Advanced Solid Tumor
Conditions
Keywords
SY-4835, WEE1, Advanced solid tumor
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.
Detailed description
This study is a first-in-human phase I study of SY-4835, a potent WEE1 inhibitor, in patients with advanced solid tumor. Dose-escalation study is conducted to evaluate primary endpoints and secondary endpoints including the maximum tolerated dose (MTD), Dose-limiting toxicity (DLT), pharmacokinetics (PK) parameters and recommended phase II dose (RP2D), and the safety, tolerability and pharmacokinetics (PK) profiles of SY-4835 are characterized in this study.
Interventions
DRUGSY-4835
WEE1 inhibitor
Sponsors
Shouyao Holdings (Beijing) Co. LTD
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* For inclusion in this study, patients must fulfil the following criteria: 1. Must understand andvoluntarily sign the informed consent form, willing to follow and able to complete all study procedures. 2. Male or female (age of 18\ 75 years old ). 3. Eastern Collaboration Oncology Group (ECOG) performance status (PS) scored of 0-1. 4. Estimated life expectancy ≥3 months. 5. 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. 6. At least 1 measureable lesion for solid tumors assessed using RECIST 1.1. 7. 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. 8. Women of childbearing age performed a serum pregnancy test within 7 days before the initiation of treatment, and agreed to adopt a reliable and effective contraceptive method during the trial and within 90 days after the final administration of the study drug.
Exclusion criteria
* Patients must not enrol in this study if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AE), serious adverse events (SAEs), suspected unexpected serious adverse reaction (SUSAR), physical examination, etc. (CTCAE 5.0 standard) | Up to 24 months | Characterization of the safety and tolerability |
| Tolerability: Ratio of Dose reductions or interruptions | Up to 24 months | Characterization of the safety and tolerability |
| Incidence rate of dose limiting toxicities (DLTs) | cycle 1 (each cycle is 21 days) | Maximum Tolerated Dose(s) (MTD(s)) and recommended phase 2 dose (RP2D(s)) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (Cmax) for SY-4835 | Cycle 1 (each cycle is 21 days) | Defined as maximum observed plasma concentration |
| Pharmacokinetics (Tmax) for SY-4835 | Cycle 1 (each cycle is 21 days) | Defined as time to maximum plasma concentration |
| Pharmacokinetics (AUC0-t) for SY-4835 | Cycle 1 (each cycle is 21 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-4835 | Cycle 1 (each cycle is 21 days) | Defined as the apparent plasma terminal phase disposition half-life |
| Overall Response Rate (ORR) as assessed by RECIST 1.1 criteria | Up to 24 months | Preliminary measure of anti-tumor activity of SY-4835 |
| Progression Free Survival (PFS) | Up to 24 months | Preliminary measure of anti-tumor activity of SY-4835 |
| Disease control rate (DCR) | Up to 24 months | Preliminary measure of anti-tumor activity of SY-4835 |
| Duration of response (DOR) | Up to 24 months | Preliminary measure of anti-tumor activity of SY-4835 |
Countries
China
Contacts
Primary ContactYinghui Sun, PhD
Outcome results
None listed