Infigratinib for the Treatment of Advanced or Metastatic Solid Tumors in Patients With FGFR Gene Mutations

Inclusion Criteria

• Patients with histologically or cytologically confirmed advanced or metastatic solid tumors of any histologic classification at the time of diagnosis
• Written documentation of local or central Clinical Laboratory Improvement Act (CLIA)-certified laboratory determination of FGFR gene fusions/translocations or activating mutations
• The study is open to solid tumors in the following cohorts:
• Cohort 1: Solid tumor patients with FGFR1-3 fusion/translocation (n=10) who have progressed on or are intolerant to standard of care (SOC) therapies and received treatment with a different FGFR inhibitor. Cholangiocarcinoma patients are permitted in this cohort
• Cohort 2: Solid tumor patients with FGFR1-3 fusion/translocation (n, up to 30) who have progressed on or are intolerant to SOC therapies. Prior therapy with a different FGFR inhibitor is not permitted. Cholangiocarcinoma patients are excluded from this cohort (there are multiple competing studies and opportunities for patients to get treatment in other trials)
• Cohort 3: Solid tumor patients with genetic alterations such as point mutations, insertions/deletions, or amplifications in any FGFR gene family member (n=10). Prior therapy with a different FGFR inhibitor is not permitted. Cholangiocarcinoma patients are permitted in this cohort
• Evidence of measurable or evaluable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Patients must have received at least one prior SOC regimen for advanced/metastatic cancer. Patient should have had evidence of progressive disease following their prior regimen, or if prior treatment was discontinued due to toxicity must have continued evidence of measurable or evaluable disease. Patients who have received prior treatment with an alternate FGFR inhibitor are still eligible for the study
• Patients with primary central nervous system (CNS) cancer or CNS metastases are excluded (because it is unclear how much CNS penetration the drug has). However, asymptomatic patients with history of successfully treated CNS metastases with surgery or radiation and follow up imaging showing stability, can be eligible
• Eastern Cooperative Oncology Group (ECOG) performance status = = 1.5 x upper limit of normal (ULN) unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) >= 3 x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
• Alkaline phosphatase >= 2.5 x ULN unless associated with patient's primary cancer and/or metastases and with principal investigator's approval
• Calculated or measured creatinine clearance of = 2), left ventricular ejection fraction (LVEF) 470 msec (males and females)
• History of congenital long QT syndrome
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 3 months following the discontinuation of study treatment. Highly effective contraception methods include:
• Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception
• Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment
• Male sterilization (at least 6 m