According to results from a cohort of the phase 1/2 ADAPT-BLADDER trial, durvalumab plus intravesical gemcitabine and docetaxel showed promise for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer.

Noah M Hahn, MD, Johns Hopkins University, Baltimore, Maryland, first presented these data at the 2025 American Society for Clinical Oncology (ASCO) Genitourinary Cancers Symposium.

Dr Hahn and coauthors wrote, “A critical need persists to develop treatments for BCG-unresponsive non-muscle invasive bladder cancer patients.” They added that intravesical gemcitabine and chemotherapy and intravenous agents targeting the PD-(L)1 immune checkpoint have both demonstrated complete responses (CRs) in BCG-[unresponsive] NMIBC investigations.”

The multi-arm, multi-stage ADAPT-BLADDER trial was designed to investigate the safety and efficacy of durvalumab, durvalumab plus BCG therapy, and durvalumab plus external beam radiation therapy (EBRT). These results are from phase 1 and phase 2 expansion arms with Cohort 4 of this trial. There were 40 patients enrolled in Cohort 4, receiving 1500 mg durvalumab on day 1 of each 4-week cycle for up to 6-cycles, and intravesical gemcitabine plus docetaxel weekly for the first 6 weeks. Maintenance therapy with monthly gemcitabine-docetaxel was encouraged but not required for patients who achieved a complete response.

During phase 1, there were no dose-limiting toxicities reported. Of the 27 patients who were evaluable at report, 24 (89%) achieved a complete response. There was 1 patient who progressed to muscle invasion while on study treatment. Evaluation for complete response and durability of response is ongoing for those patients still on study treatment. There were 2 patients who experienced a grade 3 adverse event (sepsis; pneumonitis), and 1 who experienced a grade 4 adverse event (cough). There was 1 death while on study, due to retroperitoneal bleed unrelated to study therapy.

According to Dr Hahn et al, “combination treatment with durvalumab plus intravesical gemcitabine and docetaxel demonstrates promising clinical efficacy with a high complete response rate.” They added that the safety profile was “consistent with prior durvalumab trial experiences.”

Source:

Hahn NM, Zahurak M, Kaimakliotis HZ, et al. A phase 1/2 trial of durvalumab plus intravesical gemcitabine and docetaxel in BCG-unresponsive non-muscle invasive bladder cancer patients (HCRN GU16-243: ADAPT-BLADDER Cohort 4). Presented at 2025 ASCO Genitourinary Cancers Symposium. February 13-15, 2025; San Francisco, CA. Abstract 667.

Hahn NM, O’Donnell MA, Efstathiou JA, et al. A phase 1 trial of durvalumab in combination with Bacillus Calmette-Guerin (BCG) or external beam radiation therapy in patients with BCG-unresponsive non-muscle invasive bladder cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study. Euro Urol. 2023; 83(6). doi:10.1016/j.eururo.2023.01.17