A Phase I Study of SY-4835 in Patients With Advanced Solid Tumors

NCT05291182 | Unknown Phase 1

• 1 other identifier: SY-4835-1
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1, open-label, single-arm, first-in-human study to evaluate the safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of SY-4835 administered orally in patients with advanced solid tumors.

Conditions

Advanced Solid Tumor

Keywords

SY-4835; WEE1; Advanced solid tumor

Outcome Measures

Primary Outcomes (3)

• Adverse events (AE), serious adverse events (SAEs), suspected unexpected serious adverse reaction (SUSAR), physical examination, etc. (CTCAE 5.0 standard)

  Characterization of the safety and tolerability

  Up to 24 months

• Tolerability: Ratio of Dose reductions or interruptions

  Characterization of the safety and tolerability

  Up to 24 months

• Incidence rate of dose limiting toxicities (DLTs)

  Maximum Tolerated Dose(s) (MTD(s)) and recommended phase 2 dose (RP2D(s))

  cycle 1 (each cycle is 21 days)

Secondary Outcomes (8)

• Pharmacokinetics (Cmax) for SY-4835

  Cycle 1 (each cycle is 21 days)

• Pharmacokinetics (Tmax) for SY-4835

  Cycle 1 (each cycle is 21 days)

• Pharmacokinetics (AUC0-t) for SY-4835

  Cycle 1 (each cycle is 21 days)

• Pharmacokinetics (t½) for SY-4835

  Cycle 1 (each cycle is 21 days)

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

  Up to 24 months

Study Arms (1)

Dose-escalation

EXPERIMENTAL

The study is conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of SY-4835.

Drug: SY-4835

Interventions

SY-4835 DRUG

WEE1 inhibitor

Also known as: SY-4835 tablets

Dose-escalation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must understand andvoluntarily sign the informed consent form, willing to follow and able to complete all study procedures.
• Male or female (age of 18\~75 years old ).
• Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1.
• Estimated life expectancy ≥3 months.
• Histological or cytological confirmation of a advanced solid tumor, that failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist.
• At least 1 measureable lesion for solid tumors assessed using RECIST 1.1.
• Patients must have adequate organ function as defined below (no supportive treatment for the following parameters within 7 days prior to testing):
• Liver function:
• Patients without hepatic metastasis, aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3 times institutional upper limit of normal (ULN), total bilirubin (TBIL) ≤ 1.5 times ULN; Patients with hepatic metastasis, AST, ALT ≤ 5 times ULN, TBIL ≤ 1.5 times ULN; Patients with hepatoma carcinoma, AST and ALT ≤ 5 times ULN, TBIL ≤ 2.5 times ULN.
• Bone marrow function:
• Absolute neutrophil count (ANC) ≥ 1.5×10\^9/L; Platelets (PLT) count ≥ 75×10\^9/L; Hemoglobin (HB) ≥ 80 g/L.
• Renal function:
• Creatinine clearance ≥ 45 mL/min or serum creatinine ≤ 1.5 times ULN.
• Coagulation function:
• Activated partial thromboplastin time (APTT) ≤ 1.5×ULN; International Normalized ratio (INR) ≤ 1.5×ULN.

You may not qualify if:

• Have received chemotherapy, radiotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor therapy within 3 weeks prior to the first use of the study drug, except for the following:
• Nitrosourea or mitomycin C were used within 6 weeks prior to the first use of the study drug; Oral fluorouracil and small molecule targeted drugs were used within 2 weeks or within 5 half-lives prior to the first use of the study; Chinese medicines were used within 2 weeks prior to the first use of the study drug.
• Have received an unmarketed clinical investigational drug or treatment within 4 weeks prior to the first use of the study drug.
• Had major organ surgery (excluding needle biopsy) or had significant traumatism within 4 weeks prior to the first use of study drug.
• History of any WEE1 inhibitor treatment.
• With the exception of alopecia and ≤ Grade 2 peripheral neuropathy, any unresolved toxicities from prior treatment ≤ Grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE) at the time of starting study treatment.
• Evidence of central nervous system (CNS) metastases accompanied with clinical symptoms, or other evidence of uncontrolled CNS metastases judged by investigators that the patient should not participate in the study.
• Patients have serous effusion (such as pleural effusion, peritoneal effusion, pericardial effusion, etc.) with clinical symptoms, effusions will still increase after 2 weeks of conservative treatment (excluding drainage).
• Patients with active uncontrolled systemic bacterial, viral, or fungal infection despite optimal treatment.
• Active hepatitis B (HBsAg-positive and HBV-DNA ≥ 2000 IU/ mL), Hepatitis C virus infection (HCVAb-positive and HCV-RNA ≥ 1000 IU/ml); Human immunodeficiency virus antibody (HIV Ab) positive; Active syphilis.
• Have serious cardiovascular and cerebrovascular diseases, including but not limited to:
• Severe arrhythmias or abnormal cardiac conduction, such as ventricular arrhythmias requiring clinical intervention, degree ii-iii atrioventricular block, etc; Mean resting corrected QT interval (QTcF) \> 470 msec obtained from 3 electrocardiograms (ECGs); Had acute coronary syndrome, congestive heart failure, aortic dissection, or other grade 3 or higher cardio-cerebrovascular events within 6 months prior to the first use of study drug; Heart failure (New York Heart Association, NYHA) class ≥ II or left ventricular ejection fraction (LVEF) \< 40 %; Hypertension remains uncontrolled after aggressive antihypertensive therapy. Uncontrolled hypertension was defined as systolic blood pressure \> 185 mmHg and/or diastolic blood pressure \> 110 mmHg measured on 3 repetitions at least 10 minutes apart.
• Prescription or non-prescription drugs known as moderate to strong inhibitors / inducers of CYP3A4 and CYP2D6 within 7 days prior to the first dose of study treatment.
• Patients with alcohol and/or drug dependence.
• Women who are breastfeeding.

Sponsors & Collaborators

• Shouyao Holdings (Beijing) Co. LTD: lead

Study Sites (1)

Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200127, 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: March 2, 2022
• First Posted: March 22, 2022
• Study Start: June 28, 2021
• Primary Completion: June 28, 2024
• Study Completion: December 28, 2024
• Last Updated: February 2, 2024

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)