A Phase Ib/II Study of Fisogatinib(BLU-554) in Subjects With Hepatocellular Carcinoma
A Muti-center, Open-label, Multiple-dose Phase Ib/II Study to Assess the Safety, Tolerability, Pharmacokinetics, Anti-tumor Efficacy of Fisogatinib(BLU-554) in Combination With CS1001 in Subjects With Locally Advanced or Metastatic Hepatocellular Carcinoma (HCC)
1 other identifier
interventional
26
1 country
3
Brief Summary
This study will evaluate the safety, tolerability, pharmacokinetic and efficacy of fisogatinib (formerly known as BLU-554) in combination with CS1001 in patients with locally advanced or metastatic hepatocellular carcinoma (HCC)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1 hepatocellular-carcinoma
Started Dec 2019
Shorter than P25 for phase_1 hepatocellular-carcinoma
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 10, 2019
CompletedFirst Posted
Study publicly available on registry
December 11, 2019
CompletedStudy Start
First participant enrolled
December 16, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 20, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
October 20, 2021
CompletedResults Posted
Study results publicly available
February 6, 2023
CompletedFebruary 6, 2023
December 1, 2022
1.8 years
December 10, 2019
October 19, 2022
January 10, 2023
Conditions
Outcome Measures
Primary Outcomes (3)
Phase Ib: Patients With Event(s) of Dose-limiting Toxicity
Number of DLT (Dose-limiting toxicity) During the Administration of BLU-554 in Combination with CS1001. All toxicity or adverse events (AEs) are graded according to NCI-CTCAE 5.0. Any AE occurring during C1 (21 days) that is not clearly caused by something other than investigational drug.
Cycle 1 (21 days) of treatment
Phase Ib: Safety and Tolerance
An AE was any untoward medical occurrence after clinical study subjects receive study drug. An SAE was any event that meets any the following criteria: death, life-threatening; inpatient hospitalization or prolongation, persistent or significant disability/incapacity;congenital malformation/birth defects and significant medical events. AE and SAE were graded by CTCAE version 5.0 by severity, from Grade 1 mild to Grade 5 death related AE.
Safety and tolerance assessments continued for the duration of treatment. AEs and SAEs will be collected from time of signature of main informed consent, throughout the treatment period and including the follow-up period, up to approximate 22 months.
Phase II: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1
Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1 .1) for target lesions and assessed by MRI/ CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \> =30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. Percentage of subjects who achieve objective tumor response (CR or PR) will be summarized.
Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Secondary Outcomes (20)
Disease Control Rate Assessed by Investigator
Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Duration of Response Assessed by Investigator
Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Phase Ib: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1
Imaging (CT or MRI) assessments per RECIST v1.1 will be performed within 28 days prior to the first dose (baseline assessment), every 9 weeks during the first year of the study, and every 12 weeks thereafter. Up to 22 months.
Patients With Anti-CS1001 Antibody
Pre-dose of Cycle 1, 2, 4, 5, 7, 10, 13, 16 and every 8 cycles thereafter. Up to 22 months.
Overall Survival
Subject should be followed from time of registration till the time of subject death. Up to 22 months.
- +15 more secondary outcomes
Study Arms (3)
Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg
EXPERIMENTALPhase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
EXPERIMENTALPhase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
EXPERIMENTALInterventions
Phase Ib: participants received 400 mg Fisogatinib (BLU-554) once daily (QD), in combination with 1200mg fixed dose Sugemalimab (CS1001) once every 3 weeks (Q3W). Every 21 days (3 weeks) will be considered as one cycle.
Phase Ib: participants received 600 mg Fisogatinib (BLU-554) QD, in combination with 1200mg fixed dose Sugemalimab (CS1001) Q3W. Every 21 days (3 weeks) will be considered as one cycle.
Phase II: participants received 600 mg Fisogatinib (BLU-554) QD, in combination with 1200mg fixed dose Sugemalimab (CS1001) Q3W. Every 21 days (3 weeks) will be considered as one cycle.
