Clinical Trials /

Efficacy and Safety of Pemigatinib in Previously Treated Locally Advanced/Metastatic or Surgically Unresectable Solid Tumor Malignancies Harboring Activating FGFR Mutations or Translocations

NCT03822117

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Efficacy and Safety of Pemigatinib in Previously Treated Locally Advanced/Metastatic or Surgically Unresectable Solid Tumor Malignancies Harboring Activating FGFR Mutations or Translocations
  • Official Title: A Phase 2, Open-Label, Single-Arm, Multicenter Study 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

Clinical Trial IDs

  • ORG STUDY ID: INCB 54828-207
  • NCT ID: NCT03822117

Conditions

  • Solid Tumor Malignancy

Interventions

DrugSynonymsArms
PemigatinibINCB054828Pemigatinib

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
PemigatinibExperimentalCohort A (Solid tumor malignancies with FGFR1-3 in frame fusions). Cohort B (Solid tumor malignancies with activating point mutations in FGFR1-3) Cohort C (Solid tumor malignancies with any other FGFR1-3 point mutations and variants of unknown significance).
  • Pemigatinib

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 < 12 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate (ORR) in Cohort A
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as the proportion of participants in Cohort A who achieve a complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Response Assessment in Neuro-Oncology (RANO) as determined by an independent radiological review committee.

Secondary Outcome Measures

Measure:Progression-free survival (PFS)
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as the time from first dose until progressive disease (according to RECIST v1.1 or RANO and assessed by an independent central review) or death (whichever is first) in Cohorts A and B, respectively.
Measure:Duration of response (DOR)
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as the time from the date of first assessment of CR or PR until the date of the first progressive disease (according to RECIST v1.1 or RANO and assessed by an independent central review) or death (whichever is first) in Cohorts A and B, respectively.
Measure:Overall survival (OS)
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as the time from first dose of study drug to death of any cause in Cohorts A and B, respectively.
Measure:Number of treatment-emergent adverse events
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Defined as adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Measure:Number of treatment-related adverse events.
Time Frame:Up to approximately 6 months
Safety Issue:
Description:Adverse events considered to be treatment-related by the investigator.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • Fibroblast growth factor receptor (FGFR) inhibitor
  • FGFR mutations
  • FGFR translocations
  • solid tumor malignancy

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