A Phase 2 Study of Futibatinib Plus Pembrolizumab in Patients (pts) with Advanced or Metastatic Urothelial Carcinoma (Muc)

501 Background: Immune checkpoint inhibitors (ICIs), including pembrolizumab, are among the few treatment options available for platinum-ineligible pts with mUC, but only 25–30% of pts achieve responses with ICIs. FGFR DNA alterations (in 15–20% of mUCs) may contribute to poor responses to ICIs, and FGFR inhibition may sensitize tumors to ICIs by direct action on cancer cells or by altering the tumor microenvironment. In an open-label phase 2 study (NCT04601857), futibatinib, a highly selective, potent, irreversible FGFR1–4 inhibitor with activity in FGFR-deregulated tumors, is being assessed in combination with pembrolizumab in pts with mUC. Here, we report preliminary findings from the safety lead-in phase. Methods: Eligible pts (≥18 y; ECOG PS ≤1) had mUC, were treatment naive in the advanced/metastatic setting, and unfit for, intolerant to, or refusing platinum-based chemotherapy. Prior anti–PD-1/PD-ligand 1/2 or FGFR inhibitor therapy were not permitted. Pts (regardless of FGFR alteration status) were first enrolled in a safety lead-in and received futibatinib 20 mg orally once daily (QD) and pembrolizumab 200 mg IV every 21 d. Dose-limiting toxicities (DLTs) were assessed during the first 21-d treatment cycle. Results: As of September 27, 2021, 6 pts were enrolled in the safety lead-in. Median age was 73.5 y (range, 46–84 y) and 17% (1/6) of pts had an ECOG PS of 1. Median duration of treatment was 48 d (range, 21–141 d) with futibatinib and 35 d (1–114 d) with pembrolizumab. Two pts (33%) remained on treatment at data cutoff. Adverse events (AEs) were reported in all 6 pts; AEs in > 2 pts were diarrhea (83%), hyperphosphatemia (67%), increased aspartate aminotransferase (50%), and pruritis (50%). Grade 3 AEs were reported in 2/6 pts: increased aspartate aminotransferase, maculopapular rash, myositis (17% each). There were no grade 4–5 AEs. AEs led to any study drug discontinuation in 3 pts, dose interruption in 3 pts, and dose modification in 3 pts. All 6 pts were evaluated for DLTs after 1 treatment cycle; no DLTs were reported. Conclusions: Preliminary safety results support tolerability of futibatinib plus pembrolizumab in platinum-ineligible pts with mUC. As no DLTs were observed in the safety lead-in, the recommended dose of futibatinib in combination with pembrolizumab is 20 mg QD. Enrollment in pts with or without FGFR alterations is ongoing to evaluate antitumor activity by FGFR alteration status. Clinical trial information: NCT04601857.