A Phase I Study of TQ-B3101 on Tolerance and Pharmacokinetics

Study Overview
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Brief Summary
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To study the pharmacokinetic characteristics of TQ-B3101 in the human body, recommend a reasonable regimen for subsequent research.

Detailed Description
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single arm, single or repeat dosing of TQ-B3101 on patients with solid tumors.

Official Title
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Phase I Study of Tolerance and Pharmacokinetics of TQ-B3101 in Patients With Advanced Cancer

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: TQ-B3101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological documentation of Advanced solid tumors Lack of the standard treatment or treatment failure 18-70years,ECOG PS:0-1,Life expectancy of more than 3 months Main organs function is normal Women of childbearing potential should agree to use and utilize an adequate method of contraception (such as intrauterine device，contraceptive and condom) throughout treatment and for at least 6 months after study is stopped；the result of serum or urine pregnancy test should be negative within 7 days prior to study enrollment，and the patients required to be non-lactating；Man participants should agree to use and utilize an adequate method of contraception throughout treatment and for at least 6 months after study is stopped Patients should participate in the study voluntarily and sign informed consent Exclusion Criteria: Patients with treatment failure by ALK/ROS1 inhibitor Patients with anti-teratment,radiotherapy or surgery within 4 weeks Patients participated in other anticancer drug clinical trials within 4 weeks or ALK/ROS1 inhibitor within 1 week Blood pressure unable to be controlled(systolic pressure>140 mmHg，diastolic pressure>90 mmHg). Patients with Grade 1 or higher myocardial ischemia, myocardial infarction or malignant arrhythmias(including QT≥470ms) Patients with non-healing wounds or fractures Patients with drug abuse history and unable to get rid of or Patients with mental disorders History of immunodeficiency Patients with concomitant diseases which could seriously endanger their own safety or could affect completion of the study according to investigators' judgment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: TQ-B3101<br>TQ-B3101 QD po and it should be continued until disease progression or intolerable toxicity or patients withdrawal of consent | Drug: TQ-B3101<br>* Escalating doses of TQ-B3101 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 100 mg to 500 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The maximum tolerated dose (MTD) of TQ-B3101 | The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment | 48 weeks | 
| The type of dose-limiting toxicity(ies) (DLT[s]) of TQ-B3101 | Subjects within 28 days after treatment appear the following toxicity reaction relate to the drug ：III °or above of non-hematological toxicity,IV°hematological toxicity ,Neutropenia associated with fever | For 4 weeks for DLTs | 
| Pharmacokinetics of TQ-B3101 (in whole blood):Peak Plasma Concentration(Cmax) | Peak Plasma Concentration(Cmax),Cmax in ng/mL.In the study of single-dose, full PK profiles will be obtained at H-24/H-12/H0/H0.5/H1/H2/H3/H4/H6/H10/H24/H36/H48/H72/H96/H120/H144（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D1/D8/D15/D21/D28（D means Day） | up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of TQ-B3101 (in whole blood):Peak time（Tmax） | Peak time（Tmax）,Tmax in h.In the study of single-dose, full PK profiles will be obtained at H-24/H-12/H0/H0.5/H1/H2/H3/H4/H6/H10/H24/H36/H48/H72/H96/H120/H144（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D1/D8/D15/D21/D28（D means Day） | up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of TQ-B3101 (in whole blood):Half life（t1/2） | Half life（t1/2）,t1/2 in h.In the study of single-dose, full PK profiles will be obtained at H-24/H-12/H0/H0.5/H1/H2/H3/H4/H6/H10/H24/H36/H48/H72/H96/H120/H144（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D1/D8/D15/D21/D28（D means Day） | up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of TQ-B3101 (in whole blood):Area under the plasma concentration versus time curve (AUC) | Area under the plasma concentration versus time curve (AUC), AUC in ng.h/mL.In the study of single-dose, full PK profiles will be obtained at H-24/H-12/H0/H0.5/H1/H2/H3/H4/H6/H10/H24/H36/H48/H72/H96/H120/H144（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D1/D8/D15/D21/D28（D means Day） | up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 
| Pharmacokinetics of TQ-B3101 (in whole blood):Clearance（CL） | Clearance（CL）,CL in L/h.In the study of single-dose, full PK profiles will be obtained at H-24/H-12/H0/H0.5/H1/H2/H3/H4/H6/H10/H24/H36/H48/H72/H96/H120/H144（H means Hour）.In the study of multiple-dose,full PK profiles will be obtained at D1/D8/D15/D21/D28（D means Day） | up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate(ORR) | Percentage of participants with OR based assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). | each 28 days up to intolerance the toxicity or PD (up to 24 months) |