Efficacy and safety of fexagratinib (Fexa) in Chinese patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) harboring FGF receptor (FGFR) genetic alterations.

790 Background: Fexagratinib (former AZD4547), a selective and potent oral inhibitor of FGFR1-3, has shown promising efficacy and safety in phase I trials among solid tumor pts with FGFR1-3 alterations, including mUC. This study (NCT05086666) aimed to assess efficacy and safety of Fexa in previously treated Chinese mUC pts with FGFR alterations. Methods: Pts with mUC harboring FGFR3 alterations (including activating mutations or fusion detected via NGS panel) who failed at least 1 prior therapy or were platinum- ineligible, were enrolled. Pts received continuous oral Fexa 80mg BID until disease progression or unacceptable toxicity occurred. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST v1.1. Results: As of data cutoff (14 Jun 2024), a total of 35 pts were enrolled, of those 80% were male with a median age of 66 years (range 41-86). Most pts (85.7%) had ECOG PS≤1, 43% had a creatinine clearance <60 mL/min, 66% had received ≥ 1 prior therapies, 66% had been treated with PD-(L)1. The primary tumor site was reported in the upper tract in 40% of pts, and 25.7% had liver metastases. The best overall responses assessed by IRC was 34.4% (95% CI, 18.6%-53.2%) in 32 evaluable pts, including 9 confirmed partial responses (cPRs), 2 unconfirmed PRs. Ten (37.0%) of 27 evaluable pts harboring FGFR3 mutation achieved at least one PR. Among 15 pts who experienced progression after PD-(L)1 treatment, 5 pts (33.3%) achieved cPRs. Median PFS by IRC was 3.6 (2.8, 6.1) months. Most common treatment-related adverse events (TRAEs) were anemia (40.0%), nail disorder (40.0%), hyperphosphatemia (37.1%) and hyponatremia (34.3%). Grade ≥3 TRAEs were reported in 54.3% of the pts, incidence >5% included pneumonia(5.7%), anemia (5.7%) and hand-foot syndrome (5.7%). Conclusions: Fexa was generally well tolerated in previously treated Chinese mUC pts, with no new safety signals identified. The efficacy observed was consistent with that previously reported in western populations, with notable benefits seen in pts with FGFR alterations who had experienced disease progression following PD-(L)1 treatment. Clinical trial information: NCT05086666 .