Investigational Tx shows promise for BCG-unresponsive NMIBC

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An investigational oncolytic immunotherapy based on a modified common cold adenovirus now is showing promise for treating bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer (NMIBC).

New interim findings presented at the AUA annual meeting in San Francisco demonstrated that intravesical CG0070, which is a selective oncolytic adenovirus that exploits retinoblastoma pathway defects, produced an overall 30% complete response rate at 12 months for patients with high-risk BCG-unresponsive NMIBC and a 48% complete response rate for those with BCG-refractory disease.

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“It is certainly innovative and a promising approach,” said study investigator Gary Steinberg, MD, of the University of Chicago. CG0070 contains a cancer-specific promoter and a GM-CSF transgene. The company developing it says CG0070 is designed to work in two important and complementary ways. It replicates inside the tumor’s cells causing tumor cell lysis and immunogenic cell death. Then, the rupture of the cancer cells releases tumor-derived antigens with GM-CSF, stimulating a systemic anti-tumor immune response.

Dr. Steinberg and his team previously demonstrated promising 6-month response using this product. Longer term efficacy was unknown, so the authors performed a 12-month evaluation as part of a phase II trial for CG0070 in patients with BCG-unresponsive NMIBC who refused cystectomy. The cohort included 67 patients with residual BCG-unresponsive high-grade Ta, T1, or CIS ± Ta/T1. All the patients in this study were unable to achieve disease-free state at 6 months after adequate BCG (BCG-refractory) or they developed recurrence after complete response (CR) to BCG (BCG-relapsed).

Next:What the authors foundFor this current investigation, the authors defined CR as no disease on cystoscopy, cytology, and/or random biopsies. At interim analysis of 61 patients, the overall 12-month CR rate was 30%. The authors found that 45 patients (27%) with CIS-containing tumors had a CR at 12 months. They also found that 16 patients (38%) with pure Ta/T1 had a CR at 12 months. None of the six patients with T1/CIS or Ta/CIS had a CR at 12 months. The interim results also showed that 25 BCG-refractory patients (48%) had a CR at12 months and 31 BCG-relapsed patients (19%) had a CR at 12 months.

In this cohort, 10 patients underwent cystectomy and six of these patients had muscle-invasive disease. The adverse events (AEs) were found to be Grade 1-3 at 12 months and the immunologic AEs included influenza type illness (7%), fatigue (4%), and chills (1%). There were five deaths that were secondary to progressive urothelial carcinoma, esophageal carcinoma, lung carcinoma, and cardiac disease, according to the authors.

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“This is a burgeoning area and this has shown the most promise of any product for patients with BCG-unresponsive non-muscle-invasive bladder cancer,” Dr. Steinberg said in an interview with Urology Times.

CG0070 is also being investigated in a phase I/II study evaluating the safety and efficacy of the neo-adjuvant combination of CG0070 plus anti-CTLA-4 in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for platinum-based chemotherapy. One of the primary endpoints is to evaluate the efficacy of this intervention to increase the expression of PD-L1 in the primary tumor. Positive results theoretically increasing the chance to further use an anti-PD1 or anti-PD-L1 blocker as an adjuvant in MIBC patients, who usually are deficient in PD-L1 and prone to disease recurrence.

Cold Genesys provided funding for the study.