Clinical Trials

Inclusion Criteria:

• Provide written informed consent.
• Is ≥ 18 years (or according to the country's regulatory definition for legal adult age).
• Has histologically or cytologically confirmed, locally advanced, metastatic cancer meeting the following criteria:
• Phase 1 Expansion
  • Patient has failed (or, in the case of Group 2, failed or refused) all standard therapies or standard therapy does not exist or is not tolerated.
  •  Patient is eligible for 1 of the following enrollment groups, based on diagnosis, prior therapy, and FGF/FGFR aberrations as shown:
    • Group 1 (Enrollment Suspended as of Amendment 7): Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions.
    • Group 2: Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions, and has not received or received less than 1 cycle of prior chemotherapy (due to intolerance or patient refusal).
    • Group 3 (Enrollment Suspended as of Amendment 7): Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR2 gene fusions and has received prior treatment with FGFR inhibitors.
    • Group 4 (Enrollment suspended as of Amendment 7): Patient has intrahepatic or extrahepatic cholangiocarcinoma harboring FGFR abnormalities other than FGFR2 gene fusions (for example, mutations, rearrangements, or amplifications).
    • Group 5: Patient has a primary CNS tumor harboring FGFR gene fusion or FGFR1 activating mutation and fulfills the following criteria:
      • Patients who are presenting in recurrence or relapse must have at least one measurable enhancing mass lesion with 2 perpendicular diameters of at least 10 mm documented on baseline contrast magnetic resonance imaging (MRI) (gadolinium-based MRI);
      • Patients should be on a stable dose of steroids for at least 7 days prior to obtaining the baseline contrast MRI of the brain and at least 7 days prior to starting study drug.
    • Group 6 (Enrollment Suspended as of Amendment 7): Patient has advanced urothelial carcinoma harboring FGFR3 fusions or FGFR3 activating mutations.
    • Group 7: Patient has any tumor type not included in one of the prior groups, harboring FGFR2 amplification (no minimum number of copies).
    • Group 8 (Enrollment Suspended as of Amendment 7): Patient has any tumor type not included in one of the prior groups, harboring FGFR gene fusions or activating mutations.
• Phase 2
  • Patient has histologically or cytologically confirmed, locally advanced, metastatic, unresectable iCCA harboring FGFR2 gene fusions or other FGFR2 rearrangements based on results from either of the following:
    • Testing by Foundation Medicine:
      • As part of study pre-screening; or
      • Previously tested by Foundation Medicine; in this case, tumor tissue should be provided to Foundation Medicine, if available.
    • Local laboratory testing using next generation sequencing [NGS], fluorescence in situ hybridization [FISH], or other assays that can determine FGFR2 gene fusions or other FGFR2 rearrangements on tumor tissues or from ctDNA.  It is requested that patients enrolled on this basis provide tumor tissues to Foundation Medicine, if available from either archival samples or fresh tumor biopsy.
  • Patient has been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy. Patients with prior adjuvant gemcitabine-platinum chemotherapy are eligible if the patient had recurrence within 6 months of the last dose of the regimen.
  • Patient has documentation of radiographic disease progression on the most recent prior therapy.
• Patient has measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO criteria (2010) for brain tumors.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 on Day 1 of Cycle 1.
• Able to take medications orally (e.g., no feeding tube).
• Adequate organ function as defined by the following criteria:
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 ×upper limit of normal (ULN); if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤ 5 × ULN;
  • Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 mg/dL for patients with Gilbert’s syndrome;
  • International normalized ratio (INR) <1.3 (or < 3.0 on anticoagulants);
  • Absolute neutrophil count ≥1000/mm^3 (i.e., ≥ 1.0 × 10^9/L by International Units [IU]);
  • Platelet count ≥ 75,000/mm^3 (IU: ≥75 × 10^9/L);
  • Hemoglobin ≥ 9.0 g/dL;
  • Phosphorus ≤ ULN.
• Creatinine clearance (calculated* or measured value**): ≥ 40 mL/min
  • * For a calculated creatinine clearance (Ccr) value, the eligibility should be determined using the Cockcroft-Gault formula:
    • Male Ccr (mL/min) = Body weight (kg) × (140 – age)/[72 × creatinine (mg/dL)].
    • Female Ccr (mL/min) = male Ccr × 0.85.
  • **A measured Ccr value (i.e., not calculated) should meet this criterion.
• Women of child-bearing potential (WOCBP) must have a negative pregnancy test (urine or serum) within 7 days prior to administration of the first dose of TAS-120. Female patients are not considered to be of child-bearing potential if they have a history of hysterectomy or are post-menopausal defined as no menses for 12 months without an alternative medical cause. Both males and females of reproductive potential must agree to use effective birth control during the study prior to the first dose and for 6 months after the last dose.
• Willing and able to comply with scheduled visits and study procedures.

Exclusion Criteria:

• History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis.
• History and/or current evidence of clinically significant ectopic mineralization/calcification.
• History and/or current evidence of clinically significant retinal disorder confirmed by retinal examination.
• History or current evidence of serious uncontrolled ventricular arrhythmias
• Fridericia’s corrected QT interval (QTcF) > 470 ms on ECG conducted during Screening.
• Treatment with any of the following within the specified time frame prior to the first dose of TAS-120:
  • Major surgery within the previous 4 weeks (the surgical incision should be fully healed prior to the first dose of TAS-120);
  • Radiotherapy for extended field within 4 weeks or limited field radiotherapy within 2 weeks;
  • Patients with locoregional therapy; e.g., transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) or ablation within 4 weeks;
  • Any noninvestigational anticancer therapy within 3 weeks or have not recovered from side effects of such therapy prior to TAS-120 administration (mitomycin within prior 5 weeks);
    • Targeted therapy or immunotherapy within 3 weeks or within 5 half-lives (whichever is shorter).
  • Any investigational agent received within 5 half-lives of the drug or 4 weeks, whichever is shorter. Concurrent participation in an observational study may be allowed after review by the Sponsor’s Medical Monitor;
  • Patients with prior FGFR-directed therapy.
• A serious illness or medical condition(s) including, but not limited to, the following:
  • Known brain metastasis (not including primary brain tumors) unless patient is clinically stable for ≥ 1 month;
  • Known acute systemic infection;
  • Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure (New York Heart Association [NYHA] Class III or IV within the previous 2 months; if > 2 months, cardiac function must be within normal limits and the patient must be free of cardiac-related symptoms;
  • Chronic nausea, vomiting, or diarrhea considered to be clinically significant in the opinion of the investigator;
  • Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death;
  • Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the investigator would make the patient inappropriate for entry into this study.
• Patients with a history of another primary malignancy that is currently clinically significant, and has potential for metastases or currently requires active intervention (except for gonadotropin-releasing hormone (GnRH) or luteinizing hormone-releasing hormone (LH-RH) agonists in prostate cancer or adjuvant hormonal therapy in breast cancer).
• Pregnant or lactating female.