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

Sponsor

Blueprint Medicines Corporation (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02508467

Collaborator

(none)

150

Enrollment

Locations

Arm

Anticipated Duration (Months)

3.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma (HCC)	Drug: Fisogatinib (BLU-554)	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 31, 2015

Actual Primary Completion Date :

Jun 30, 2021

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Fisogatinib (BLU-554)

Fisogatinib (BLU-554) capsules for oral administration.

Drug: Fisogatinib (BLU-554)

Other Names:

BLU-554

Outcome Measures

Primary Outcome Measures

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

Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules [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 [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 [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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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