Immune checkpoint blockade holds promise for treating BCG-unresponsive non-muscle invasive bladder cancer. In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive CIS.
Patients with BCG-unresponsive CIS containing non-muscle invasive bladder cancer received durvalumab IV at 1500 mg every 4 weeks for up to 12 months. The primary endpoint was complete response rate at month 6, defined by negative cystoscopy, urine cytology and absence of high-grade recurrence on bladder mapping biopsy. The null hypothesis specified a complete response rate of 18% and alternative hypothesis 40%. According to the Simon 2-stage design, if ≤3/13 patients achieved complete response during stage 1, the trial is stopped due to futility.
Between 03/8/2017 and 1/24/2020, 17 patients were accrued while 4 withdrew from study treatment after bladder biopsy at month 3 was positive for CIS. 2 of 17 (12%) achieved a complete response at month 6, with duration of response of 10 and 18 months, respectively. A single Grade 3 lipase elevation was attributed to durvalumab, and immune related adverse events were observed in 7/17 (41%) patients. Only 1/17 patients had high PD-L1 expression pre-treatment. On RNAseq, complement activation genes were elevated post-treatment, along with enrichment of tumor associated macrophage signature.
Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6mo complete response of 12%. Complement activation is a potential mechanism behind treatment resistance.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2023 Jul 28 [Epub ahead of print]
Roger Li, Wade J Sexton, Jasreman Dhillon, Anders Berglund, Shreyas Naidu, Gustavo Borjas, Kyle Rose, Youngchul Kim, Xuefeng Wang, Jose R Conejo-Garcia, Rohit K Jain, Michael A Poch, Philippe E Spiess, Julio Pow-Sang, Scott M Gilbert, Jingsong Zhang
Moffitt Cancer Center, Tampa, FL, United States., Moffitt Cancer Center, Tampa, Fl, United States., H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, United States., H. Lee Moffitt Cancer Center, Tampa, FL, United States., Duke School of Medicine, Durham, NC, United States., H. Lee Moffitt Cancer Center & Research Inst., Tampa, Florida, United States., H Lee Moffitt Cancer Center, Tampa, FL, United States., Moffitt Cancer Center, Tampa, Florida, United States.