A phase II basket trial evaluating the efficacy of tasurgratinib (E7090) in patients with advanced solid tumors with fibroblast growth factor receptor (FGFR) gene alteration: FORTUNE study.

Abstract

3147 Background: Tasurgratinib is an orally available selective inhibitor of FGFR1-3 tyrosine kinase and is approved in Japan for biliary tract cancer with FGFR2 fusions or rearrangements based on a global phase 2 study. We previously identified FGFR gene alterations that are highly sensitive to tasurgratinib using a high-throughput functional evaluation method (MANO method) (npj Precision Oncology [2021] 5:66). We conducted a single-arm, investigator-initiated multicenter phase 2 basket trial to evaluate the efficacy and safety of tasurgratinib in patients (pts) with advanced solid tumors harboring FGFR gene alterations, including alterations identified by MANO method. Methods: Pts with advanced solid tumors with FGFR gene alterations detected by next-generation sequencing assays received tasurgratinib 140 mg QD. Pts were allocated to each Group based on FGFR gene alteration (Group A: FGFR1-3 fusion, Group B: FGFR1-3 sensitive mutations to tasurgratinib determined by MANO methods, Group C: FGFR1-3 activating mutation not applicable to group B or FGFR1, 2 gene amplification, Group D: cholangiocarcinoma with FGFR2 fusion and previous treatment with a FGFR inhibitor except for tasurgratinib). The primary endpoint for Groups A, B, and C was objective response rate (ORR) by independent central review (ICR). Group D was an exploratory cohort, and ICR was not performed. The 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%, respectively. With the one-sided significance level of 5%, the target enrolments were 10 (62% power), 15 (87%), and 15 pts (87%) in Groups A, B, and C, respectively. Group D's target number was 1 to 5 pts without a statistical hypothesis. Results: From June 2021 to December 2022, 46 pts were registered. The full analysis set includes 41 pts (10, 15, 15, and 1 in Groups A, B, C, and D, respectively). The most common primary sites were brain in 4 pts (40.0%) in Group A, biliary tract in 4 pts (26.7%) in Group B, and esophagus/stomach in 4 pts (26.7%) in Group C. ORRs by ICR in Group A, B and C were 20.0% (90% CI: 3.7-50.7, p = 0.0861), 20.0% (90% CI: 5.7-44.0, p = 0.0362), 6.7% (90% CI: 0.3-27.9, p = 0.5367), respectively. ORRs by IA in Group A, B, C, and D were 20.0% (95% CI: 2.5-55.6), 40.0% (95% CI: 16.3-67.7), 13.3% (95% CI: 1.7-40.5) and 0.0% (95% CI: 0.0-97.5), respectively. Median PFS by IA in Groups A, B, C, and D were 2.5 (95% CI: 1.4-5.7), 7.2 (95% CI: 1.7-8.2), 2.2 (95% CI: 1.9-3.7) and 5.7 months (95% CI: not evaluable), respectively. There was no new safety signal compared to previous reports. Conclusions: In Group B, the primary endpoint was met. Tasurgratinib demonstrated clinical activity in pts with selected FGFR-mutated tumors. Further study is needed to validate these findings. Clinical trial information: NCT04962867 .