FDA Grants 2 Designations to Cretostimogene Grenadenorepvec in NMIBC

• This fast track and breakthrough therapy designation granted to cretostimogene grenadenorepvec intends to accelerate the path to the FDA submission.

• Patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) achieved a complete response rate of 75.7% with cretostimogene grenadenorepvec in the the phase 3 BOND-003 trial (NCT04452591).

• Cretostimogene grenadenorepvec was also well-tolerated, with mostly grade 1-2 adverse events (AEs) seen in patients.

A breakthrough therapy designation and fast track designation was granted by the FDA to the oncolytic immunotherapy cretostimogene grenadenorepvec for the treatment of patients with high-risk BCG-unresponsive NMIBC with CIS with or without Ta or T1 (papillary) tumors.¹

Findings from the phase 3 BOND-003 trial support this regulatory decision. In the study, 75.7% (95% CI, 63%-85%) of patients given cretostimogene grenadenorepvec had a complete response (CR) at any time point, and responses were durable. At 3 months, the complete response rate was 68.2% (n = 45) and the complete response rate at 6 months was 63.6% (n = 42). Additionally, 74.4% of the CRs lasted for a minimum of 6 months.²

Data from the interim analysis also showed that a total of 31% of patients who did not respond to their first course of treatment were able to be salvaged with re-induction. In the safety population, which included 112 patients, the majority of AEs were grade 1-2 with the most common treatment-related AEs (TRAEs) being bladder spasm (20.5%), pollakiuria (16.1%), dysuria (14.3%), micturition urgency (11.6%), and hematuria (10.7%). Further, grade 2 serious TRAEs were seen in 2 (1.8%) patients, no patients had grade ≥3 TRAEs, and there were no treatment-related discontinuations or patient deaths.

“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,” said Ambaw Bellete, president and chief operating officer, CG Oncology, the developer of cretostimogene grenadenorepvec, in a press release.¹

Bladder Image: © magicmine stock.adobe.com

The open-label, single-arm, phase 3 BOND-003 study enrolled patients with BCG-unresponsive, high-risk NMIBC across North America and the Asia-Pacific regions.³ Patients were eligible for enrollment if aged 18 years and older with pathologically confirmed high-risk NMIBC with CIS +/- Ta/T1 that is unresponsive to BCG treatment and an ECOG performance status of 0-2. Patients must not be eligible for or refuse to receive a radical cystectomy.

A total of 116 patients with BCG-unresponsive high-risk NMIBC have been enrolled in the trial. Efficacy data from the interim analysis of the study were presented at the Society of Urologic Oncology meeting which included the first 66 patients. At a cutoff date of October 5, 2023, this patient population included 50 male patients and 16 female patients with a median patient age of 73 years (range, 49-90).

Baseline characteristics showed that 80% of patients were aged >65 years. A total of 53 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 installations was 14.4 (range, 7-14). Two patients had CIS with T1, 10 patients had CIS with Ta HG, and 54 patients had CIS.

In the study, treatment with the oncolytic immunotherapy is given to patients in a weekly induction regimen lasting 6 weeks. This is followed by 3 weekly maintenance installations at months 3, 6, 9, 12, and 18. The 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.

The primary end point being evaluated in the trial is the rate of CRs reached at any time, and secondary end points include CR rate at 12 months, duration of response, progression-free survival, cystectomy-free survival, and safety.

“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, in a press release.¹

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. December 5, 2023. Accessed December 6, 2023. https://tinyurl.com/yayb3zhh

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.

3. Study of CG0070 given in patients with non-muscle invasive bladder cancer, unresponsive to bacillus-calmette-guerin (BOND-003). ClinicalTrials.gov. Updated May 12, 2023. Accessed December 6, 2023. https://www.clinicaltrials.gov/study/NCT04452591