Cretostimogene Grenadenorepvec Yields Sustained Antitumor Activity in NMIBC

Phase 3 BOND-003 trial results revealed that 75% of patients treated with cretostimogene grenadenorepvec monotherapy achieved a complete response at any point during the study period.

Data from cohort C of the phase 3 BOND-003 trial showed cretostimogene grenadenorepvec elicited sustained antitumor activity in patients with Bacillus-Calmette-Guerin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), according to a news release from the drug’s developer, CG Oncology.¹

Findings from the trial were presented at the 40th Annual European Association of Urology (EAU) Congress and revealed that of 110 patients treated with cretostimogene grenadenorepvec monotherapy, 83 (75.5%) achieved a complete response (CR) at any point during the study period. Additionally, as of the data cut-off date of January 20, 2025, the median duration of response (DOR) had not been reached and exceeded 28 months. Furthermore, the 12-month CR rate was 46%, and 30 patients had confirmed CRs at 24 months.

“Cretostimogene’s strong safety and efficacy profile, combined with its best-in-class durability, address an unmet need for my [patients with] NMIBC,” Trinity J. Bivalacqua, MD, professor of Urology and Oncology at the Perelman Center for Advanced Medicine, University of Pennsylvania, said in the news release.¹ “Now with the new translational data indicating that post-treatment close contact precautions are unnecessary, I am confident that cretostimogene will represent a breakthrough in bladder cancer treatment if approved by the FDA.”

Cohort C of the phase 3 BOND-003 trial enrolled patients with NMBIC with carcinoma in situ who progressed following prior BCG therapy to receive cretostimogene grenadenorepvec monotherapy. Prior to cretostimogene grenadenorepvec dosing, patients underwent a series of bladder washes with 5% DDM and saline.²

Cretostimogene was given 6 times weekly for 6 weeks. If disease recurrence was reported at week 13, they were given an additional cycle of 6 weekly treatments. Additionally, if disease recurrence was noted at week 13, they were given another cycle of 6 weekly treatment, however, if it was not observed, weekly dosing was reduced to 3 treatments.

Starting at week 25, patients received 3 treatments every 12 weeks up to week 51, followed by every 6 months. Final treatment occurred weeks 73, 74, and 75 until tumor recurrence or study completion at 97 weeks. In an expansion cohort, at week 25, patients received 3 treatments every 12 weeks through week 51, and then starting weeks 73, 74, and 75, every 6 months until weeks 157, 158, and 159 until tumor recurrence or study completion at 159 weeks.

The primary end point of cohort C was CR rate in those with BCG-unresponsive CIS. Secondary end points in this cohort included DOR, recurrence-free survival, progression-free survival, overall survival, and safety of cretostimogene grenadenorepvec.

According to translational data presented at the EAU Congress, cretostimogene levels peaked immediately after instillation and were sustained locally for 4 to 5 days. Its intravesical delivery reduced anti-drug body neutralization, preserving efficacy. Close contact precautions were not needed, given there was no systemic exposure to cretostimogene.

No grade 3 or greater treatment-related adverse effects (TRAEs) or deaths were reported on study. TRAEs occurring in 10% of patients or greater included bladder spasm, pollakiuria, micturition urgency, dysuria, and hematuria. A median resolution time of 1 day was observed among those who experienced a TRAE. A total of 97.3% of patients completed treatment and no treatment-related discontinuations were observed.

“We are highly encouraged by the latest [phase 3] BOND-003 results, the largest study to date in [patients with] BCG-unresponsive NMIBC with CIS, and cretostimogene’s potential to significantly impact the future of bladder cancer care,” Ambaw Bellete, president and chief operating officer of CG Oncology, said in the news release.¹ “We are grateful to the patients and providers who participated in our study, advancing research and offering hope to those seeking bladder-sparing options.”

References

1. Cretostimogene grenadenorepvec data continues to demonstrate best-in-class durability of response as well as consistent and compelling safety and efficacy. News release. CG Oncology. March 24, 2025. Accessed March 25, 2025. https://tinyurl.com/3vvcux2b
2. Study of cretostimogene given in patients with non-muscle invasive bladder cancer, unresponsive to Bacillus-Calmette-Guerin (BOND-003). ClinicalTrials.gov. Updated January 6, 2025. Accessed March 25, 2025. https://tinyurl.com/haurf76v