LBA27 Erdafitinib (ERDA) or ERDA Plus Cetrelimab (CET) for Patients with Metastatic or Locally Advanced Urothelial Carcinoma (muc) and Fibroblast Growth Factor Receptor Alterations (fgfra): First Phase (ph) II Results from the NORSE Study

First-line (1L) therapy for cisplatin (cis)-ineligible patients (pts) with mUC includes alternative chemotherapy or anti-PD-(L)1 monotherapy for PD-L1 positive tumors. The pan-FGFR inhibitor ERDA has established clinical benefit in 2L mUC for pts with targetable FGFRa. ERDA combined with the anti-PD-1 CET could expand 1L options for pts with FGFRa. The Ph 1b part of NORSE (NCT03473743) determined a tolerable dose of ERDA + CET in pts with 2L mUC. We report early results from the Ph 2 part of NORSE evaluating ERDA or ERDA + CET in cis-ineligible pts with 1L mUC and FGFRa. NORSE Ph 2 is enrolling pts ≥ 18 y with mUC, select FGFRa (mutation/fusion), and measurable disease (no prior systemic therapy for mUC, cis ineligible). Pts are randomized 1:1 to receive once-daily ERDA 8 mg (with pharmacodynamically guided uptitration [UpT] to 9 mg) or ERDA 8 mg (no UpT) + IV CET 240 mg every 2 wks at cycles 1-4 and 480 mg every 4 wks thereafter. Primary end points are investigator-assessed overall response rate (ORR) per RECIST 1.1 and safety; secondary include disease control rate (DCR), time to response (TTR), and duration of response (DOR). As of July 19, 2021, 53 pts were randomized; 26 to ERDA and 27 to ERDA + CET. For ERDA vs ERDA + CET: median age was 75 vs 69 y; visceral metastases were present in 54% vs 52%; ECOG was 0-1 in 77% vs 63%. Efficacy data in response-evaluable pts are shown in the table. The safety set comprised 24 pts who received ERDA and 24 who received ERDA + CET. The most frequent treatment-emergent adverse events were hyperphosphatemia (ERDA vs ERDA + CET, 58% vs 58%), stomatitis (63% vs 54%), and diarrhea (50% vs 42%).Table: LBA27Efficacy in response evaluable ptsERDA 8 mg with UpT (n = 18)ERDA 8 mg + CET (n = 19)ORR, % (95% CI)33 (13-59)68 (43-87)Confirmed CR, n14DCR, % (95% CI)100 (82-100)90 (67-99)Median DOR (95% CI), moNE (4.4-NE)6.9 (1.6-NE)Confirmed response ongoing, n/N5/610/13Median TTR, mo2.31.8 Open table in a new tab ERDA + CET showed clinically meaningful responses in cis-ineligible patients with 1L mUC and FGFRa. Safety was generally consistent with ERDA alone. Enrollment is ongoing.