Combining Durvalumab With Intravesical Therapy in NMIBC: High Response Rates Observed

Because intravesical gemcitabine with docetaxel (gem/doce) and intravenous programmed cell death ligand (PD-L1) inhibitors have shown promising complete response (CR) rates in BCG-unresponsive non–muscle invasive bladder cancer (NMIBC), new research presented at the American Society of Clinical Oncology 2025 Genitourinary Cancers Symposium evaluated the clinical efficacy and safety of combining durvalumab with intravesical gem/doce in a cohort from the ADAPT-BLADDER multi-arm study’s phase I and II expansion arms.

In phase I, patients with BCG-unresponsive NMIBC were enrolled using a 6+3+3 design to determine safety. Additional patients were enrolled in phase II to evaluate the primary endpoint of CR rate in the overall study population and to estimate CR rate among patients with carcinoma in situ (CIS).

Patients received 1500 mg of durvalumab intravenously on day 1 of each four-week cycle for up to six cycles. Each patient also received 1,000 mg of intravesical gemcitabine with 37.5 mg of docetaxel weekly for the first six weeks. Patients achieving a CR were encouraged, but not required, to have monthly gem/doce maintenance therapy. Cystoscopic and urine cytology assessments were performed every three months during the first year, with a mandatory biopsy at 12 months for patients who were responding to treatment. Toxicity was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.

Between January 2022 and October 2024, 40 patients were enrolled from six sites: 12 patients were in phase I and 28 patients were in phase II. A total of 8 patients had CIS, 7 had high-grade T1 with CIS, 6 had high-grade Ta with CIS, 13 had high-grade Ta, and 6 had high-grade T1 disease.

No dose-limiting toxicities were observed in the phase I portion of the study. Among 27 patients (15 with CIS, 12 with papillary disease) who were evaluable for response at the August 2024 data lock, a CR was achieved in 24 (89%), including 87% (13 of 15) of patients with CIS and 92% (11 of 12) of those with papillary disease. Assessment of patients still undergoing study treatment for CR and response durability is ongoing. One patient (4%) experienced progression to muscle-invasive disease while receiving study treatment.

The highest-grade treatment-related adverse events observed were grade 1 in 12 (36%) patients, grade 2 in 11 (33%) patients, grade 3 in 2 (6%) patients (sepsis in 1 and pneumonitis in 1), and grade 4 in 1 (3%) patient (cough). One on-study death occurred due to a retroperitoneal bleed, which was deemed unrelated to study therapy.

The combination of durvalumab with intravesical gemcitabine and docetaxel demonstrates strong clinical efficacy, achieving a high CR rate, and the type, frequency, and severity of adverse events were consistent with prior durvalumab trial data.