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

• ClinicalTrials.gov Identifier: NCT02508467
• Recruitment Status: Active, not recruiting
• First Posted: July 27, 2015
• Last Update Posted: February 3, 2021
• Sponsor: Blueprint Medicines Corporation
• Information provided by (Responsible Party): Blueprint Medicines Corporation

Tracking Information

• First Submitted Date: July 9, 2015
• First Posted Date: July 27, 2015
• Last Update Posted Date: February 3, 2021
• Study Start Date: July 2015
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 24, 2020)

• 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 ]
• Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules [ Time Frame: At the end of every cycle (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier ]
• Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings [ Time Frame: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study ]

Original Primary Outcome Measures (submitted: July 23, 2015)

• Maximum tolerated dose (MTD) [ Time Frame: During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier ]
• Recommended Phase 2 dose of BLU-554 [ Time Frame: At the end of every cycle (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier ]
• Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings [ Time Frame: Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study ]

Current Secondary Outcome Measures (submitted: January 24, 2020)

• Maximum plasma concentration of fisogatinib (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) ]
  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)
• Time to maximum plasma concentration of fisogatinib (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) ]
  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
• Fibroblast growth factor 19 (FGF19) status in tumor tissue [ Time Frame: Cycle 2 (Day 56) ]
• Levels of FGF19 in blood and tumor samples [ Time Frame: Cycle 1 (Day 28) ]
• Preliminary evidence of fisogatinib (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 ]

Original Secondary Outcome Measures (submitted: July 23, 2015)

• Maximum plasma concentration of BLU-554 [ 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) ]
  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)
• Time to maximum plasma concentration of BLU-554 [ 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) ]
  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
• Fibroblast growth factor 19 (FGF19) status in tumor tissue [ Time Frame: Cycle 2 (Day 56) ]
• Levels of cancer antigen (CA) 19-9 and FGF 19 in blood and tumor samples [ Time Frame: Cycle 1 (Day 28) ]
• Preliminary evidence of BLU-554 antineoplastic activity [ Time Frame: End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 1 Study of Fisogatinib (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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatocellular Carcinoma (HCC)

Intervention

Drug: Fisogatinib (BLU-554)

Other Name: BLU-554

Study Arms

Experimental: Fisogatinib (BLU-554)

Fisogatinib (BLU-554) capsules for oral administration.

Intervention: Drug: Fisogatinib (BLU-554)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: January 5, 2018): 150
• Original Estimated Enrollment (submitted: July 23, 2015): 60
• Estimated Study Completion Date: April 2021
• Estimated Primary Completion Date: April 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China, France, Germany, Hong Kong, Italy, Korea, Republic of, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02508467
• Other Study ID Numbers: BLU-554-1101; 2015-001662-26 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Blueprint Medicines Corporation
• Study Sponsor: Blueprint Medicines Corporation
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Blueprint Medicines Corporation
• Verification Date: February 2021