Introduction

CG0070 is a replication selective oncolytic adenovirus that destroys bladder tumor cells through their defective retinoblastoma pathway. Prior reports have shown promising activity in patients with high-grade NMIBC who previously did not respond to BCG. However, limited accrual has hindered analysis of efficacy, particularly for pathologic subsets. We evaluated interim results of a phase II trial for intravesical CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy.

Methods

At interim analysis, thirty-six patients with residual high grade Ta, T1, or CIS ± Ta/T1 had 6 month follow-up in this phase II single arm multicenter trial (NCT02365818). All patients received at least 2 prior courses of intravesical therapy for CIS, with at least 1 of them being a course of BCG. Patients had either failed BCG induction therapy within 6 months or had been successfully treated with BCG with subsequent recurrence. Complete response (CR) at 6 months was defined as absence of disease on cytology, cystoscopy, and random biopsies.

Results

Of 36 patients there were 18 CIS, 4 CIS + Ta, 3 CIS + T1, 8 Ta, 3 T1 (Figure 1). Overall 6 month CR was 44%. Considering 6 month CR for pathologic subsets: pure CIS was 72.2%, CIS ± Ta/T1 52%, CIS + Ta/T1 0%, pure Ta/T1 27%. In non-responders with CIS, there were 4 patients (22%) with persistent CIS at 6 months, and 1 (5.6%) that progressed to CIS + T1. No patients with pure T1 or CIS + Ta/T1 had 6-month CR. In patients with both CIS + Ta/T1 (n=7), 5 had persistent Ta/T1 ± CIS, while 2 had CIS on biopsy at 6 months. All treatment related adverse events (AEs) at 6 months were Grade 1-3, most commonly urinary: dysuria (47%), bladder spasms (44%), hematuria (36%), and urgency (33%). Immunologic treatment related AEs included fatigue (11%) and chills (5.6%). Grade 3 treatment related AEs included dysuria (5.6%) and hypotension (2.7%). There were no Grade 4/5 treatment related AEs.

Conclusions

This phase II study demonstrates that intravesical CG0070 yielded an overall 44% complete response rate at 6 months for all patients and 52% for patients with CIS, with an acceptable level of toxicity for patients with high-risk BCG-unresponsive NMIBC. There is a particularly strong response and limited progression in patients with pure CIS.

Funding

Cold Genesys