ETCTN 10483: Phase Ib trial of erdafitinib (E) combined with enfortumab vedotin (EV) following platinum and PD-1/L1 inhibitors for metastatic urothelial carcinoma (mUC) with FGFR3/2 genetic alterations (GAs).

• DOI: 10.1200/jco.2025.43.5_suppl.808
• Publication Date: 2025-02-18T14:32:56Z
• Authors: Rohit K. Jain; Faustine Ong; Bishoy Morris Faltas; Scott T. Tagawa; Di Maria Jiang; Jazlyn Heiligh; Syeda Mahrukh Hus...; Youngchul Kim; Lorraine Cheryl P...; Yuanquan Yang; Laura Graham; Waddah Arafat; Timothy Walter Sy...; Monica Sheila Cha...; Jingsong Zhang; Jus Chadha; Guru P. Sonpavde
• Keywords: Metastatic Urothelial Carcinoma; Urothelial cancer

808 Background: Erdafitinib (E) is an approved treatment in patients with mUCwith FGFR 3 GAs after progression on platinum-based chemotherapy (PBC). Enfortumab Vedotin (EV) to treat mUC following prior PBC and PD1/L1 inhibitors or as First-line therapy combination pembrolizumab. Retrospective studies suggest that the activity of EV not compromised by 3/2 GAs. erdafitinib have different mechanisms toxicities are mostly non-overlapping. Hence, there rationale evaluate feasibility E, overcome difficulties resistance sequencing agents Methods: This ongoing, single arm, multicenter, Phase I, 3+3 design dose-escalation expansion study E+ evaluating safety, tolerability, PK, antitumor harboring FGFR3/2 who progressed platinum and/or inhibitor therapies. Dose escalation phase aims identify maximum tolerated dose (MTD) recommended 2 (RP2D) fixed E at 8 mg/day (table). Results: As data cutoff, 9 were enrolled completed limiting toxicity (DLT) period (1 st cycle) phase. Six DL1 1 DLT (skin rash) DL2 (no DLT). The most common all grade treatment-related adverse events (TRAEs) included hyperphosphatemia (88%), mucositis high AST hypercalcemia (75%), palmar plantar erythrodysesthesia peripheral neuropathy alopecia (63%), diarrhea hypoalbuminemia (63%) hypomagnesemia (63%). Grade TRAEs (50%), anemia (17%), rash anorexia (17%) paronychia (17%). One patient developed 4 Stevens-Johnson syndrome related which subsequently improved. PK available for 6 DL1. average steady-state Cmin MMAE was 1430 ± 639 ng/mL 1.4 0.9 ng/ml, respectively, Cmax 3.9 All evaluable 100% best objective rate, including partial responses (PRs) complete response (CR). mOS NR (95% 17.1 months-NR), mPFS 7.52 months CT 5.55-NR) median follow up 22.7 months. mDOR 5.49 RP2D 1.25 mg/kg mg/day. Conclusions: E+EV feasible preliminarily exhibits promising activity. ongoing E. Clinical trial information: NCT04963153 . Level (DL) Cycle Length -1 mg PO QD 0.75 IV (maximum 75 mg) D1,8,15 28 days 100 125