TR128 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a open-label, 3+3 design, dose escalation and expansion, phase I study, to evaluate the safety and tolerability, and to determine the Recommended Phase II Dose (RP2D) of TR128 when administered qd in patients with advanced solid tumors. Up to 5 cohorts of 3-6 patients each will be treated in dose escalation phase of the study. One cycle is 28 days. Dose expansion phase to further evaluate the safety, tolerability and preliminary anti-tumor activity of TR128 at the RP2D.

Detailed Description
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This phase I study of TR128 will investigate the tolerability, safety, pharmacokinetics (PK) and preliminary efficacy of TR128, and will define the maximum tolerated dose (MTD) of TR128 using 3+3 design. A dose expansion phase will identify the recommended phase 2 dose. In this clinical study, TR128 is given orally daily. A treatment cycle is defined as 28 days. Patients will receive study treatment until criteria for study termination are met. A safety follow-up visit will be conducted 28 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 (AEs) 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 RECIST1.1 criteria, assessed by the investigator.

Official Title
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A Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetics of TR128 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: TR128


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) ≤1 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; International Normalized Ratio (INR) or Prothrombin Time (PT)≤1.5×Upper limit of normal value (ULN), Activated Partial Thromboplastin Time (APTT)≤1.5×ULN ; Total bilirubin(TBIL)≤1.5×Upper limit of normal value(ULN) (≤3× ULN if there is liver involvement); Alanine aminotransferase(ALT)≤2.5×ULN and aspartate aminotransferase(AST)≤2.5×ULN (≤ 5 × ULN if there is liver involvement); Creatinine (Cr) ≤1.5×ULN or Creatinine Clearance (CCr) ≥50 ml/min (calculated by Cockcroft-Gault formula). fertile male and female must agree to use medically approved contraceptives during the study and within 6 months after the last dose of the study. Exclusion Criteria: 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). unsuitable for the study by the investigator's judgment.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Dose escalation and expansion
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TR128<br> | Drug: TR128<br>* TR128 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. Starting dose is 100mg, with escalation to 500mg.<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 30 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 phase II 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 TR128 | within 31 days after the first dose | 
| AUCinf | Characterize the pharmacokinetic profile of TR128 | within 31 days after the first dose | 
| Cmax | Characterize the pharmacokinetic profile of TR128 | within 31 days after the first dose | 
| Tmax | Characterize the pharmacokinetic profile of TR128 | within 31 days after the first dose | 
| CL/F | Characterize the pharmacokinetic profile of TR128 | within 31 days after the first dose | 
| Vz/F | characterize the pharmacokinetic profile of TR128 | within 31 days after the first dose | 
| Terminal half-life (T1/2) | Characterize the pharmacokinetic profile of TR128 | within 31 days after the first dose | 
| ORR | Efficacy-overall response rate | throughout the study for approximately 2 years | 
| PFS | Efficacy-progression free survival | throughout the study for approximately 2 years | 
| DOR | Efficacy-duration of response | throughout the study for approximately 2 years | 
| DCR | Efficacy-disease control rate | throughout the study for approximately 2 years |