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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GFH925 | Experimental | Phase Ia Dose Escalation Subjects with advanced NSCLC and gastrointestinal tumors will be enrolled in dose escalation cohorts based on Bayesian optimal interval (BOIN) design. Phase Ia Dose Expansion Upon completing the dose exploration part of the study and depending on data obtained, dose expansion may proceed with responsive groups consisting of subjects with KRAS G12C mutant advanced NSCLC. Dose expansion may be done concurrently. Phase Ib Subjects with KRAS G12C mutant advanced colorectal cancer or other tumors will be enrolled and treated at the monotherapy RP2D to evaluate the efficacy. Phase 2 Subjects with KRAS G12C mutant advanced NSCLC will be enrolled and treated at the monotherapy RP2D to evaluate the safety and efficacy. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GFH925 | Drug | Administered as an oral tablet formulation |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Baseline to 24 Months |
| Phase Ia: Incidence of dose-limiting toxicity (DLT) events | Safety measures | At the end of Cycle 1(each cycle is 21 days) |
| Phase Ib: ORR per RECIST 1.1 | Efficacy measures | Continuous evaluation during treatment |
| Phase II: ORR assessed by Independent Radiographic Review Committee (IRRC) according to RECIST 1.1 | Efficacy measures | Continuous evaluation during treatment |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Guangdong Provincial People's Hospital | Guangzhou | Guangdong | 510000 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39127176 | Derived | Zhou Q, Meng X, Sun L, Huang D, Yang N, Yu Y, Zhao M, Zhuang W, Guo R, Hu Y, Pan Y, Shan J, Sun M, Yuan Y, Fan Y, Huang J, Liu L, Chu Q, Wang X, Xu C, Lin J, Huang J, Huang M, Sun J, Zhang S, Zhou H, Wu YL. Efficacy and Safety of KRASG12C Inhibitor IBI351 Monotherapy in Patients With Advanced NSCLC: Results From a Phase 2 Pivotal Study. J Thorac Oncol. 2024 Dec;19(12):1630-1639. doi: 10.1016/j.jtho.2024.08.005. Epub 2024 Aug 9. |
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Efficacy measures |
| 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 | 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 | Baseline to 24 Months |
| Phase Ib and Phase II: Plasma concentration (including Ctrough) after multiple dose administration in subjects | Efficacy measures and safety measures | To complete 3 treatments cycles(each cycle is 21 days) |