Efficacy and Safety of Pemigatinib in Previously Treated Locally Advanced/Metastatic or Surgically Unresectable Solid Tumor Malignancies Harboring Activating FGFR Mutations or Translocations (FIGHT-207)
Condition: Solid Tumor Malignancy
MeSH terms: Neoplasms
Intervention: Pemigatinib
Intervention description: Pemigatinib administered orally once daily (QD).
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This study consists of 3 cohorts that will have study drug administered in parallel, Cohort A, Cohort B, and Cohort C. There is no difference in the treatment regimen between the cohorts.
Masking: None (Open Label)
Enrollment: 111.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Fibroblast growth factor receptor (FGFR) inhibitor; FGFR mutations; FGFR translocations; solid tumor malignancy

Summary:

      The purpose of this study is to evaluate the efficacy and safety of pemigatinib in
      participants with previously treated locally advanced/metastatic or surgically unresectable
      solid tumor malignancies harboring activating FGFR mutations or translocations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed solid tumor malignancy that is advanced or
             metastatic or is surgically unresectable.

          -  Radiographically measurable disease (per RECIST v1.1 or RANO for primary brain
             tumors). Tumor lesions located in a previously irradiated area or in an area subjected
             to other loco-regional therapy are considered measureable if progression has been
             clearly demonstrated in the lesion.

          -  Documentation of an FGFR1-3 gene mutation or translocation.

          -  Objective progression after at least 1 prior therapy and no therapy available that is
             likely to provide clinical benefit. Participants who are intolerant to or decline the
             approved therapy are eligible only if they have no therapy available that is likely to
             provide clinical benefit.

          -  Eastern Cooperative Oncology Group performance status 0 to 2.

          -  Baseline archival tumor specimen (if less than 24 months from date of screening) or
             willingness to undergo a pretreatment tumor biopsy to obtain the specimen. Must be a
             tumor block or approximately 15 unstained slides from biopsy or resection of primary
             tumor or metastasis.

          -  Willingness to avoid pregnancy or fathering children.

        Exclusion Criteria:

          -  Prior receipt of a selective FGFR inhibitor in the past 6 months.

          -  Receipt of anticancer medications or investigational drugs for any indication or
             reason within 28 days before first dose of pemigatinib.

          -  Cannot be a candidate for potentially curative surgery.

          -  Current evidence of clinically significant corneal or retinal disorder as confirmed by
             ophthalmologic examination.

          -  Radiation therapy administered within 2 weeks of enrollment/first dose of study
             treatment.

          -  Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases
             that have progressed (eg, evidence of new or enlarging brain metastasis or new
             neurological symptoms attributable to brain or CNS metastases).

          -  Known additional malignancy that is progressing or requires active treatment.

          -  History of calcium and phosphate hemostasis disorder or systemic mineral imbalance
             with ectopic calcification of soft tissues.

          -  Clinically significant or uncontrolled cardiac disease.

          -  Active chronic or current infectious disease requiring systemic antibiotic,
             antifungal, or antiviral treatment within 2 weeks before enrollment (participants with
             asymptomatic chronic infections on prophylactic treatment are allowed).

          -  Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
             (defined as elevated transaminases or cirrhosis; chronic HBV/HCV infection with no
             cirrhosis and no elevated transaminases is allowed).

          -  Known HIV infection.

          -  Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14
             days or five half-lives (whichever is longer) before the first dose of study
             drug/treatment.

          -  Women who are pregnant or breastfeeding.