Eligibility Criteria
You may qualify if:
- Voluntarily participate in the clinical study. Fully understand and get informed of this study and sign the Informed Consent Form (ICF).
- ≥18 years of age on day of signing the informed consent.
- Unresectable locally advanced or metastatic hepatocellular carcinoma as confirmed by histology or cytology.
- Stage B or C based on Barcelona Clinic Liver Cancer (BCLC) staging system; In case of Stage B, subject must be ineligible for surgery and/or local therapy, or has progressed after surgery and/or local therapy or refuses surgery and/or local treatment.
- For Phase Ib, subject has failed after or is unsuitable for the standard systemic therapy against HCC. For Phase II, subject has not previously received systemic therapy.
- At least one measurable lesion as evaluable by RECIST version 1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 point.
- A-level Child-Pugh score.
- Expected survival≥3 months.
- For Phase Ib and II, fresh or archived tumor tissue should be provided for analysis in the central laboratory.
- The function of the main organs was basically normal and met the requirements of the protocol.
- For subject with HCV infection, HCV antiviral treatment with the locally approved and available HCV antiviral therapy can be received.
- For subjects with HBV infection, HBV DNA ≤ 2,000 IU/ml at Screening.
- For female subjects of childbearing potential, serum pregnancy test must be negative within 7 days prior to randomization. Except for female subjects who have been recorded as surgically sterilized or who are postmenopausal, female subjects of childbearing potential or male subjects and their partners must agree to use effective contraception from the signature of the informed consent form (ICF) until at least 6 months after the last dose of study drug.
You may not qualify if:
- tumor thrombus in the main portal vein (VP4) by imaging, involving the inferior vena cava or the heart.
- Prior history of hepatic encephalopathy.
- History of liver surgery and/or local treatment for HCC (intervention, ablation therapy, absolute alcohol injection, etc.) or radiotherapy, etc. within 4 weeks prior to first dose.
- Active or documented gastrointestinal bleeding within 6 months (e.g. esophageal or gastric varices, ulcer bleeding).
- Presence of ascites detected by physical examination or clinical symptoms caused by ascites during the screening period, or ascites that need for special treatment, such as repeated drainage, intraperitoneal drug infusion, etc.
- Presence of meningeal metastasis or central nervous system (CNS) metastatic lesions.
- Subject has clinically significant, uncontrolled cardiovascular disease.
- History of definite interstitial lung disease or non-infectious pneumonia except that caused by local radiotherapy; history of active tuberculosis.
- Any serious acute, chronic infections that require systemic antimicrobial, antifungal or antiviral therapy at screening, excluding viral hepatitis.
- Malabsorption syndrome or inability to take the study drug orally for other reasons.
- Had primary malignancies other than HCC within 5 years.
- Subject has had major surgery within 4 weeks prior to first dose (procedures such as central venous cannulation, biopsy, and feeding tube placement are not considered as major surgery).
- Previously received FGFR4 inhibitor treatment.
- Blood transfusion, use of hematopoietic stimulating factors \[including G-CSF (granulocyte colony stimulating factor), GM-CSF (granulocyte-macrophage colony stimulating factor), EPO (erythropoietin) and TPO (thrombopoietin)\] and human albumin preparations within 14 days prior to first dose.
- Requiring corticosteroids (dose equivalent to \> 10 mg/day of Prednisone) or other immunosuppressive drugs within 14 days prior to first dose for systemic therapy.
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- CStone Pharmaceuticalslead
- Blueprint Medicines Corporationcollaborator
Study Sites (3)
Nanfang Hospital,
Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081, China
Shanghai East Hospital
Shanghai, Shanghai Municipality, 201203, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Hua Hu
- Organization
- CStone Pharmaceuticals
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 10, 2019
First Posted
December 11, 2019
Study Start
December 16, 2019
Primary Completion
October 20, 2021
Study Completion
October 20, 2021
Last Updated
February 6, 2023
Results First Posted
February 6, 2023
Record last verified: 2022-12