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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Fisogatinib (BLU-554)

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Gongshu District
    • Hangzhou, Gongshu District, China, 310022
      • Zhejiang Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510445
      • Nanfang Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Harbin medical university cancer hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital, Radioactive Interventional Department
  • Jiangsu
    • Nanjing, Jiangsu, China, 210002
      • The Chinese People's Liberation Army 81 Hospital
    • Nantong, Jiangsu, China, 226361
      • Nantong Tumor Hospital
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital
    • Changchun, Jilin, China, 130021
      • Jilin University the First Affiliated Hospital
  • Shanghai City
    • Xuhui, Shanghai City, China, 200032
      • Fudan University Zhongshan Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • West Lake District
    • Tianjin, West Lake District, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital, Hepatobiliary Oncology Department
  • Xuhui District
    • Shanghai, Xuhui District, China, 200032
      • Fudan University Shanghai Cancer Center
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital, College of Medicine, Zhejiang University
• France
  • Clichy, France, 92110
    • Hospital Beaujon
  • Villejuif, France, 94805
    • Institut Gustave Roussy
• Germany
  • Frankfurt, Germany, 60590
    • University of Frankfurt
  • Rhineland-Palatine
    • Mainz, Rhineland-Palatine, Germany, 55131
      • Johannes Gutenberg University Mainz - University Medical Center
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Hong Kong, Hong Kong
    • Prince of Wales Hospital
• Italy
  • Milan, Italy, 21033
    • IRCCS Foundation - National Institute of Tumors
• Korea, Republic of
  • Gyeonggi-do, Korea, Republic of, 10408
    • National Cancer Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
• Spain
  • Barcelona, Spain, 08035
    • Vall d'Hebron Institute of Oncology
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Bern
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• United Kingdom
  • Bebington, United Kingdom, CH63 4JY
    • University of Liverpool - Clatterbridge Cancer Centre
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, SE1 9RY
    • Guy's Hospital
  • London, United Kingdom, W1T 7HA
    • University College London
• United States
  • California
    • Rialto, California, United States, 92377
      • Inland Empire Liver Foundation
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami - Sylvester Comprehensive Cancer Center
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02144
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fisogatinib (BLU-554); Fisogatinib (BLU-554) capsules for oral administration.	Drug: Fisogatinib (BLU-554); Other Names: BLU-554

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD) on qd and bid schedules	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	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	Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules	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)	Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules	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	Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study)
Fibroblast growth factor 19 (FGF19) status in tumor tissue		Cycle 2 (Day 56)
Levels of FGF19 in blood and tumor samples		Cycle 1 (Day 28)
Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity		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

Collaborators and Investigators

• Sponsor: Blueprint Medicines Corporation

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2015
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): February 28, 2024

Study Registration Dates

• First Submitted: July 9, 2015
• First Submitted That Met QC Criteria: July 23, 2015
• First Posted (Estimated): July 27, 2015

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Liver Disease; Hepatocellular carcinoma; Liver cancer; Liver Neoplasms; FGFR4; FGF19 gene amplification; FGF19 overexpression; FGF19 upregulation; Cyclin D1 (CCND1) gene amplification; Cyclin D1 (CCND1) copy number gain; BLU-554
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Antineoplastic Agents; Fisogatinib
• Other Study ID Numbers: BLU-554-1101; 2015-001662-26 (EudraCT Number)