Chemoablation with oral erdafitinib in recurrent FGFR3 -altered non–muscle-invasive bladder cancer: A phase II window-of-opportunity trial.

4623 Background: Non-muscle invasive bladder cancer (NMIBC) frequently recurs despite intravesical treatments, necessitating repeated transurethral resections of bladder tumors (TURBT). FGFR3 alterations are common in NMIBC and may be a potential therapeutic target. Erdafitinib, a pan-FGFR inhibitor, is approved for metastatic urothelial cancer, but its efficacy as a chemoablative agent in recurrent NMIBC is not yet established. This trial evaluates the efficacy of oral erdafitinib as a chemoablative treatment in patients with recurrent FGFR3-altered NMIBC. Methods: Patients with recurrent NMIBC and FGFR3 alterations detected with MSK-IMPACT were given oral erdafitinib (6 mg daily) for ~28 days before TURBT. Tumor response was assessed using RECIT-Bladder criteria, and tissue, blood, and urine samples were collected for pharmacodynamic analyses and biomarker exploration. Toxicities were graded using CTCAE v5.0. Results: A total of 20 patients with recurrent NMIBC and confirmed FGFR3 mutations were enrolled in the study. The most common mutations were S249C (n=12), Y373C (n=3), and R248C (n=3). Most patients (70%) had a history of low-grade Ta (LG Ta) tumors. All patients had received at least one prior intravesical therapy, with 55% having undergone multiple courses of BCG, gemcitabine, mitomycin, or combination regimens. The objective response rate (ORR) was 75% (15/20), with complete response (CR) achieved in 11 patients (55%). No grade ≥3 toxicities were observed. Conclusions: Oral erdafitinib demonstrated efficacy in reducing tumor burden in select FGFR3-altered NMIBC in this window-of-opportunity trial. Clinical trial information: NCT04917809 .