A Study of TAS-120 in Patients With Advanced Solid Tumors

Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

This is an open-label, nonrandomized, Phase 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts:

1. Dose escalation portion to determine the -Maximum Tolerated Dose and/ or Recommended Phase 2 Dose of futibatinib.
2. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary central nervous system tumors, urothelial carcinoma, breast cancer, gastric cancer.
3. Phase 2 study portion to confirm objective response rate of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).

Inclusion Criteria:

1. Provide written informed consent

2. Age ≥ 18 years of age

3. Has histologically or cytologically confirmed, locally advanced or metastatic cancer

4. The following specific criteria for each study portion

   Phase 1 (Dose Escalation):

   • Patients with any type of solid tumor
   • Disease progression following standard therapies or intolerant to prior standard therapies

   Phase 1 (Dose Expansion)

   • Have at least one FGF/FGFR aberration

   • Disease progression following standard therapies or were intolerant to prior standard therapies (including prior FGFR inhibitors).

   • Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or Response Assessment in Neuro-Oncology criteria (2010) for brain tumors.

   • Patients with any of the following tumor types

     • Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene fusions or other FGFR2 aberrations
     • Patients with primary CNS tumors
     • Patients with advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations
     • Patients with breast cancer or gastric cancer
     • Patients with other solid tumor types harboring FGFR gene fusions or activating mutations
     • Patients with solid tumor types and other FGF/FGFR alterations not listed above

   Phase 2

   • Patients with iCCA and FGFR2 gene rearrangements (incl fusions)
   • Have been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy
   • Must have documentation of radiographic progression of disease
   • No prior FGFR inhibitor
   • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009)

5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

6. Adequate organ function.

Exclusion Criteria:

1. History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis.
2. History and/or current evidence of clinically significant ectopic mineralization/calcification.
3. History and/or current evidence of clinically significant retinal disorder
4. A serious illness or medical condition(s)
5. Pregnant or breast-feeding female