Cretostimogene Monotherapy Achieves 75.2% Complete Response in High-Risk NMIBC Unresponsive to BCG

CG Oncology, Inc. reported that its Phase 3 BOND-003 study showed promising results for cretostimogene monotherapy in high-risk Non-Muscle Invasive Bladder Cancer (NMIBC) unresponsive to Bacillus Calmette Guerin (BCG). According to the data, 75.2% of patients (79 out of 105, with a 95% confidence interval between 65-83) achieved a complete response (CR) by the cutoff date of April 1, 2024. These findings were presented at the 2024 American Urological Association (AUA) Annual Meeting by Dr. Mark D. Tyson from the Mayo Clinic.

Cretostimogene showed durability with 29 patients maintaining complete response for 12 months or more, while 22 patients' ongoing responses were still being evaluated as of the data cutoff. The median duration of response (DOR) was not reached, but 92.4% cystectomy-free survival was observed, and patients with CR did not undergo radical cystectomy or experience nodal or metastatic progression.

Cretostimogene is an experimental oncolytic immunotherapy known for inducing selective oncolysis and strong anti-tumor immune responses. It is currently being tested in the BOND-003 trial (NCT04452591), involving 112 patients from North America and the Asia-Pacific region. The primary endpoint of the study is CR at any time, with DOR as a secondary endpoint. Participants have previously received both intravesical chemotherapy and systemic immunotherapy.

No Grade 3 or higher treatment-related adverse events (TRAEs) or deaths were reported. However, 1.8% of patients experienced serious TRAEs (Grade 2). The treatment completion rate was high, with 94.5% of patients completing all intended treatments. TRAEs occurred in 70 patients (62.5%), with the most common being bladder spasm, frequent urination, painful urination, urgency in urination, and blood in the urine as of January 31, 2024.

Dr. Gary D. Steinberg from the Rush University Medical Center noted that the positive data presented at the AUA 2024 meeting support cretostimogene as a vital monotherapy for BCG-unresponsive NMIBC patients, potentially reducing the need for bladder removal surgery. The innovative approach may become a favored option for these patients, offering a significant improvement in outcomes.

Ambaw Bellete, President and COO of CG Oncology, emphasized that the latest data reinforce cretostimogene's potential to improve patients' quality of life and outcomes. The company looks forward to a regulatory approval submission with expected topline data from the BOND-003 trial by the end of 2024.

In December, the FDA granted Fast Track and Breakthrough Therapy designations to cretostimogene for high-risk BCG-unresponsive NMIBC with carcinoma in situ, with or without Ta or T1 papillary tumors.

Cretostimogene is also being evaluated in other clinical settings, including a Phase 2 trial (CORE-001) in combination with pembrolizumab and a Phase 3 trial (PIVOT-006) in intermediate-risk NMIBC patients. Additionally, an investigator-sponsored study is assessing its efficacy in combination with nivolumab for muscle-invasive bladder cancer.

Bladder cancer is estimated to affect more than 83,000 individuals in 2024, with NMIBC accounting for approximately 75% of newly diagnosed cases. Bladder cancer ranks as the sixth most common cancer in the United States, predominantly affecting men.

CG Oncology remains focused on advancing its clinical programs to provide innovative, bladder-sparing immunotherapies that offer enhanced quality of life for bladder cancer patients.