a study of tas-120 in patients with advanced solid tumors

Conditions: Cholangiocarcinoma; Urothelial Cancer; Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors; Primary CNS Tumors; Breast Cancer; Gastric Cancer

Summary: 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).


Eligibility criteria:
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

Keywords: fgf fgfr futibatinib tas-120