Enrollment goal met in PIVOT-006 trial of cretostimogene grenadenorepvec in IR-NMIBC

The target enrollment has been reached in the phase 3 PIVOT-006 trial (NCT06111235), which is comparing outcomes with adjuvant intravesical cretostimogene grenadenorepvec vs surveillance following transurethral resection of bladder tumor (TURBT) in patients with intermediate-risk non–muscle invasive bladder cancer (IR-NMIBC), CG Oncology reported in a news release.¹

Cretostimogene is an investigational, intravesically delivered oncolytic adenovirus. The agent was granted breakthrough therapy and fast track designations by the FDA in December 2023.

“Intermediate-risk NMIBC presents a significant clinical challenge, with recurrence rates reaching up to 70% and few durable treatment options available to patients. Although it carries a lower risk of progression than high-risk disease, the relentless cycle of procedures and surveillance can diminish patients’ quality of life,” explained global principal investigator Robert S. Svatek, MD, MSCI, urologic oncologist at the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, in the news release.¹ “There is growing enthusiasm within the urology community about the potential of cretostimogene in both intermediate- and high-risk NMIBC, underscored by the rapid enrollment of over 360 patients into the PIVOT-006 study across 90 plus sites. This unique therapy introduces a novel treatment paradigm—selectively lysing tumor cells while simultaneously activating a robust anti-cancer immune response.”

Patients were enrolled in the open-label study through clinical trial sites across the US and Canada.² To be eligible for enrollment, patients needed to have pathologically confirmed IR-NMIBC, acceptable baseline organ function, and all visible disease removed by TURBT within 90 days of study randomization.

Patients enrolled in the trial will undergo standard TURBT and will then be randomly assigned 1:1 to receive adjuvant intravesical cretostimogene or undergo surveillance. Cretostimogene instillations will be administered weekly for 6 weeks, followed by weekly instillations for 3 weeks every 3 months for 1 year. Patients in the surveillance arm may cross over to the treatment arm if they experience disease recurrence.

The primary end point for the trial is recurrence-free survival (RFS), as assessed through 51 months. Secondary end points include RFS at 12 months and 24 months as well as the incidence of adverse events (AEs).

Primary completion of the trial is expected in January 2028.

Cretostimogene Trial Platform

In addition to PIVOT-006, cretostimogene is being explored in 2 other additional studies: the phase 2 CORE-008 trial (NCT06567743) and the phase 3 BOND-003 trial (NCT04452591). CORE-008 is a phase 2 study evaluating the safety and efficacy of cretostimogene in patients with high-risk NMIBC.³ BOND-003 is assessing cretostimogene in patients with high-risk NMIBC who have failed prior BCG therapy.⁴

Updated data from the BOND-003 trial were presented at the 2025 American Urological Association Annual Meeting in Las Vegas, Nevada.⁵ Overall, data from cohort C in the study showed that treatment with cretostimogene yielded an overall complete response (CR) rate of 75.5% (95% CI, 66.3% to 83.2%) in patients with high-risk, BCG-unresponsive NMIBC with carcinoma in situ plus or minus high-grade Ta/T1 disease. At the time of data cutoff, 46.4% of patients remained in CR at a year, and 33.7% of the cohort was in response at 2 years.

Treatment was also well-tolerated, with AEs generally being grade 1 or 2, according to the authors.

Both the BOND-003 trial and the CORE-008 trial are expecting to reach primary completion in 2027.

“At CG Oncology, we remain steadfast in our mission to transform the treatment landscape for individuals living with bladder cancer,” concluded Vijay Kasturi, MD, Chief Medical Officer at CG Oncology, in the news release. “Our clinical trial program is purposefully designed to address the full spectrum of disease stages and tumor types, with a particular focus on areas of high unmet need. We are especially encouraged by the strong interest and rapid enrollment, nearly a year ahead of schedule, in PIVOT-006 which highlights the urgent need for new treatment options in the intermediate-risk NMIBC population. This momentum reinforces our path toward a potential indication in adjuvant IR NMIBC, for which there are no U.S. FDA approved options. We are deeply grateful to the SUO-CTC for their support, to all participating trial sites for their dedication, and most importantly, to the patients who make this research possible.”

REFERENCES

1. CG Oncology completes enrollment in PIVOT-006. News release. CG Oncology, Inc. September 3, 2025. Accessed September 3, 2025. https://ir.cgoncology.com/news-releases/news-release-details/cg-oncology-completes-enrollment-pivot-006

2. A study of adjuvant cretostimogene grenadenorepvec for treatment of intermediate risk NMIBC following TURBT. ClinicalTrials.gov. Last updated July 30, 2025. Accessed September 3, 2025. https://www.clinicaltrials.gov/study/NCT06111235

3. Phase 2 study to evaluate safety and efficacy of cretostimogene grenadenorepvec in high-risk NMIBC. ClinicalTrials.gov. Last updated July 17, 2025. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT06567743

4. Study of cretostimogene given in patients with non-muscle invasive bladder cancer ,unresponsive to bacillus-calmette-guerin (BOND-003). ClinicalTrials.gov. Last updated July 3, 2025. Accessed September 3, 2025. https://clinicaltrials.gov/study/NCT04452591

5. 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. 2025;213(5S)