Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
Cold Genesys, Inc
Enrollment:
66
Study Design:
The Phase II single-arm multicenter trial targeted BCG unresponsive high-grade NMIBC patients who refused radical cystectomy. In the reported trial, interim results were published in 45 patients treated on the trial with at least 6 months of follow-up.
Rationale:
CG0070 is a replication-competent oncolytic adenovirus that selectively replicates in retinoblastoma (Rb) pathway-defective cells that are often present in bladder cancer. The adenovirus also contains a transgene for granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that can active the immune system. CG0070 works by 2 major mechanisms: 1) induction of tumor lysis by selective replication in Rb-deficient tumor cells and 2) local GM-CSF production that augments immunogenic cell death.
Endpoints:
The primary endpoint was 6-month complete response (CR) rate defined by absence of disease on cystoscopy, cytology, and random biopsies.
Comments:
This trial is limited for many reasons including small numbers of patients, an interim analysis, and no comparison a control group given the heterogeneity of this disease and the multiple pathologic cohorts. Nevertheless, important takeaways from this interim analysis are that 1) CIS tumor respond best to this therapy and 2) pure T1 patients should be followed closely and counseled extensively on the need for early cystectomy. Finally, with an explosion of clinical trials in BCG unresponsive high grade NMIBC, it is important to remember that there is a real, albeit low risk of progression to muscle invasion.
Results:
The disease characteristics of the 45 patients consisted of 24 pure CIS, 8 CIS + Ta, 4 CIS + T1, 6 Ta, and 3 T1. The overall 6-month complete response (CR) rate was 47% for all patients. CR was highest in pure CIS patients at 58% and lowest in pure Ta/T1 patients at 33%. Of note, none of the 3 pure T1 patients had a CR at 6 months and one patient (with Ta and T1 disease) progressed to muscle invasion. The most common treatment-related adverse events (AEs) were bladder spasms (36%), hematuria (28%), and dysuria (25%). However, none of the patients experienced grade 4-5 AEs.
