Dr Li on Safety Data Derived From the CORE-001 Trial in BCG-Unresponsive NMIBC

Roger Li, MD, genitourinary oncologist, Moffitt Cancer Center, discusses safety data from the final analysis of the phase 2 CORE-001 trial (NCT04387461) investigating cretostimogene grenadenorepvec plus pembrolizumab (Keytruda) in patients with bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). He also highlights the clinical implications of the data.

At the 2024 ASCO Annual Meeting, Li and colleagues presented findings from the open-label trial, which demonstrated that patients with BCG-unresponsive CIS with or without papillary disease in the intention-to-treat population (n = 35) had a 12-month complete response (CR) rate of 57.1% (95% CI, 39.5%-73.2%). The rate of CR observed at any time during the study was 82.9%. Both these rates were notably higher than the CR rate achieved with pembrolizumab monotherapy in the phase 2 KEYNOTE-057 trial (NCT02625961).

In CORE-001, cretostimogene grenadenorepvec was administered intravesically as a 6-week induction regimen, which was followed by 3 weekly maintenance doses at months 3, 6, 9, 12, and 18. Patients who exhibited high-grade or persistent CIS at the 3-month assessment had the option for reinduction. Pembrolizumab was administered intravenously every six 6 weeks for up to 24 months. The primary end point for the first quarter of the trial was CR at 12 months.

The safety data from the study importantly demonstrate that there was no synergistic toxicity observed with the agents in the combination regimen, Li begins. The safety profile aligns closely with what has been reported in previous pembrolizumab monotherapy trials, indicating no unexpected adverse effects (AEs), he reports. Overall, the treatment was well tolerated, with an approximate 14.3% incidence of grade 3 serious AEs, Li adds.

This combination regimen is exciting, as it has generated efficacy extending out to 2 years and potentially even beyond, he continues. This combination may represent a new treatment option for patients with BCG-unresponsive NMIBC with CIS, Li notes. Li concludes by stating that he is enthusiastic about these results and eager to see what the future holds for this treatment approach.