Experience With Cretostimogene Grenadenorepvec in NMIBC and Next Steps

Mark D. Tyson, II, MD, MPH, a urologic oncologist at Mayo Clinic in Phoenix, Arizona, concludes his conversation on the BOND-003 trial (NCT04452591) by discussing the next steps for research on cretostimogene grenadenorepvec.

BOND-003 is a phase 3 study evaluating cretostimogene grenadenorepvec for the treatment of patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). Updated findings from the study were presented at the 2024 American Urological Association (AUA) Annual Meeting.

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0:09 | In terms of the installation process itself, cretostimogene administration is a familiar and convenient workflow. It can be administered by nurses or medical assistants, and the favorable tolerability profile lends itself to high patient compliance. This is evidenced by the fact that no patient in the BOND-003 trial was unable to tolerate the installation and dwell.

0:37 | Recognizing that it's difficult to compare across studies due to underlying differences in the population, cretostimogene would at least appear to compare favorably to the current non surgical co standards of care. The 75% response rate observed for cretostimogene monotherapy compares favorably to the 62% observed for the N-803 combination therapy with BCG, to the 51% for nadofaragene, and to the 41% for pembrolizumab. Similarly, the duration of complete response for cretostimogene monotherapy compares favorably with 83% of responders at a 12-month time point having a duration of response greater than 12 months, vs 58% for N-803, and 46%, both for nadofaragene and pembrolizumab. Toxicity data compares favorably as well with no grade 3’s observed in BOND-003.

1:33 | Based upon the strength of these data, the FDA has granted CG Oncology fast track and breakthrough designations for the development of cretostimogene grenadenorepvec for the treatment of BCG-unresponsive non-muscle invasive bladder cancer. Two substantial amendments have been implemented. The first is a treatment extension phase for those who get to the end of the protocol in complete response. These patients can now get maintenance therapy on an every 6 month basis in years 2 and 3. And second is the addition of a papillary only cohort called cohort P. These patients have papillary only BCG-unresponsive non-muscle invasive bladder cancer and receive the same dosing schedule as cohort C. And we will be speaking more about cohort P design and implementation in the Learning Lab on Sunday at the AUA.

2:29 | I would also like to take this opportunity to announce on behalf of CG Oncology, the launch of the extended access and compassionate use program for cretostimogene. This program has a simplified inclusion exclusion criteria and is specifically designed to encompass geographical and ethnic diversity to offer real-world data across the spectrum of safety, efficacy, and patient experience, as well as patient-reported outcomes.

3:03 | It is also important to highlight the important collaboration between the SUO-CTC and CG Oncology. PIVOT-006, led by Robert Svatek, MD, is a phase 3 study evaluating cretostimogene vs observation alone for patients with BCG-naive intermediate-risk non-muscle invasive bladder cancer, and I am happy to report our first patients have already been dosed in that trial. On the horizon is CORE-008, a multi-arm, multi-cohort study evaluating cretostimogene in the treatment of BCG-naive and BCG-exposed high-risk non-muscle invasive bladder cancer.

3:40 | I would like to take this opportunity to thank the patients and their families, the study coordinators, and the nurses, as well as the key collaborators listed here. But especially Dr. Roger Li, MD, and Edward M. Uchio, MD, who were instrumental in the success of this trial. Thank you.