Clinical Trials /

A Phase 1 Study of Fisogatinib (BLU-554) in Patients With Hepatocellular Carcinoma

NCT02508467

Description:

This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of fisogatinib (formerly known as BLU- 554) administered orally in patients with FGF19 IHC+ hepatocellular carcinoma (HCC). The study consists of 3 parts, a dose-escalation part (Part 1), an expansion part (Part 2) exploring a once daily (qd) dosing schedule at the recommended Phase 2 dose (RP2D), and a Part 3 expansion of the qd dosing schedule at the RP2D in TKI naive patients.

Related Conditions:
  • Hepatocellular Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase 1 Study of BLU-554 in Patients With Hepatocellular Carcinoma
  • Official Title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma

Clinical Trial IDs

  • ORG STUDY ID: BLU-554-1101
  • SECONDARY ID: 2015-001662-26
  • NCT ID: NCT02508467

Conditions

  • Hepatocellular Carcinoma (HCC)

Interventions

DrugSynonymsArms
BLU-554BLU-554

Purpose

This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of BLU- 554 administered orally in patients with FGF19 IHC+ hepatocellular carcinoma (HCC). The study consists of 3 parts, a dose-escalation part (Part 1), an expansion part (Part 2) exploring a once daily (qd) dosing schedule at the recommended Phase 2 dose (RP2D), and a Part 3 expansion of the qd dosing schedule at the RP2D in TKI naive patients.

Trial Arms

NameTypeDescriptionInterventions
BLU-554ExperimentalBLU-554 capsules for oral administration.
  • BLU-554

Eligibility Criteria

        Key Inclusion Criteria:

          -  Confirmed diagnosis of HCC by histological examination or by non-invasive criteria
             according to European Association for the Study of the Liver (EASL) or American
             Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3).

          -  For Part 1 and 2, the patient has unresectable disease and has been previously treated
             with sorafenib, has declined treatment with sorafenib, or does not have access to
             sorafenib.

          -  For Part 3, the patient has not received prior treatment with a TKI.

          -  Child-Pugh class A with no clinically apparent ascites

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

          -  For Part 1, willing to provide archived tumor tissue (if available) and willing to
             undergo pre- and on-treatment tumor biopsy (if considered safe and medically feasible
             by the treating investigator)

          -  For Part 2 and 3, all patients must have an FGF19 IHC result available. Only FGF19
             IHC+ HCC patients will be eligible for Part 3.

        Key Exclusion Criteria:

          -  Central nervous system metastases

          -  Platelet count <75,000/mL

          -  Absolute neutrophil count <1000/mL

          -  Hemoglobin <8 g/dL

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x the upper limit
             of normal (ULN)

          -  Total bilirubin >2.5 mg/dL

          -  International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds above
             control

          -  Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Maximum tolerated dose (MTD) on qd and bid schedules
Time Frame:During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Maximum plasma concentration of BLU-554 on qd and bid schedules
Time Frame:Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Safety Issue:
Description:Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT)
Measure:Time to maximum plasma concentration of BLU-554 on qd and bid schedules
Time Frame:Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Safety Issue:
Description:Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and EOT
Measure:Fibroblast growth factor 19 (FGF19) status in tumor tissue
Time Frame:Cycle 2 (Day 56)
Safety Issue:
Description:
Measure:Levels of FGF19 in blood and tumor samples
Time Frame:Cycle 1 (Day 28)
Safety Issue:
Description:
Measure:Preliminary evidence of BLU-554 antineoplastic activity
Time Frame:Screening, Day 1 of every odd numbered cycle starting with Cycle 3, End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Blueprint Medicines Corporation

Trial Keywords

  • Liver cancer
  • FGF19 gene amplification
  • FGF19 overexpression
  • FGF19 upregulation
  • Cyclin D1 (CCND1) gene amplification
  • Cyclin D1 (CCND1) copy number gain
  • BLU-554
  • FGFR4
  • Hepatocellular carcinoma
  • Liver Disease
  • Liver Neoplasms

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