(UroToday.com) At the 2022 American Society of Clinical Oncology Annual Meeting held in Chicago and virtually, the poster session focused on Kidney and Bladder cancers on Saturday afternoon included a presentation from Dr. Roger Li discussing the role of neoadjuvant CG0070 and nivolumab as neoadjuvant therapy in patients with muscle invasive bladder cancer (MIBC) who are ineligible for cisplatin-based chemotherapy.
Cisplatin-based neoadjuvant chemotherapy prior to radical cystectomy is the standard of care for patients with localized MIBC. However, many patients are ineligible for cisplatin and there are no proven agents with benefit in the neoadjuvant setting. Thus, these patients are recommended to proceed directly to cystectomy. However, novel treatment paradigms may offer the potential for these patients to benefit from neoadjuvant treatment. CG0070 is a replication-competent oncolytic adenovirus engineered to target RB deficient tumor cells and to express GM-CSF.
Among patients with BCG-exposed high risk non-muscle invasive bladder cancer, CG0070 has previously demonstrated safety and efficacy through tumor lysis and anti-tumor immune activation. Thus, the authors sought to assess its safety and efficacy, in combination with nivolumab, neoadjuvant therapy for MIBC in cisplatin-ineligible patients.
To do so, the authors prospectively enrolled cisplatin-ineligible patients with MIBC (cT2-4a, N≤1) (NCT04610671). Patients received 6 weekly intravesical CG0070 (1x1012vp) instillations and 2 doses of nivolumab at weeks 2 and 6, followed by radical cystectomy (RC).
The primary objective was to assess the safety of this combination of CG0070 as nivolumab as neoadjuvant therapy, measured using CTCAEv5.0. The secondary objective was to assess pathologic response (PaR) (pT0N0) while further exploratory objectives included the assessment of correlation between PaR with baseline 1) E2F expression; 2) immune infiltration; 3) PD-L1 expression; and 4) TLS expression. In this abstract, the authors report sesults from a prespecified interim analysis following accrual of 15 patients.
The authors enrolled 15 patients between November 2020 and January 2022. The median age of included patients was 75.5 year, 73% were male, and 47% had greater than cT2 disease. In the endo, 1 patient refused RC but was included in the ITT population.
The authors did not observe any dose limited toxicities (DLTs). The overall rate of grade 3-4 AEs was 10/15 (75%), and the vast majority were related to RC (90%). Immune related AEs were seen in one patient, who experienced grade 2 autoimmune thyroiditis. Further, there was no delay in time to RC and no unexpected surgical complications from treatment. A complete pathological response (PaR) was observed in 7 of 13 (54%) evaluable patients, including the patients who had negative post-treatment biopsy and refused RC.
Thus, the authors conclude that neoadjuvant CG0070 and nivolumab is safe and effective in cisplatin-ineligible patients with MIBC.
Presented by: Roger Li, MD, Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 3 – Mon, June 7, 2022.