Back to 2025 Abstracts
Encore Durability Results From BOND-003 Cohort C- Phase 3, Single-Arm Study of Intravesical Cretostimogene Grenadenorepvec for High-Risk BCG-Unresponsive Non-Muscle Invasive Bladder Cancer with Carcinoma In Situ
Mark Tyson, MD, MPH
1, Edward M. Uchio, MD
2, Jong-Kil Nam, MD
3, Shreyas Joshi, MD
4,
Trinity J. Bivalacqua, MD, MPH5, Gary Steinberg, MD
6, Hiroshi Kitamura, MD
7, Ben Tran, MBBS
8, Roger Li, MD
9.
1Mayo Clinic, Phoenix, AZ, USA,
2University of California Irvine, Irvine, CA, USA,
3Busan National University Yangsan Hospital, Yangsan, Korea, Democratic People's Republic of,
4Emory University School of Medicine, Atlanta, GA, USA,
5University of Pennsylvania, Philadelphia, PA, USA,
6Rush University Medical Center, Chicago, IL, USA,
7University of Toyama, Toyama, Japan,
8Peter MacCallum Cancer Centre, Melbourne, Australia,
9H. Lee Moffitt Cancer Center, Tampa, FL, USA.
BACKGROUND: Considerable unmet medical need exists for bladder-sparing treatment options for patients with HR BCG-UR NMIBC with CIS. Cretostimogene grenadenorepvec, an oncolytic immunotherapy, selectively targets and lyses cancer cells with Retinoblastoma (Rb)-E2F pathway alterations, triggering antitumor immune activation which is further amplified by the GM-CSF transgene. Cretostimogene received US FDA Fast Track and Breakthrough Therapy Designations. BOND-003 (NCT044552591) is a phase-3 study evaluating the efficacy and safety of cretostimogene in patients with HR BCG-UR NMIBC.
METHODS: 112 adults with histologically confirmed HR BCG-UR NMIBC with CIS were enrolled. Treatment consisted of 6-weekly induction doses, followed by maintenance. Re-induction was permitted. Response assessments included cystoscopy, cytology, imaging, and mandatory mapping biopsy at month 12, with centralized pathology review. The primary endpoint was Complete Response at any time.
RESULTS: As of the January 20, 2025 data cutoff, with a median follow-up time of 22.3 months, the CR rate at any time is 75.5% (83/110) (95% CI 66.3-83.2%). The median duration of response is 28 months (95% CI 14.3-NE%) and is on-going. Patients converted to CR (50%,14/28) after re-induction, of whom 64.3% (9/14) remain in a durable complete response. Complete responses are consistent across patient subgroups, including those who received prior intervening therapy, re-induction, or presented with higher-risk phenotypes such as CIS+HGT1. A total of 97.3% (107/110) of patients completed all protocol-defined treatments, demonstrating high patient tolerability. At 24 months, 97.3% (107/110) were free from ≥T2 progression during the treatment phase and 84.5% (93/110) avoided a radical cystectomy. There were with no grade 3+ adverse events related to treatment.
CONCLUSIONS: The consistent and compelling outcomes with intravesical cretostimogene for the treatment of HR BCG-UR NMIBC with CIS compares favorably and offers distinct advantages to existing therapies. Ongoing investigation of cretostimogene monotherapy, and combinations, may address an unmet need for bladder cancer patients.
Back to 2025 Abstracts
