Hepatocellular CarcinomaPhase 1/2NCT04194801
A Phase Ib/II Study of Fisogatinib(BLU-554) in Subjects With Hepatocellular Carcinoma
A Phase 1/2 study testing Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg, Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg and Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg in people with Hepatocellular Carcinoma, run by CStone Pharmaceuticals at 3 sites in China.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg, Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg and Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesChina
- Study dates
- 16 Dec 2019to 20 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Use of traditional Chinese medicine with anti-liver cancer indication within 14 days prior to the first dose.
- Subject has received potent CYP3A4 inhibitors and/or inducers within 2 weeks prior to first dose.
- Concurrent HBV and HCV infection.
- Subjects with known human immunodeficiency virus (HIV) infection.
- Lactating women.
- Subjects with a history of hypersensitivity or hypersensitivity to any of the components of the investigational drug.
- Circumstances that in the opinion of the investigator would preclude participation in the study.
- Subjects who are unwilling or unable to follow the study procedures as defined.
- With the exception of alopecia, all toxicities from prior anticancer therapies and other therapies did not recover to ≤ Grade 1 (per CTCAE v5.0) prior to the first dose of study drug.
- Subjects who have received prior allogeneic stem cell or solid organ transplantation.
Trial locations and contacts
3 sites in 1 country.
China3 sites
Nanfang Hospital,
Guangzhou, Guangdong
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081
Shanghai East Hospital
Shanghai, Shanghai Municipality, 201203
About this study
Official title: 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)
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)
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg, Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg, Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mgDrug
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: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mgDrug
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: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg | Experimental | Not described Receives: Drug: Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg |
| Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg | Experimental | Not described Receives: Drug: Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg |
| Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg | Experimental | Not described Receives: Drug: Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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
Disease control rate (DCR) is defined as the proportion of participants who achieve complete response (CR), partial response (PR), and stable disease (SD) based on Response Evaluation Criteria In Solid Tumors (RECIST)v1.1. 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. Stable disease(SD) is defined as a tumor that does not meet the criteria for progression or for response.
Measured: 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
Duration of response for responders (CR or PR) is defined as the time interval between the date of the earliest qualifying response and the date of PD or death for any cause (whichever occurs earlier). For subjects who are alive without progression following the qualifying response, duration of response will be censored on the date of last evaluable tumor assessment or last follow-up for progression of disease.
Measured: 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
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.
Measured: 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
Measured: Pre-dose of Cycle 1, 2, 4, 5, 7, 10, 13, 16 and every 8 cycles thereafter. Up to 22 months.
Overall Survival
Overall survival is defined as the time interval between the date of the first investigational product dose to the date of death from any cause
Measured: Subject should be followed from time of registration till the time of subject death. Up to 22 months.
Disease Control Rate by PD-L1 Protein Level
Measured: Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level 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.
Objective Response Rate (ORR) by PD-L1 Protein Level
Measured: Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level 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.
Progression-free Survival Assessed by Investigator
Progression-free Survival is defined as the time from the date of first study dose to disease progression or death (whichever occurs first).
Measured: 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.
Time to Progression Assessed by Investigator
Time to Progression is defined as the time from the date of first study dose to disease progression. Subjects without event (no disease progression) will be censored at the date of "last tumor assessment".
Measured: 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 II: 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.
Measured: 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.
Pharmacokinetic Parameters of Accumulation Ratio of Fisogatinib (BLU-554)
Pharmacokinetic(PK) parameters of accumulation ratio of Fisogatinib (BLU-554),Rac,AUC. Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC) of Fisogatinib (BLU-554)
Pharmacokinetic parameters of area under the serum concentration-time curve (AUC0-τ,ss, Time from 0 to 24h) of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Fisogatinib (BLU-554)
Pharmacokinetic Parameters of Clearance at Steady State (Clss) of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Fisogatinib (BLU-554)
PK Parameters of Cmax of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Fisogatinib (BLU-554)
PK Parameters of Tmax of Fisogatinib (BLU-554). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Accumulation Ratio of Sugemalimab (CS1001)
PK Parameters of Rac, AUC of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC ) of Sugemalimab (CS1001)
PK Parameters of (AUC 0-τ,ss ) of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Sugemalimab (CS1001)
PK Parameters of CLss of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Sugemalimab (CS1001)
PK Parameters of Cmax of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Sugemalimab (CS1001)
PK Parameters of Tmax of Sugemalimab (CS1001). Only participants with evaluable PK results were included in the analysis. Where data is not presented, the PK profiles were non-measurable. Results for Phase Ib and Phase II have been pooled for the same dosage.
