Cretostimogene grenadenorepvec made available through expanded access program

An expanded access program (EAP) for cretostimogene grenadenorepvec has been initiated for adult patients in the US with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) who meet certain program eligibility criteria, CG Oncology, the developer of the therapy, announced in a news release.¹

Data from BOND-003 showed that cretostimogene induced complete responses in three-fourths of patients with BCG-unresponsive NMIBC with CIS.

EAPs grant availability to investigational therapeutics for patients outside of clinical trials for whom there is no comparable or satisfactory alternative options. According to the company, the first patient has been dosed with cretostimogene through the open-label EAP, and enrollment for the program is currently ongoing (NCT06443944).

“Bladder cancer is a highly recurrent disease with few treatment options available to patients,” said Ambaw Bellete, president and chief operating officer of CG Oncology, in the news release.¹ “This program reflects our commitment to patients afflicted with NMIBC and our desire to ensure that they have efficient access to cretostimogene, our novel oncolytic immunotherapy candidate.”

Patients included in the EAP will first receive an induction course of cretostimogene. If there is no disease recurrence present at week 13, patients will then receive 3 weekly treatments up to week 15. If there is disease present at week 13, patients may undergo a second induction course. If no further disease is present after, patients will then receive 3 weekly treatment cycles every 12 weeks through month 12, and then 3 weekly treatment cycles every 6 months to month 24 or until treatment discontinuation.²

Cretostimogene grenadenorepvec is an intravesical oncolytic immunotherapy currently under investigation in the phase 3 trials. BOND-003 (NCT04452591) is a phase 3 trial exploring the therapy in patients with BCG-unresponsive NMIBC. PIVOT-006 (NCT06111235) is a phase 3 study evaluating the therapy in patients with intermediate-risk NMIBC following TURBT. Cretostimogene is also being assessed in combination with nivolumab in an investigator-initiated trial for patients with muscle-invasive bladder cancer.

Data on cretostimogene grenadenorepvec

Phase 3 data from the BOND-003 trial of cretostimogene grenadenorepvec in patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) were recently presented at the 2024 American Urological Association Annual Meeting in San Antonio, Texas.³

Overall, the study showed that the novel oncolytic immunotherapy induced complete responses (CRs) in three-fourths of patients with BCG-unresponsive NMIBC with CIS.

Looking at the efficacy analysis, the overall CR rate at any time point for all patients was 75.2% (95% CI, 65%-83%), according to Mark D. Tyson, II, MD, MPH, who presented the data at the meeting.

Cretostimogene also demonstrated durable responses over time as 53.8% of patients who underwent repeat induction converted to CR. Additionally, a duration of response (DOR) of 6 months or longer was maintained in 52 patients, a DOR of 12 months or longer in 29 patients, and a DOR of 21 months or longer in 14 patients. Currently, 8, 22, and 36 complete responders are still pending for those time points, respectively.

Additional data showed a cystectomy-free survival (CFS) of 92.4% at the 1-year time point. None of the patients with a CR had undergone a radical cystectomy, and there was no nodal or metastatic progression observed. Further, the progression-free survival (PFS) at 12 months was 96.7%.

Regarding safety, cretostimogene has been generally well-tolerated with no grade 3 or greater treatment-related adverse events (TRAEs) and no deaths reported. Most AEs were grade 1 or 2. TRAEs occurred in 70 patients (62.5%) with the most common (greater than 10%) being bladder spasm (23.2%), pollakiuria (19.6%), dysuria (15.2%), micturition urgency (15.2%), and hematuria (14.2%).

In total, 2 (1.8%) grade 2 serious AEs––cystitis and clot retention––were observed, and 1 patient discontinued the trial due to an unrelated AE. Moreover, 94.5% of patients completed all expected treatments.

Overall, BOND-003 is an open-label, single-arm, phase 3 trial that enrolled 112 patients with BCG-unresponsive, high-risk NMIBC across sites in North America and the Asia-Pacific region. Those eligible for enrollment were patients aged 18 years and older with pathologically confirmed high-risk NMIBC with CIS +/- Ta/T1 disease that is unresponsive to BCG treatment. Patients were also required to have an ECOG performance status of 0 to 2.

The primary end point being evaluated in the trial is the rate of CRs reached at any time. Investigators are also evaluating the secondary end points of CR rate at 12 months, DOR, PFS, CFS, and safety.⁴

These data led the FDA to grant both fast track and breakthrough designations to cretostimogene grenadenorepvec for the treatment of BCG-unresponsive NMIBC in December 2023.⁵ CG Oncology and the FDA are continuing to work together to advance cretostimogene grenadenorepvec as a potential backbone therapy in bladder cancer.

References

1. CG Oncology initiates expanded access program for cretostimogene grenadenorepvec. News release. CG Oncology Inc. Published online and accessed June 18, 2024. https://ir.cgoncology.com/news-releases/news-release-details/cg-oncology-initiates-expanded-access-program-cretostimogene

2. An expanded access program of cretostimogene grenadenorepvec for treatment of NMIBC for patients unresponsive to BCG. ClinicalTrials.gov. Last updated June 5, 2024. https://www.clinicaltrials.gov/study/NCT06443944

3. Tyson M, Uchio E, Nam J, et al. Pivotal results from BOND-003:A phase 3, single-arm study of intravesical cretostimogene grenadenorepvec for the treatment of high risk, BCG-unresponsive non-muscle invasive bladder cancer. Presented at: 2024 American Urological Association Meeting; May 3-May 6, 2022; San Antonio, TX.

4. 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 May 3, 2024. https://www.clinicaltrials.gov/study/NCT04452591

5. CG Oncology receives both FDA fast track and breakthrough therapy designation for cretostimogene grenadenorepvec in high-risk BCG-unresponsive non-muscle invasive bladder cancer. News release. December 5, 2023. Accessed June 18, 2024.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/