HS-10370 is an oral, highly selective, small molecular inhibitor of KRAS G12C. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10370 in Chinese advanced solid tumor patients.
This is a phase 1/2, first-in-human, open-label, multicenter study of HS-10370, this study has two parts: phase 1 and phase 2. The phase 1 portion consists of dose escalation and dose expansion, which is aimed to assess the safety and tolerability of HS-10370 in subjects with advanced solid tumors and evaluate the preliminary efficacy of HS-10370. Phase 2 will be conducted to evaluate the efficacy of HS-10370 in subjects with locally advanced or metastatic NSCLC with a KRAS G12C mutation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
176
HS-10370 will be administered orally once daily in a continuous regimen
Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGPhase Ia:To determine the maximum tolerated dose (MTD)
Number of participants with dose limiting toxicity
Time frame: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days).
2. Phase Ib/II: To evaluate clinical activity/efficacy of HS-10370 by assessment of objective response rate
Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Time frame: up to 24 months
Incidence and severity of treatment-emergent adverse events
Number of participants with treatment related adverse events.
Time frame: From baseline until 28 days after the last dose
Observed maximum plasma concentration (Cmax) after single dose of HS-10370
In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6
Time frame: From pre-dose to 120 hours after single dose on Day 1
Time to reach maximum plasma concentration (Tmax) after single dose of HS-10370
In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10370 on Day 1 to Day 6.
Time frame: From pre-dose to 120 hours after single dose on Day 1
Apparent terminal half-life (T1/2) after single dose of HS-10370
Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz.
Time frame: From pre-dose to 120 hours after single dose on Day 1
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Duration of response (DOR)
DOR assessed by RECIST 1.1 criteria
Time frame: 24 months
Disease Control Rate (DCR)
DCR assessed by RECIST 1.1 criteria
Time frame: 24 months
Progression-free survival (PFS)
PFS assessed by RECIST 1.1 criteria
Time frame: 24 months
Overall survival (OS)
Time frame: 24 months