Study of Enfortumab Vedotin and Pembrolizumab with Radiation Therapy as Bladder-Sparing Treatment for Muscle-Invasive Bladder Cancer

What this Trial Is About

Researchers are evaluating the safety, side effects, best dosing, and effectiveness of combining enfortumab vedotin with pembrolizumab and radiation therapy to treat patients with muscle invasive bladder cancer. This phase IbII trial focuses on patients who are not candidates for standard chemotherapy and surgery or prefer bladder-sparing options. Enfortumab vedotin is a targeted antibody-drug conjugate, and pembrolizumab is an immunotherapy drug that may help the immune system attack cancer cells. The radiation therapy used is intensity-modulated to minimize damage to healthy tissue while targeting the tumor. Participants receive different dose levels of enfortumab vedotin intravenously on days 1 and 8 of 21-day cycles, combined with pembrolizumab given intravenously on day 1 of each cycle. Radiation therapy is delivered once daily for 32 days during the first treatment cycle. The study includes up to 5 cycles of enfortumab vedotin and up to 17 cycles of pembrolizumab, alongside standard procedures like transurethral resection of bladder tumor TURBT, cystoscopy, and imaging. Dose escalation occurs in phase Ib, followed by a dose expansion phase II at the recommended phase II dose. Throughout the study, participants undergo regular assessments including cystoscopy, TURBT, cytology, and imaging to evaluate tumor response and safety. Follow-up visits happen 90 days after treatment completion and then every 12 weeks for up to 5 years. Researchers measure clinical complete response rates, recurrence-free survival, cystectomy-free survival, overall survival, and tumor downstaging. Exploratory analyses include changes in tumor gene expression, immune cell populations, and markers related to treatment effects.

Enfortumab Vedotin and Pembrolizumab Combined With Radiotherapy in Muscle Invasive Bladder Cancer