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

NCT05498519 | Unknown Phase 1

• 1 other identifier: SY-4798-I-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor

Keywords

SY-4798; FGFR4; Advanced solid tumor; FGF19+ advanced tumor

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities (DLTs)

  Maximum Tolerated Dose(s) (MTD(s)) and/or recommended phase 2 dose (RP2D(s)) in Cycle 1.

  Escalation Cycle 1 (28 days)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Characterization of the safety and tolerability as determined by changes in laboratory values and electrocardiograms.

  Up to 24 months

Secondary Outcomes (7)

• Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria

  Up to 24 months

• Duration of response (DOR)

  Up to 24 months

• Pharmacokinetics (Cmax) for SY-4798

  Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days)

• Pharmacokinetics (Tmax) for SY-4798

  Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days)

• Pharmacokinetics (AUC0-t) for SY-4798

  Protocol-defined time points during Cycles 1 and 2 of treatment (each cycle is 28 days)

Study Arms (1)

Dose-escalation and Dose-expansion

EXPERIMENTAL

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.

Drug: SY-4798

Interventions

SY-4798 DRUG

FGFR4 selective inhibitor

Also known as: SY-4798 Tablet

Dose-escalation and Dose-expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age ≥ 18 years at the time of screening.
• Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1.
• 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.
• 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.
• Estimated Life expectancy ≥ 12 weeks.
• 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;
• 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.

You may not qualify if:

• Patients with any of the following are excluded:
• 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.
• Received other unmarketed investigational drugs or treatments within 4 weeks prior to the first administration.
• Have undergone major organ surgery (excluding needle biopsy) or had significant trauma within 4 weeks prior to the first administration.
• Have received the treatment of FGFR4 selective or pan-FGFR inhibitors.
• 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).
• Patients with active infection who need systematic anti-infective therapy.
• History of immunodeficiency, including positive HIV antibody test.
• 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).
• 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.
• Uncontrolled effusion in the third space, not suitable for entry as determined by the investigator.
• Patient used CYP3A4 potent inhibitors or potent inducers within 7 days before enrollment.
• Unable to swallow or conditions that seriously affects gastrointestinal absorption as judged by the investigator.
• Known alcohol or drug dependence.
• Patients with mental disorders or poor compliance.

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (1)

Shanghai East Hospital

Shanghai, 200123, China

RECRUITING

Study Officials

• Yinghui Sun, PhD

  Shouyao Holdings (Beijing) Co. LTD

  STUDY DIRECTOR

Central Study Contacts

Yinghui Sun, PhD

CONTACT

86-10-88858616; yhsun@centaurusbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 12, 2022
• Study Start: April 15, 2021
• Primary Completion: April 15, 2024
• Study Completion: April 15, 2024
• Last Updated: May 11, 2023

Record last verified: 2023-05

Locations

CN (1)