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Data from A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma <i>In Situ</i> of the Bladder

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Li, R; Sexton, WJ; Dhillon, J; Berglund, A; Naidu, S; Borjas, G; Rose, K; Kim, Y; Wang, X; Conejo-Garcia, JR; Jain, RK; Poch, MA; Spiess, PE ...
October 2, 2023

<div>AbstractPurpose:<p>Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive carcinoma <i>in situ</i> (CIS).</p>Patients and Methods:<p>Patients with BCG-unresponsive CIS-containing NMIBC received durvalumab IV at 1,500 mg every 4 weeks for up to 12 months. The primary endpoint was complete response (CR) 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 CR rate of 18% and alternative hypothesis of 40%. According to the Simon two-stage design, if ≤3/13 patients achieved CR during stage 1, the trial is stopped due to futility.</p>Results:<p>Between March 8, 2017, and January 24, 2020, 17 patients were accrued whereas 4 withdrew from study treatment after bladder biopsy at month 3 was positive for CIS. Two of 17 (12%) achieved a CR 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 programmed death-ligand 1 expression pretreatment. On RNA sequencing, complement activation genes were elevated posttreatment, along with enrichment of tumor-associated macrophage signature.</p>Conclusions:<p>Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6-month CR of 12%. Complement activation is a potential mechanism behind treatment resistance.</p></div>

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Publication Date

October 2, 2023
 

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Li, R., Sexton, W. J., Dhillon, J., Berglund, A., Naidu, S., Borjas, G., … Zhang, J. (2023). Data from A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma <i>In Situ</i> of the Bladder. https://doi.org/10.1158/1078-0432.c.6861175
Li, Roger, Wade J. Sexton, Jasreman Dhillon, Anders Berglund, Shreyas Naidu, Gustavo Borjas, Kyle Rose, et al. “Data from A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma <i>In Situ</i> of the Bladder,” October 2, 2023. https://doi.org/10.1158/1078-0432.c.6861175.
Li R, Sexton WJ, Dhillon J, Berglund A, Naidu S, Borjas G, Rose K, Kim Y, Wang X, Conejo-Garcia JR, Jain RK, Poch MA, Spiess PE, Pow-Sang J, Gilbert SM, Zhang J. Data from A Phase II Study of Durvalumab for Bacillus Calmette-Guerin (BCG) Unresponsive Urothelial Carcinoma <i>In Situ</i> of the Bladder. 2023.

DOI

Publication Date

October 2, 2023