatment-related progression to MIBC or urothelial carcinoma. Of note, 3 patients did require NMIBC stage reclassification
“Cretostimogene monotherapy has [demonstrated] consistent efficacy and safety and tolerability in BCG-naive NMIBC with carcinoma-in-situ [CIS],” Trinity J. Bivalacqua, MD, PhD, the director of Urologic Oncology and the codirector of the Genitourinary Cancer Service Line at the Abramson Cancer Center, as well as a professor of surgery at the Hospital of the University of Pennsylvania, both in Philadelphia, said during the presentation. “[Intravesical treatment] aligns well with our urology workflow [and] the optimized administration appears to be equally as effective and tolerable as that of the 5-step [administration].”
In the open-label CORE-008 study, 125 patients with pathologically confirmed, high-risk, high-grade, BCG-naive NMIBC were enrolled onto cohort A.1,2 Other key inclusion criteria included having all visible disease resected, all carcinoma-in-situ (CIS) resected or fulgurated as feasible within 90 days prior to treatment allocation, and adequate organ function. BCG-naive disease was defined as having not received prior BCG, BCG more than 24 months before enrollment, or a maximum of 1 to 2 doses within the past 24 months of current diagnosis.1
In cohort A, patients were randomly assigned 1:1 to the original 5-step protocol or an optimized 2-step administration approach. Re-induction was permitted for patients with high-grade Ta disease and/or CIS at month 3. Cystoscopy and cytology were performed every 3 months with mandatory mapping biopsies at 12 months. CT/MRU were performed every 6 months, and treatment was optional in year 3.
The primary end points in cohort A were CR rate and high-grade event-free survival.2 Secondary end points included evaluating cretostimogene genome and GM-CSF levels, treatment efficacy, and safety by 2 different methods of cretostimogene instillation; determining the proportion of participants with BCG-naive papillary-only high-grade NMIBC at baseline who are free from high-grade events at 12 months; and assessing the duration of response in patients with CIS with or without concomitant high-grade Ta/T1 disease at baseline.
At baseline, the median age in cohort A (n = 54) was 73.5 years (range, 60-79).1 Most patients were male (90.7%), White (92.6%), older than 65 years of age (88.8%), had an ECOG performance status of 0 (81.5%), and had not received prior BCG (87.0%). All patients were enrolled in the United States.
Intravesical cretostimogene grenadenorepvec produced high CR rates across prespecified patient subgroups. Specifically, the CR rates among patients who were younger than 65 years of age (n = 6), had an ECOG performance status of 1 at baseline (n = 10), and who received the agent via the optimized administration method (n = 27) were 100% (95% CI, 54.1%-100%), 100% (95% CI, 69.2%-100%), and 88.0% (95% CI, 68.8%-97.5%), respectively.
In terms of safety, any-grade treatment-related adverse effects (TRAEs) occurred in 53.7% of patients and included bladder spasm (24.1%), dysuria (20.4%), pollakiuria (14.8%), hematuria (14.8%), and fatigue (14.8%). There were no serious adverse effects or grade 3 or higher TRAEs. No treatment-related discontinuations were reported. Most patients across both administration methods completed treatment (98.1%).
“These findings support additional development of cretostimogene in multiple disease spaces,” Bivalacqua concluded.
Disclosures: Bivalacqua received grants from NIH SBIR, DOD, RO1, and the AUA Care Foundation. He received clinical trial support from CG Oncology and Ferring Pharmaceuticals. He is on the scientific advisory boards of Urogen, CG Oncology, and Pfizer. He is the cofounder of OncoSTING LLC.
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