TSN084 is a novel type II kinase inhibitor with demonstrated anti-tumor effects in vitro and in vivo and targets multiple tyrosine kinases, such as c-MET, FLT3, TRK and serine/threonine kinase CDK8/19. This phase 1a/1b study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of TSN084 in advanced or metastatic malignancies in China.
The phase 1a part will begin with an exploration of TSN084 dose and regimen to determine the maximum tolerated dose (MTD) and/or recommended dose for further investigation (i.e., RP2D). In Phase 1b part, separate cohorts of patients with different histological diagnosis will be evaluated for the clinical activity and efficacy of TSN084 at the recommended dose.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
114
TSN084 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGPeking university cancer hospital
Beijing, Beijing Municipality, China
RECRUITINGDose limiting toxicity (DLT)
Number of patients with dose limiting toxicity, to determine the MTD and/or RP2D
Time frame: 28 days
Incidence of Treatment-Emergent Adverse Events (TEAE)
Incidence of TEAE, Serious Adverse Event (SAE), their relationship with the investigational product and severity. Adverse events will be graded according to NCI-CTCAE V5.0.
Time frame: Up to 3 years
Maximum plasma concentration (Cmax)
To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.
Time frame: 28 days
Time to Cmax (Tmax)
To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.
Time frame: 28 days
Area under the concentration versus time curve from time 0 to the last measurable concentration (AUC 0-t)
To characterize the pharmacokinetic (PK) properties of TSN084 in patients with advanced malignant tumors.
Time frame: 28 days
Objective response rate (ORR)
Tumor response assessments by RECIST v1.1
Time frame: Up to 3 years
Duration of response (DoR)
Tumor response assessments by RECIST v1.1
Time frame: Up to 3 years
Disease control rate (DCR)
Tumor response assessments by RECIST v1.1
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Time frame: Up to 3 years
Time to response (TTR)
Tumor response assessments by RECIST v1.1
Time frame: Up to 3 years
Progression free survival (PFS)
Tumor response assessments by RECIST v1.1
Time frame: Up to 3 years
Overall survival (OS)
Time frame: Up to 3 years