Dr Li on Cretostimogene Grenadenorepvec Plus Pembrolizumab in BCG-Unresponsive NMIBC

Roger Li, MD, genitourinary oncologist, Moffitt Cancer Center, discusses findings 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).

These findings were presented at the 2024 ASCO Annual Meeting. The primary end point of CORE-001 was 12-month complete response (CR) rate, and investigators aimed to improve upon response rates seen with pembrolizumab monotherapy in the phase 2 KEYNOTE-057 trial (NCT02625961), Li begins. In cohort A of KEYNOTE-057, which consisted of patients with high-risk, BCG-unresponsive NMIBC with CIS, the 12-month CR rate was 46%. In CORE-001, the 12-month CR rate with the combination (n = 35) was 57.1% (95% CI, 39.5%-73.2%). Overall, 82.9% of patients achieved a CR at any time.

Additionally, responses in CORE-001 were durable, Li says. A total of 54.3% (95% CI, 36.9%-70.8%) of patients had a CR at 24 months, and 95.1% of the patients who achieved a CR at 12 months continued to have a CR at 24 months. The Kaplan Meier recurrence-free survival (RFS) rates in the combination arm were 77.3% (95% CI, 58.1%-88.5%) at 12 months and 69.6% (95% CI, 49.4%-83.0%) at 24 months. The median duration of response (DOR) was not reached but was at least 21 months. The 12-month DOR rate was 81.6% (95% CI, 61.3%-91.9%), and the 24-month DOR rate was 77.3% (95% CI, 56.2%-89.1%).

Importantly, no patients developed MIBC or metastatic urothelial cancer during treatment with the combination, including patients who underwent radical cystectomy, Li emphasizes. Therefore, cretostimogene grenadenorepvec plus pembrolizumab is an ideal regimen to offer to patients who want to prevent their disease from progressing to MIBC or metastatic disease and who can tolerate the minimal amount of adverse effects that were observed in CORE-001, Li explains. However, these findings need to be validated in larger studies, he concludes.