Measured: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2019
- Study start16 Dec 2019
- Primary completion20 Oct 2021
- Study completion20 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- CStone Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Blueprint Medicines Corporation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04194801
- Sponsor's protocol ID
- CS3008-101
- Status last verified
- Dec 2022
- First submitted
- 10 Dec 2019
- Last updated
- 6 Feb 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04194801
- Acronym / sponsor ID
- CS3008-101
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- CStone PharmaceuticalsIndustry (pharma, biotech, devices)
- Collaborators
- Blueprint Medicines Corporation
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- 20 Oct 2021 (actual)
- Study completion
- 20 Oct 2021 (actual)
- First posted
- 11 Dec 2019 (actual)
- Results
- Posted 6 Feb 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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)
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg | Experimental | Drug: Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg |
| Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg | Experimental | Drug: Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg |
| Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg | Experimental | Drug: Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mgPhase 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. | Drug | Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg |
| Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mgPhase 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. | Drug | Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg |
| Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mgPhase 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. | Drug | Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg |
Primary outcome
Phase Ib: Patients With Event(s) of Dose-limiting Toxicity
Time frame: Cycle 1 (21 days) of treatment
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.
Phase Ib: Safety and Tolerance
Time frame: 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.
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.
Phase II: Objective Response Rate (ORR) Assessed by Investigator Based on RECIST Version 1.1
Time frame: 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.
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.
20 secondary outcomes
Disease Control Rate Assessed by Investigator
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Pre-dose of Cycle 1, 2, 4, 5, 7, 10, 13, 16 and every 8 cycles thereafter. Up to 22 months.
Overall Survival
Time frame: Subject should be followed from time of registration till the time of subject death. Up to 22 months.
Disease Control Rate by PD-L1 Protein Level
Time frame: Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level 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.
Objective Response Rate (ORR) by PD-L1 Protein Level
Time frame: Imaging (CT or MRI) assessments by FGF19 protein and PD-L1 protein level 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.
Progression-free Survival Assessed by Investigator
Time frame: 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.
Time to Progression Assessed by Investigator
Time frame: 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 II: Safety and Tolerance
Time frame: 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.
Pharmacokinetic Parameters of Accumulation Ratio of Fisogatinib (BLU-554)
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC) of Fisogatinib (BLU-554)
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Fisogatinib (BLU-554)
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Fisogatinib (BLU-554)
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Fisogatinib (BLU-554)
Time frame: For BLU554, Cycle 1 day 1( 0, 0.5 to 24 hour post dose) and Cycle 2 day 1( 0, 0.5 to 24 hour post dose).
Pharmacokinetic Parameters of Accumulation Ratio of Sugemalimab (CS1001)
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Area Under the Serum Concentration-time Curve (AUC ) of Sugemalimab (CS1001)
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Clearance at Steady State (CLss) of Sugemalimab (CS1001)
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Maximum Serum Concentration (Cmax) of Sugemalimab (CS1001)
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Pharmacokinetic Parameters of Time to Maximum Serum Concentration (Tmax) of Sugemalimab (CS1001)
Time frame: For CS1001: Cycle 1 day 1(0, 0.5 to 504 hour post dose) and Cycle 4 day 1 (0, 0.5 to 504 hour post dose).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Phase Ib: Fisogatinib (BLU-554) 400mg in combination with Sugemalimab (CS1001) 1200mg, Phase Ib: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg and Phase II: Fisogatinib (BLU-554) 600mg in combination with Sugemalimab (CS1001) 1200mg in people with Hepatocellular Carcinoma, run by CStone Pharmaceuticals at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Feb 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase Ib: Patients With Event(s) of Dose-limiting Toxicity (time frame: Cycle 1 (21 days) of treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Feb 2023.