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A First-in-Human, Phase 1 Study of SY-4798 in Patients With Advanced Solid Tumor

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05498519
Recruitment Status : Recruiting
First Posted : August 12, 2022
Last Update Posted : August 12, 2022
Sponsor:
Information provided by (Responsible Party):
Shouyao Holdings (Beijing) Co. LTD

Tracking Information
First Submitted Date  ICMJE August 10, 2022
First Posted Date  ICMJE August 12, 2022
Last Update Posted Date August 12, 2022
Actual Study Start Date  ICMJE April 15, 2021
Estimated Primary Completion Date April 15, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 10, 2022)
  • Incidence of dose limiting toxicities (DLTs) [ Time Frame: Escalation Cycle 1 (28 days) ]
    Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) in Cycle 1.
  • Incidence of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 24 months ]
    Characterization of the safety and tolerability as determined by changes in laboratory values and electrocardiograms.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 10, 2022)
  • Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria [ Time Frame: Up to 24 months ]
    Preliminary measure of anti-tumor activity of SY-4798 in patients with FGF19+ advanced tumor.
  • Duration of response (DOR) [ Time Frame: Up to 24 months ]
    Preliminary measure of anti-tumor activity of SY-4798 in patients with FGF19+ advanced tumor.
  • Pharmacokinetics (Cmax) for SY-4798 [ Time Frame: Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days) ]
    Defined as maximum observed plasma concentration
  • Pharmacokinetics (Tmax) for SY-4798 [ Time Frame: Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days) ]
    Defined as time to maximum plasma concentration
  • Pharmacokinetics (AUC0-t) for SY-4798 [ Time Frame: Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days) ]
    Defined as area under the single-dose plasma concentration-time curve from Hour 0 to the last quantifiable measurable plasma concentration
  • Pharmacokinetics (t½) for SY-4798 [ Time Frame: Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days) ]
    Defined as the apparent plasma terminal phase disposition half-life
  • Pharmacokinetics (Cl/F) for SY-4798 [ Time Frame: Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days) ]
    Defined as oral dose clearance
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A First-in-Human, Phase 1 Study of SY-4798 in Patients With Advanced Solid Tumor
Official Title  ICMJE A Phase I, Open-Label, Multi-Center, Dose-escalation/ Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Anti-Tumor Activity of SY-4798 Tablet in Patients With Advanced Solid Tumor
Brief Summary This is a Phase 1, open-label and multicenter study of SY-4798, a highly specific and potent inhibitor of FGFR4, in patients with advanced solid tumor. This study has two phases: dose-escalation phase and dose-expansion phase.
Detailed Description

Dose-escalation phase is designed to determine the DLTs (Dose-limiting toxicity) and recommended phase II dose (RP2D) and characterize the safety, tolerability, pharmacokinetics (PK) and Pharmacodynamics (PD) of SY-4798. Other dose regimens may be explored based on the analysis of emerging PK and safety data. At this study phase, SY-4798 will be administered orally once daily (QD) in 28-day treatment cycles to adult patients with advanced solid tumor.

Dose-expansion phase is designed to evaluate the anti-tumor activity (ORR and DOR) of SY-4798 in patients with FGF19+ advanced tumor.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumor
Intervention  ICMJE Drug: SY-4798
FGFR4 selective inhibitor
Other Name: SY-4798 Tablet
Study Arms  ICMJE Experimental: Dose-escalation and Dose-expansion
SY-4798 will be given orally in ascending doses (escalation cohort) until the DLT or RP2D is reached. In dose-expansion phase, preliminary anti-tumor activity will be assessed in FGF19+ advanced tumor.
Intervention: Drug: SY-4798
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 10, 2022)
80
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 15, 2023
Estimated Primary Completion Date April 15, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female, age ≥ 18 years at the time of screening.
  2. Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1.
  3. Escalation Part: Patients must have histological or cytological confirmed advanced solid tumor, which is refractory or inappropriate at this stage to standard therapies or for which no standard therapy exists. In this part, patients with hepatocellular carcinoma (HCC) and Child-Pugh scores of ≤7 are preferred.
  4. Expansion Part: Patients must have histological or cytological confirmed and FGF19 IHC+ advanced solid tumor (patients with HCC should have Child-Pugh scores of ≤7), which is refractory to or inappropriate at this stage to standard therapies or for which no standard therapy exists.
  5. Estimated Life expectancy ≥ 12 weeks.
  6. Must have at least one assessable lesion in dose-escalation part and one measurable lesion in dose-expansion part per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;
  7. Adequate organ function as defined in the below:

    Hepatic function

    Total serum bilirubin (TBIL) ≤ 1.5 times upper limit of normal (ULN); Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 times ULN if no demonstrable liver metastases, or ≤ 5 times ULN in the presence of liver metastases/ in HCC patients.

