A Study of GFH925 in Combination With Cetuximab in Previously Untreated Advanced NSCLC Harboring KRAS G12C Mutation

Study Overview
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Brief Summary
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This is a Phase Ib/II study. The objectives are to evaluate the safety/tolerability and efficacy of GFH925 in combination with Cetuximab in advanced KRAS G12C mutant NSCLC, to characterize pharmacokinetics (PK) of GFH925 in combination with Cetuximab in advanced KRAS G12C mutant NSCLC

Official Title
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A Phase Ib/II, Multi-Center, Open-Label Study to Evaluate the Safety/Tolerability, Pharmacokinetics, and Efficacy of GFH925 in Combination With Cetuximab in Previously Untreated Advanced NSCLC Harboring KRAS G12C Mutation

Conditions
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Advance Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: GFH925
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has provided informed consent form (ICF). Males or females aged ≥ 18 years. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 1. Life expectancy > 3 months judged by the investigator. Have histologically or cytologically confirmed advanced KRAS G12C-mutated NSCLC. Have at least one measurable lesion per RECIST 1.1. Have sufficient organ functions. With toxicities left from prior anti-tumor therapy resolved to baseline or CTCAE Grade 1 (neurotoxicity or alopecia ≤ Grade 2). Women of childbearing potential (WOCBP) and male patients with WOCBP partners must agree to use effective contraception method during the study specified period. Exclusion Criteria: With clinically significant cardiovascular diseases. With active central nervous system (CNS) metastases and/or carcinomatous meningitis. With clinically significant gastrointestinal diseases. With active infections. With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion. With uncontrolled systemic diseases, such as hypertension or diabetes. Prior treatment with an inhibitor specific to KRAS G12C. Major surgery within 4 weeks prior to initiation of study treatment. With known allergies to the study drugs or components. Pregnant or lactating females, or female patients intend to become pregnant during participation.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GFH925+Cetuximab<br> | Drug: GFH925<br>* GFH925 tablets administered orally daily.<br>Drug: Cetuximab<br>* Cetuximab administered intravenously Q2W.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ib: adverse events | defined as number of patients with treatment emergent AEs | 28 days | 
| Phase II: objective response rate | defined as the percent of patients documented a PR/CR | up to 1 year after last patient in |