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

Hepatocellular Carcinoma (HCC) Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT02508467
• Other study ID #: BLU-554-1101
• Secondary ID: 2015-001662-26
• Status: Completed
• Phase: Phase 1
• Start date: July 31, 2015
• Est. completion date: February 28, 2024

Study information

• Verified date: March 2024
• Source: Blueprint Medicines Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: February 28, 2024
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma (HCC)

Intervention

Drug:
• Fisogatinib (BLU-554)

Locations

Country	Name	City	State
China	Jilin Cancer Hospital	Changchun	Jilin
China	Jilin University the First Affiliated Hospital	Changchun	Jilin
China	Hunan Cancer Hospital, Radioactive Interventional Department	Changsha	Hunan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Nanfang Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital, College of Medicine, Zhejiang University	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital	Hangzhou	Gongshu District
China	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang
China	The Chinese People's Liberation Army 81 Hospital	Nanjing	Jiangsu
China	Nantong Tumor Hospital	Nantong	Jiangsu
China	Fudan University Shanghai Cancer Center	Shanghai	Xuhui District
China	Tianjin Medical University Cancer Institute & Hospital, Hepatobiliary Oncology Department	Tianjin	West Lake District
China	Fudan University Zhongshan Hospital	Xuhui	Shanghai City
China	Henan Cancer Hospital	Zhengzhou	Henan
France	Hospital Beaujon	Clichy
France	Institut Gustave Roussy	Villejuif
Germany	University of Frankfurt	Frankfurt
Germany	Johannes Gutenberg University Mainz - University Medical Center	Mainz	Rhineland-Palatine
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Italy	IRCCS Foundation - National Institute of Tumors	Milan
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Singapore	National Cancer Centre	Singapore
Spain	Vall d'Hebron Institute of Oncology	Barcelona
Switzerland	Inselspital Bern	Bern
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei
United Kingdom	University of Liverpool - Clatterbridge Cancer Centre	Bebington
United Kingdom	Guy's Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	University College London	London
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Miami - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Ochsner Cancer Institute	New Orleans	Louisiana
United States	Mount Sinai Medical Center	New York	New York
United States	Inland Empire Liver Foundation	Rialto	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	H. Lee Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Blueprint Medicines Corporation

Countries where clinical trial is conducted

United States,  China,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Singapore,  Spain,  Switzerland,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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)
Secondary	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)
Secondary	Fibroblast growth factor 19 (FGF19) status in tumor tissue		Cycle 2 (Day 56)
Secondary	Levels of FGF19 in blood and tumor samples		Cycle 1 (Day 28)
Secondary	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