BOND-003: Cretostimogene yields high CR rate, is well tolerated in NMIBC

Results from the phase 3 BOND-003 (NCT04452591) clinical trial evaluating cretostimogene grenadenorepvec for the treatment of high-risk BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) indicate that the treatment is efficacious and well tolerated.¹

“Cretostimogene demonstrates really compelling efficacy with a complete rate any time point of 74.5%...with a strong safety profile,” says Mark D. Tyson, MD, MPH.

The results were presented at the Society of Urologic Oncology 25th Annual Meeting by Mark D. Tyson, MD, MPH, a urologic oncologist at the Mayo Clinic in Phoenix, Arizona.

The study included 112 patients with pathologically confirmed high-risk, BCG-unresponsive NMIBC with CIS +/- high-grade Ta/T1 disease. All high-grade Ta/T1 disease was resected prior to treatment, and mandatory biopsies were performed at 12-month assessment. The induction course for the treatment took place weekly x 6 and, and there was a second induction of weekly x 6 for non-responders that took place at month 3. A maintenance course of treatment was given weekly x 3 Q3M for year 1 and weekly x 3 Q6M for year 2. The primary end point was complete response (CR) at any time, with additional end points including CR at 12 months, duration of response (DOR), recurrence-free survival, progression-free survival, cystectomy-free survival, and safety.

Eighty-three (74.1%) patients were male, and 29 (25.9%) were female. Mean patient age was 72.9 years (SD, 9.19), and median patient age was 74.0 years (range, 43-90 years). Nineteen (17.0%) patients were younger than age 65, 43 (38.4%) were between 65 and 74, and 50 (44.6%) were 75 years of age or older. Median number of prior BCG instillations was 12 (range, 7-66). Twenty-two (19.6%) patients had carcinoma in situ (CIS) with HG Ta/1 at study entry and 90 (80.4%) had CIS alone.

The overall CR rate was 74.5% (95% CI, 65.4%-82.4%). At 12 months, the CR rate was 46% (95% CI, 36.9-56.1) and 50% (95% CI, 39.6-58.9%) by Kaplan-Meier estimate. According to the presentation, there were “25 confirmed CRs that have reached 24-month timepoint and beyond,” with a 24-month CR rate of 41% (95% CI, 30.4-50.8) by Kaplan-Meier estimate.

In addition, Tyson reported that 97.3% of patients were free from progression to muscle-invasive bladder cancer at 12 months. In addition, there was a 12-month 90.0% cystectomy-free survival rate.

According to Tyson, the median DOR was not yet reached but was more than 27 months. The estimated DOR probability was 63.5% (95% CI, 51.2-73.4) at 12 months and 56.6% (95% CI, 43.3-67.8) at 24 months.

Treatment with cretostimogene was well tolerated. There was a 0% rate of grade 3 or higher treatment-related adverse events (TRAEs) or deaths. The majority of AEs were grade 1-2, and no treatment-related discontinuations were reported. A total of 72 (64/3%) patients had at least 1 TRAE of any grade. Any-grade TRAEs that were observed in more than 10% of patients included bladder spasm, pollakiuria, urgency, dysuria, and hematuria.

“In summary, cretostimogene demonstrates really compelling efficacy with a complete rate any time point of 74.5%...with a strong safety profile,” Tyson concluded in his presentation.

In a news release regarding the data, Gary D. Steinberg, MD, praised the results.

“There continues to be a significant need for new treatment options for patients with bladder cancer. Therefore, I am very encouraged by the latest data from the BOND-003 study, which demonstrates cretostimogene’s compelling efficacy as well as its potential to induce a best-in-class durable response in NMIBC patients, with 63.5% of patients remaining in response at 12 months or greater and 56.6% of patients remaining in response at 24 months or greater, by [Kaplan-Meier] estimate. Additionally, 97.3% of patients were free from progression to muscle invasive bladder cancer at 12 months. If approved by the FDA, cretostimogene may represent an important, bladder-sparing, advancement in the bladder cancer treatment paradigm, and meaningfully improve patient outcomes,” said Steinberg.²

Cretostimogene was granted fast track and breakthrough therapy designations by the FDA in December 2023 for patients with high-risk NMIBC. It is also being evaluated in combination with nivolumab (Opdivo) for the treatment of muscle-invasive bladder cancer.

REFERENCES

1. Tyson M, Uchio E, Nam J-K, et al. Topline results from BOND-003: a phase-3 study of intravesical cretostimogene grenadenorepvec for the treatment of high-risk BCG-unresponsive NMIBC with CIS. Presented at: Society of Urologic Oncology 25th Annual Meeting. December 4-6, 2024. Dallas, Texas. Late-breaking abstract

2. Groundbreaking cretostimogene grenadenorepvec monotherapy data demonstrates sustained, durable complete responses in high-risk BCG-unresponsive non-muscle invasive bladder cancer. News release. CG Oncology. December 5, 2024. Accessed December 5, 2024. https://www.globenewswire.com/news-release/2024/12/05/2992219/0/en/Groundbreaking-Cretostimogene-Grenadenorepvec-Monotherapy-Data-Demonstrates-Sustained-Durable-Complete-Responses-in-High-Risk-BCG-Unresponsive-Non-Muscle-Invasive-Bladder-Cancer.html