MRD Assessment Informs RFS Outcomes With Cretostimogene Grenadenorepvec in BCG-Unresponsive NMIBC

NMIBC | Image Credit: © Sebastian Kaulitzki – stock.adobe.com

Minimal residual disease (MRD) negativity was associated with improved high-grade recurrence-free survival (RFS) vs MRD positivity in patients with high-risk, Bacillus Calmette–Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) who received at least 1 dose of cretostimogene grenadenorepvec (P < .001), according to an analysis from the phase 3 BOND-003 (NCT04452591) and phase 2 CORE-001 (NCT04387461) trials presented at the 2025 American Urological Association Annual Meeting.1

“Cretostimogene [grenadenorepvec] is a highly effective and well tolerated treatment regimen. Patients stratified as MRD positive or negative, highly correlated with durable 12-month RFS,” Colin P.N. Dinney, MD, lead study author and chairman of the Department of Urology, Division of Surgery, The University of Texas MD Anderson Cancer Center in Houston, and coauthors wrote in a poster shared during the meeting.

Cretostimogene grenadenorepvec is an oncolytic immunotherapy that operates through a combined mechanism of action, selectively replicating in and lysing cancer cells while amplifying the immune response against bladder tumors.

In January 2024, cretostimogene grenadenorepvec received fast track and breakthrough therapy designations from the FDA for use as a potential treatment approach for patients with high-risk BCG-unresponsive NMIBC with carcinoma in situ with or without Ta or T1 tumors.2

Both designations were supported by data from CG Oncology–led clinical trials showing clinical benefit characterized by complete responses (CRs) and an acceptable safety profile.

As part of the present analysis investigators compiled data on patients who had received at least 1 dose of cretostimogene grenadenorepvec and had MRD testing from BOND-003 (n = 64) and CORE-001 (n = 35).1 The respective studies evaluated the agent as monotherapy and in combination with pembrolizumab (Keytruda) in patients with high-risk, BCG-unresponsive NMIBC.

Topline findings from BOND-003 demonstrated that 74.5% (n = 82/110; 95% CI, 65.4%-82.4%) of patients achieved a CR at any time.3 Final results from CORE-001 revealed that the CR rate at any time was 82.9% (n = 29/35; 95% CI, 70%-95%).4

For the pooled analysis molecular response was based on change in MRD during treatment, and correlations between MRD and clinical response were evaluated.1 UroAmp was used to measure MRD by assessing genomic disease burden and ranking a sample’s variant allele frequency (VAF) percentile relative to a reference training set.

The following variants were evaluated: TERT, TP53, PLEKHS1, KMT2D, KDM6A, aneuploidy, ARID1A, PIK3CA, ERBB3, RXRA, CREBBP, ERBB2, ZFP36L1, RB1, FAT1, SOX4, STAG2, SPTAN1, TSC1, RHOB, ELF3, KMT2C, NIT1, SPAG1, and TPTE.

Investigators noted that the pooled population of patients from both trials with BCG-unresponsive disease reflected a higher-risk cohort compared with other similar series, with an MRD-positivity rate of 85.7%.

Additionally, investigators observed that a dramatic loss of aneuploidy reduced the risk of progression.

“VAF and MRD [were] prognostic for recurrence. [We also saw a] notable reduction in VAF in re-induced patients. Longitudinal MRD assessment may inform future innovative clinical trials designs to prioritize monotherapy vs combination therapy,” the study authors concluded.

Disclosures: No disclosures were listed for Dinney.

References

1. Dinney CPN, Li R, Tyson MD, et al. Translational correlates using minimal residual disease to assess cretostimogene grenadenorepvec: analysis from the BOND-003 and CORE-001 clinical trials. Presented at: American Urological Association Annual Congress; April 26-29, 2025; Las Vegas, NV. IP02-28.
2. 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. CG Oncology. December 5, 2023. Accessed April 26, 2025. 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/
3. CG Oncology announces Bond-003 topline results. News release. CG Oncology. December 5, 2024. Accessed April 26, 2025. https://cgoncology.com/cg-oncology-announces-bond-003-topline-results/#:~:text=97.3%25%20of%20patients%20completed%20all,urgency%2C%20dysuria%2C%20and%20hematuria
4. Li R, Shah PH, Stewart TF, et al. Final results of CORE-001: A phase-2, single arm study of cretostimogene grenadenorepvec in combination with pembrolizumab in patients with BCG-unresponsive, non-muscle invasive bladder cancer with carcinoma in situ. J Clin Oncol. 2024;42(suppl 16):4601. doi:10.1200/JCO.2024.42.16_suppl.4601