FDA grants cretostimogene grenadenorepvec Breakthrough and Fast Track Designations for NMIBC

The FDA has granted the oncolytic immunotherapy cretostimogene grenadenorepvec Breakthrough Therapy and Fast Track Designations for the treatment of patients with high-risk BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without Ta or T1 (papillary) tumors.¹

The next steps for BOND-003 involve the treatment extension phase and the addition of a papillary-only cohort. The phase 3 PIVOT-006 study is also launching. This trial is comparing Transurethral Resection of Bladder Tumor (TURBT) followed by adjuvant cretostimogene grenadenorepvec versus TURBT followed by observation for the treatment of participants with intermediate-risk NMIBC.

The designations, which will expedite the development and regulatory review of cretostimogene grenadenorepvec in this setting, are supported by results from the phase 3 BOND-003 trial (NCT04452591), which showed that 75.7% (95% CI, 63-85) of patients treated with cretostimogene grenadenorepvec reached a complete response at any time point. The responses were durable with 74.4% of the complete responses lasting for at least 6 months.²

“Receiving both FDA Fast Track and Breakthrough Therapy Designation is an important milestone in the development of cretostimogene grenadenorepvec and for patients with bladder cancer who urgently need more therapeutic options,” Ambaw Bellete, president & chief operating officer, CG Oncology, the developer of cretostimogene grenadenorepvec, stated in a press release.¹

“We are encouraged by this momentum following our recent announcement of first results from our Phase 3 BOND-003 study for patients with high-risk BCG-unresponsive NMIBC. CG Oncology looks forward to working with the FDA to advance cretostimogene grenadenorepvec as a potential backbone therapy in bladder cancer. We would like to thank the patients, caregivers, investigators and their staff who have participated in the clinical trials,” added Bellete.

To enroll in the BOND-003 trial, patients had to have pathologically confirmed high-risk NMIBC with CIS +/- Ta/T1 that is unresponsive to BCG treatment; an ECOG performance status of 0 to 2; and not be eligible for or refuse to receive a radical cystectomy. Patients were required to have all Ta/T1 disease resected prior to receiving treatment.

Overall, 116 patients with BCG-unresponsive high-risk NMIBC have been enrolled on the trial, and the efficacy data presented at the SUO meeting were from the interim analysis of the first 66 patients at a cutoff date of October 5, 2023.

The 66 patients comprised 50 males and 16 females. The median patient age was 73 years (range, 49-90). Eighty percent of patients were aged >65 years. Fifty-three patients (80%) had an ECOG performance status of 0 and 13 patients (20%) had an ECOG performance status of 1. The median number of prior BCG instillations was 14.4 (range, 7-14). Regarding staging, 2 patients had CIS with T1, 10 patients had CIS with Ta HG, and 54 patients had CIS.

In the study design, the oncolytic immunotherapy is administered beginning with a weekly induction regimen lasting 6 weeks. This is followed by 3 weekly maintenance instillations at months 3, 6, 9, 12, and 18. Patients who continue to have high-grade disease at 3 months are eligible to receive a re-induction regimen of 6 weeks of weekly cretostimogene grenadenorepvec.

Notably, data from the interim analysis showed that 31% of patients who did not respond to their first course of treatment were able to be salvaged with re-induction.

The primary end point of the trial is the rate of complete responses achieved at any time on study. Secondary end points include the complete response rate at 12 months, duration of response, progression-free survival, cystectomy-free survival, and safety. months

The complete response rate at 3 months was 68.2% (n = 45) and the complete response rate at 6 months was 63.6% (n = 42).

The safety population included 112 patients. Most adverse events (AEs) were grade 1/2. The most common treatment-related AEs (TRAEs) were bladder spasm (20.5%), pollakiuria (16.1%), dysuria (14.3%), micturition urgency (11.6%), and hematuria (10.7%).

Two patients (1.8%) experienced grade 2 serious TRAEs and no patients had grade ≥3 TRAEs. There were no treatment-related discontinuations and no patient deaths.

The next steps for BOND-003 involve the treatment extension phase and the addition of a papillary-only cohort. The phase 3 PIVOT-006 study is also launching. This trial is comparing Transurethral Resection of Bladder Tumor (TURBT) followed by adjuvant cretostimogene grenadenorepvec versus TURBT followed by observation for the treatment of participants with intermediate-risk NMIBC.

References

1. CG Oncology. CG Oncology Receives Both FDA Fast Track and Breakthrough Therapy Designation for Cretostimogene Grenadenorepvec in High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer. Published online and accessed December 5, 2023. https://cgoncology.com/cg-oncology-receives-both-fda-fast-track-and-breakthrough-therapy-designation-for-cretostimogene-grenadenorepvec-in-high-risk-bcg-unresponsive-non-muscle-invasive-bladder-cancer/

2. Tyson M, Uchio E, Jong-Kil N, et al. First results from BOND-003, a Phase 3 study of intravesical Cretostimogene grenadenorepvec monotherapy for patients with high-risk BCG- unresponsive Non-Muscle Invasive Bladder Cancer. Presented at: 2023 Society of Urologic Oncology Annual Meeting. November 28 – December 1, 2023; Washington, DC. LBA 3396.