Phase II Study Evaluates Durvalumab for BCG-Unresponsive Bladder Cancer

Purpose: The study aimed to evaluate the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, in patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) containing carcinoma in situ (CIS).

Patients and Methods: Patients received durvalumab intravenously at 1,500 mg every 4 weeks for up to 12 months. The primary endpoint was the complete response (CR) rate at month 6, determined by negative cystoscopy, urine cytology, and absence of high-grade recurrence on bladder mapping biopsy. The study employed a Simon two-stage design, with the trial potentially stopping if ≤3/13 patients achieved CR in the first stage.

Results: From March 8, 2017, to January 24, 2020, 17 patients were enrolled, with 4 withdrawing after a positive bladder biopsy for CIS at month 3. Two out of 17 patients (12%) achieved a CR at month 6, with response durations of 10 and 18 months, respectively. Adverse events included a single grade 3 lipase elevation attributed to durvalumab, and immune-related adverse events were observed in 41% of patients. Pretreatment, only one patient had high programmed death-ligand 1 expression. RNA sequencing revealed elevated complement activation genes posttreatment and enrichment of tumor-associated macrophage signature.