10011-CS-2 A Phase II basket trial evaluating the efficacy of tasurgratinib in patients with advanced solid tumors with fibroblast growth factor receptor (FGFR) gene alteration (FORTUNE study)

Abstract Background Tasurgratinib is orally available selective FGFR1-3 tyrosine kinase inhibitor approved in Japan for biliary tract cancer with FGFR2 fusions or rearrangements. We previously identified highly sensitive FGFR mutations to tasurgratinib using a high-throughput functional evaluation method (MANO method). We conducted a multicenter, single-arm investigator-initiated phase 2 basket trial to evaluate tasurgratinib in patients (pts) with FGFR alterations. Methods Pts with advanced solid tumors with FGFR gene alterations received tasurgratinib 140 mg QD. Pts were assigned to each group (Group A: FGFR1-3 fusion, Group B: FGFR1-3 mutation sensitive to tasurgratinib by MANO methods, Group C: FGFR1-3 activating mutation not in Group B or FGFR1/2 amplification, Group D: cholangiocarcinoma with FGFR2 fusion pretreated with other FGFR inhibitors). The primary endpoint for Groups A-C was objective response rate (ORR) by independent central review (ICR); Group D was exploratory cohort. Secondary endpoints included ORR by investigator assessment (IA), progression-free survival (PFS), overall survival, and safety. The threshold and expected response rates were 5% and 30%. Target enrollment for Group A, B, C and D were 10 pts, 15 pts, 15 pts and 1-5 pts, respectively. Results From June 2021 to December 2022, 46 pts enrolled and 41 comprised the full analysis set (A:10, B:15, C:15, D:1). Most common primary sites in each group were brain (A), biliary tract (B), and esophagus/stomach (C). ORRs by ICR were: A: 20.0% (90% CI 3.7-50.7, p = 0.0861), B: 20.0% (90% CI 5.7-44.0, p = 0.0362), and C: 6.7% (90% CI 0.3-27.9, p = 0.5367). ORRs by IA were: A: 20.0%, B: 40.0%, C: 13.3%, D: 0.0%. Median PFSs by IA were A: 2.5, B: 7.2, C: 2.2, D: 5.7 months. No new safety signals were observed. Conclusions Primary endpoint was met in Group B. Tasurgratinib demonstrated clinical activity in pts with selected FGFR-mutated tumors. Additional recruitment of pts has been resumed. (jRCT2031210043).