Status:
Completed
Clinicaltrials.gov identifier:
Sponsor:
CG Oncology, Inc in collaboration with Merck
Study Design:
Core-1 is a single arm phase II study. CG0070 was administered intravesically (IVE) weekly x 6. If the patient demonstrates persistent high-grade disease at Week 12, the patient will receive another cycle of 6 weekly treatments. If there is no disease present at Week 12 (e.g., CR) then the patient will receive 3 weekly treatments. Beginning at Week 24, patients will receive 3 weekly treatments every 3 months through Week 48 and then every 24 weeks thereafter. Pembrolizumab was administered intravenously every 3 weeks for up to 2 years and was started on day 1.
Rationale:
Patients with BCG unresponsive disease have limited treatment options. Cretostimogene grenadenorepvec (CG0070) is a novel intravesical viral oncolytic therapy that has demonstrated efficacy in BCG unresponsive disease as a single agent. The addition of pembrolizumab may augment the immune response triggered by CG0070 and thereby, enhance efficacy. This trial evaluates the combination of CG0070 and pembrolizumab.
Endpoints:
Complete response rate.
Comments:
This small phase II study is encouraging and demonstrates higher CR rates than are seen with CG0070 or pembrolizumab alone. The current landscape of approved agents for BCG-unresponsive NMIBC may quickly expand beyond single agents to effective combination regimens. It is important to note that although the side effect profile was not any worse with combination therapy in this study, there are still rare, but potentially significant side effects that are possible with systemic therapies such as pembrolizumab.
Results:
Using a data cut-off of March 3, 2023, 34 patients were evaluable for efficacy with a minimum of 3-months of follow up. At the initial 3-month timepoint, 29 of 34 (85%) patients achieved a CR. Of those patients evaluable for CR at additional timepoints, 82% (n=27/33) have also maintained a CR through 6 months, 81% (n=25/31) through 9 months and 68% (n=17/25) at the 12-month assessment. The combination of CG0070 and pembrolizumab has been well tolerated. The most common treatment-related AEs reported include transient grade 1-2 local genitourinary symptoms.
