TR64 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a open-label, dose escalation, accelerated titration combined 3+3 design, phase I study, to evaluate the safety and tolerability, and to determine the RP2D of TR64 when administered qd in patients with advanced solid tumors. Up to 6 cohorts of 1-6 or 3-6 patients each will be treated in the study.

Detailed Description
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Patients will receive study treatment until criteria for study termination are met. A Safety Follow-up Visit will be conducted 28 days (±7 days) after the last dose of study treatment. Patients who discontinue study treatment for reasons other disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient withdraws consent, is lost to follow-up, death, or until the Sponsor stops the study, whichever comes first. Adverse events will be assessed using the NCI Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. Tumor response will be assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI) scan using RECIST 1.1 criteria, assessed by the investigator.

Official Title
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A Single-arm, Open-Label, Dose Escalation , Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TR64 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: TR64


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fully understand the procedures of the clinical study and participate voluntarily with signed and dated written informed consent form, comply with the requirements of the study protocol. Males and/or females at least 18 years old when signing the informed consent form. Histologically or cytologically confirmed patients with advanced malignant solid tumors, eligible patients must have failed standard treatment, no standard treatment, or not suitable for standard treatment at this stage as determined by the investigator. Measurable disease with at least one lesion amenable to response assessment per RECIST 1.1. Eastern cooperative oncology group performance status (ECOG) ≤2 at screening. Life expectancy of at least 3 months. Acceptable organ function: Absolute neutrophil count(ANC)≥1.5×109/L; Platelet count(PLT)≥90×109/L; Hemoglobin(Hb)≥90 g/L; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN); Alanine aminotransferase(ALT)≤2.5×ULN; Aspartate aminotransferase(AST)≤2.5×ULN; Creatinine clearance ≥50ml/min. Fertile male and female must agree to use medically approved contraceptives during the study and within 90 days after the last dose of the study. Exclusion Criteria: Known or suspected allergies to any of the investigational drug composition. Medical history and surgical history excluded according to the protocol. Any previous medical treatment history exclude from the protocol. Abnormal laboratory results exclude from the protocol. pregnant and lactating women (currently breast-feeding or less than six months after delivery although not breast-feeding). Subjects may not be able to complete the study duo to poor compliance or other reasons, or unsuitable for the study by the investigator's judgment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TR64<br>Daily doses by oral administration on each day of each 28 day cycle. Starting dose is 25mg, with escalation to 400mg, and subsequent dose escalation using a modified Fibonacci algorithm. | Drug: TR64<br>* TR64 tablets will be given daily for 28 days in 28-day cycles until there appears evidence of progressive disease, intolerable toxicity, or the subject discontinues from the study treatment for other reasons.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events and Serious Adverse Events | Frequency, duration and severity of Adverse Events and Serious Adverse Events evaluated by NCI CTCAE v5.0 | From the first dose to within 28 days after the last dose | 
| Dose limited toxicities | Incidence of dose limited toxicities | within 28 days after the first dose | 
| Maximum tolerated dose | Evaluated by safety review committee | Throughout the study for approximately 2 years | 
| Recommended phaseII dose | Evaluated by safety review committee | Throughout the study for approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUClast | Characterize the pharmacokinetic profile of TR64 | within 35 days after the first dose | 
| AUCinf | Characterize the pharmacokinetic profile of TR64 | within 35 days after the first dose | 
| Cmax | Characterize the pharmacokinetic profile of TR64 | within 35 days after the first dose | 
| Tmax | Characterize the pharmacokinetic profile of TR64 | within 35 days after the first dose | 
| CL/F | Characterize the pharmacokinetic profile of TR64 | within 35 days after the first dose | 
| Vz/F | Characterize the pharmacokinetic profile of TR64 | within 35 days after the first dose | 
| Terminal half-life (T1/2) | Characterize the pharmacokinetic profile of TR64 | within 35 days after the first dose |