    Bone marrow function (no blood transfusion or hematopoietic stimulator treatment within 14 days)

    Absolute neutrophil count (ANC) ≥ 1.5 x 109/L; Platelets (PLT) count ≥ 75×109/L; Hemoglobin (Hb) ≥ 85 g/L

    Renal function

    Creatinine clearance ≥ 45 mL/min.

    Coagulation function

    International standardized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN.

  8. Female patients with reproductive potential must have a negative serum pregnancy test within 7 days prior to starting trial treatment, male and female patients of childbearing potential must be willing to completely abstain or agree to use an appropriate method of contraception during the entire study duration and for at least 3 months after the last dose of study medication.
  9. Willingness and ability to give informed consent and follow protocol procedures, and comply with follow-up visit requirements.

Exclusion Criteria:

Patients with any of the following are excluded:

  1. Patients who received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, and other anti-tumor treatment within 4 weeks before the first administration, except for the following: Nitrosourea or mitomycin C was received within 6 weeks before the first administration; Oral fluoropyrimidines and small molecule targeted drugs within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to the first administration; Chinese proprietary medicines with anti-tumor indications were received within 2 weeks before the first administration.
  2. Received other unmarketed investigational drugs or treatments within 4 weeks prior to the first administration.
  3. Have undergone major organ surgery (excluding needle biopsy) or had significant trauma within 4 weeks prior to the first administration.
  4. Have received the treatment of FGFR4 selective or pan-FGFR inhibitors.
  5. Adverse effects of previous antitumor therapy have not recovered to CTCAE 5.0 grade ≤1 (except toxicities that the investigator judged to be of no safety risk, such as alopecia, grade 2 peripheral neurotoxicity, and stable hypothyroidism with hormone replacement therapy).
  6. Patients with central nervous system metastasis or meningeal metastasis with clinical symptoms, or other evidence indicates that the patient's central nervous system metastasis or meningeal metastasis has not been controlled, and those who are judged by the investigators to be unsuitable for inclusion.
  7. Patients with active infection who need systematic anti-infective therapy.
  8. History of immunodeficiency, including positive HIV antibody test.
  9. Active hepatitis B (HBV-DNA > 103 copies/mL or 200 IU/ mL; HBV-DNA> 104 copies/mL or 2000 IU/ mL for patients with HCC), antiviral therapies except interferon are allowed. Hepatitis C virus infection (HCV-RNA >ULN).
  10. A history of serious cardiovascular and cerebrovascular disease, including but not limited to: Severe cardiac rhythm and conduction abnormalities, such as ventricular arrhythmias and degree II-III atrioventricular block requiring clinical intervention; Longer QT interval at rest (QTc > 480 msec) obtained from 3 electrocardiograms (ECGs); Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months prior to first administration; Heart failure with the New York Heart Association (NYHA) Heart function rating ≥ II or left ventricular ejection fraction (LVEF) < 50%; Clinically uncontrolled hypertension.
  11. Uncontrolled effusion in the third space, not suitable for entry as determined by the investigator.
  12. Patient used CYP3A4 potent inhibitors or potent inducers within 7 days before enrollment.
  13. Unable to swallow or conditions that seriously affects gastrointestinal absorption as judged by the investigator.
  14. Known alcohol or drug dependence.
  15. Patients with mental disorders or poor compliance.
  16. Pregnant and/or lactating individuals.
  17. The investigator considered that the subjects had a history of other serious systemic diseases or other reasons that made them unsuitable for the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Yinghui Sun, PhD 86-10-88858616 yhsun@centaurusbio.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05498519
Other Study ID Numbers  ICMJE SY-4798-I-01
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Shouyao Holdings (Beijing) Co. LTD
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Shouyao Holdings (Beijing) Co. LTD
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Yinghui Sun, PhD Shouyao Holdings (Beijing) Co. LTD
PRS Account Shouyao Holdings (Beijing) Co. LTD
Verification Date August 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP