Phase Ia: To evaluate the safety/tolerability of GFH925 in subjects with KRAS G12C-mutated advanced solid tumors; To estimate the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of GFH925. Phase Ib: To evaluate the efficacy of GFH925 in subjects with KRAS G12C mutant advanced colorectal cancer or other tumors. Phase II: To evaluate the efficacy of GFH925 in subjects with KRAS G12C mutant advanced non-small cell lung cancer (NSCLC).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
334
Administered as an oral tablet formulation
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Phase Ia: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs); changes in laboratory tests, vital signs, physical examinations, electrocardiograms (ECGs)
Safety measures
Time frame: Baseline to 24 Months
Phase Ia: Incidence of dose-limiting toxicity (DLT) events
Safety measures
Time frame: At the end of Cycle 1(each cycle is 21 days)
Phase Ib: ORR per RECIST 1.1
Efficacy measures
Time frame: Continuous evaluation during treatment
Phase II: ORR assessed by Independent Radiographic Review Committee (IRRC) according to RECIST 1.1
Efficacy measures
Time frame: Continuous evaluation during treatment
Phase Ia: PK parameters of GFH925 include but are not limited to: Cmax, Tmax, AUC, t1/2, CL/F and Vd/F
Efficacy measures and safety measures
Time frame: To complete 3 treatments cycles(each cycle is 21 days)
Phase Ia: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, disease control rate (DCR), duration of response (DoR), time to response (TTR), progression-free survival (PFS),Overall survival (OS)
Efficacy measures
Time frame: Continuous evaluation during treatment
Phase Ib and Phase II: DCR, DoR, TTR, PFS per RECIST 1.1, progression-free survival rate at 6 and 12 months, overall survival rate at 12 months
Efficacy measures
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Time frame: Continuous evaluation during treatment
Phase Ib and Phase II: Incidence and severity of AEs, SAEs, AEs leading to treatment interruption, and AEs leading to treatment discontinuation of GFH925 monotherapy
Safety measures
Time frame: Baseline to 24 Months
Phase Ib and Phase II: Plasma concentration (including Ctrough) after multiple dose administration in subjects
Efficacy measures and safety measures
Time frame: To complete 3 treatments cycles(each cycle is 21 days)