Phase 2 study of futibatinib in combination with pembrolizumab in patients with FGF19 expressing advanced hepatocellular carcinoma

Abstract

Abstract Introduction Optimal treatment following first-line immunotherapy for advanced hepatocellular carcinoma (HCC) remains uncertain. This study evaluated futibatinib, a pan-FGFR inhibitor, combined with pembrolizumab in previously treated patients with FGF19-expressing HCC. Methods Eligible patients were ≥18 years old with advanced HCC, prior systemic therapy, Child-Pugh A-B7 liver function, ECOG 0-2, and FGF19 overexpression. Patients received futibatinib 20 mg orally daily plus pembrolizumab 200 mg intravenously every 3 weeks. The primary endpoint was progression-free survival at 6 months (PFS6). Secondary endpoints included overall survival (OS), objective response rate (ORR), quality of life, and safety. Results Between August 2021 and March 2024, 14 patients enrolled and 13 were evaluable. Median age was 72 years (range, 60-87), 53.8% were male, 92.3% had Child-Pugh A liver function, and all had received prior immunotherapy. Median progression-free survival was 15 weeks (95% CI, 9.0-NE), with a PFS6 rate of 23.1% (95% CI, 8.6-62.3%). ORR was 0% (95% CI, 0-24.7%), while stable disease was observed in 53.9% of patients. Median OS was 55.7 weeks (95% CI, 47.3-NE). Grade ≥3 adverse events occurred in 69.2% of patients, and grade ≥4 adverse events in 15.4%. One grade 5 event (acute-on-chronic kidney injury) was deemed unrelated to treatment. Common adverse events included hyperphosphatemia, fatigue, diarrhea, elevated transaminases, dry eye, nail changes, rash, and oral mucositis. Conclusions Futibatinib plus pembrolizumab demonstrated an acceptable safety profile but did not meet efficacy thresholds supporting further study in FGF19-expressing HCC. Effective post-immunotherapy treatment strategies remain an unmet need.