Study launches of cretostimogene grenadenorepvec in NMIBC

The first patient has been dosed in the phase 3 PIVOT-006 trial (NCT06111235) exploring the efficacy of cretostimogene grenadenorepvec (CG0070) following transurethral resection of the bladder tumor (TURBT) in patients with intermediate-risk non–muscle-invasive bladder cancer (NMIBC), announced CG Oncology, the developer of cretostimogene, in a news release.¹

Primary completion of the PIVOT-006 trial is expected in 2028.

“The dosing of the first patient in our PIVOT-006 trial advances cretostimogene earlier in the treatment paradigm for NMIBC patients who face limited treatment options, frequent disease recurrence, and repetitive surgery,” said Arthur Kuan, chairman and CEO of CG Oncology, in the news release.¹ “Intermediate-risk NMIBC patients face a difficult combination of disease characterized by tumor recurrence and a shortage of BCG therapy which is often reserved for use only in high-risk patients, limiting treatment options for intermediate-risk patients. Our goal with the PIVOT-006 trial is to advance cretostimogene as a potential backbone oncolytic immunotherapy.”

Overall, the open-label PIVOT-006 trial plans to enroll 426 patients with intermediate-risk NMIBC across clinical trial sites in the US and Canada. Patients will be randomly assigned 1:1 to receive cretostimogene following standard-of-care TURBT or observation following TURBT alone.

Those included in the investigational arm will receive 1x1012 VPs per milliliter cretostimogene given in 6 weekly doses for the initial induction course. Patients who remain recurrence-free at 3-month follow-up will receive a maintenance course consisting of 3 weekly doses of cretostimogene at the same dose level in months 3 and 6, followed by single weekly doses in months 9 and 12.

Inclusion criteria for the study includes having pathologically confirmed intermediate-risk NMIBC, removal of all visible disease by TURBT, and acceptable baseline organ function. Patients are excluded from the study if they present with low- or high-risk NMIBC, contain disease in the prostatic urethra, have muscle-invasive bladder cancer (MIBC) or locally advanced or metastatic bladder cancer, or have received prior treatment with any human adenovirus serotype 5 based therapy.²

The primary end point for the PIVOT-006 study is the overall recurrence-free survival (RFS). Secondary end points for the study include RFS at 12 months and 24 months, as well as progression-free survival and the incidence of adverse events.

“I am excited to see the PIVOT-006 study get underway in the intermediate-risk NMIBC population with cretostimogene, a highly selective oncolytic immunotherapy. Novel treatment options and clinical trials are essential in NMIBC, particularly in this group of underserved patients who undergo considerable follow up and have limited intravesical therapeutic options. Cretostimogene is a novel therapy which has the potential to be a paradigm shift in how we might manage the ongoing burden of this highly recurrent aspect of bladder cancer,” said Neal D. Shore, MD, FACS, in the news release.¹ Shore is the medical director for the Carolina Urologic Research Center in Myrtle Beach, South Carolina.

Primary completion of the PIVOT-006 trial is expected in 2028.

In addition to the PIVOT-006 trial, cretostimogene is also being explored in the phase 3 BOND-003 trial (NCT04452591) in patients with BCG-unresponsive NMIBC, as well as in the phase 2 CORE-001 (NCT04387461) trial in combination with pembrolizumab for the same indication. An investigator-initiated trial is also assessing the therapy in combination with nivolumab for the treatment of patients with MIBC. Further, the phase 2 CORE-008 study is planned to assess cretostimogene in patients with high-risk, BCG-naïve and BCG-exposed NMIBC.³

Reference

1. CG Oncology announces first patient dosed in PIVOT-006 phase 3 clinical trial of cretostimogene in intermediate-risk non-muscle invasive bladder cancer. News release. CG Oncology. February 27, 2024. Accessed February 29, 2024. https://ir.cgoncology.com/news-releases/news-release-details/cg-oncology-announces-first-patient-dosed-pivot-006-phase-3-0

2. A study of adjuvant cretostimogene grenadenorepvec for treatment of intermediate risk NMIBC following TURBT. ClinicalTrials.gov. Last updated December 20, 2023. Accessed February 29, 2024. https://www.clinicaltrials.gov/study/NCT06111235

3. Cretostimogene grenadenorepvec clinical studies. CG Oncology, Inc. Accessed February 29, 2024. https://cgoncology.com/pipeline/