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

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

• TQ-B3101 (Drug): 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 .

Primary outcomes

• The maximum tolerated dose (MTD) of TQ-B3101 [48 weeks]: The highest dose at which no more than 33% of the subjects experience a dose-limiting toxicity (DLT) during treatment
• The type of dose-limiting toxicity(ies) (DLT[s]) of TQ-B3101 [For 4 weeks for DLTs]: 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
• Pharmacokinetics of TQ-B3101 (in whole blood):Peak Plasma Concentration(Cmax) [up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL)]: 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）
• Pharmacokinetics of TQ-B3101 (in whole blood):Peak time（Tmax） [up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL)]: 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）
• Pharmacokinetics of TQ-B3101 (in whole blood):Half life（t1/2） [up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL)]: 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）
• Pharmacokinetics of TQ-B3101 (in whole blood):Area under the plasma concentration versus time curve (AUC) [up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL)]: 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）
• Pharmacokinetics of TQ-B3101 (in whole blood):Clearance（CL） [up to 28 Days (endpoint when the two consecutive time points of blood drug concentration <150 DPM/mL)]: 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）

Secondary outcomes

• Objective Response Rate(ORR) [each 28 days up to intolerance the toxicity or PD (up to 24 months)]: 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).

Sex: All, ages: 18 Years to 70 Years

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

• Results publication: Lu S, Pan H, Wu L, Yao Y, He J, Wang Y, Wang X, Fang Y, Zhou Z, Wang X, Cai X, Yu Y, Ma Z, Min X, Yang Z, Cao L, Yang H, Shu Y, Zhuang W, Cang S, Fang J, Li K, Yu Z, Cui J, Zhang Y, Li M, Wen X, Zhang J, Li W, Shi J, Xu X, Zhong D, Wang T, Zhu J. Efficacy, safety and pharmacokinetics of Unecritinib (TQ-B3101) for patients with ROS1 positive advanced non-small cell lung cancer: a Phase I/II Trial. Signal Transduct Target Ther. 2023 Jun 30;8(1):249. doi: 10.1038/s41392-023-01454-z. PMID 37385995