A Study of IBI351 in Combination With Cetuximab in Subjects With KRAS G12C Mutated Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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Phase 1b consists of combined dose escalation phase and dose expansion phase. Phase 3 study will compare efficacy and safety of IBI351 combined with cetuximab versus chemotherapy in treatment of KRAS G12C-mutated metastatic colorectal cancer

Detailed Description
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A Phase 1b study of the safety, tolerability and preliminary efficacy of IBI351 combined with cetuximab in the treatment of KRAS G12C mutant metastatic colorectal cancer will be conducted based on recommended dose of IBI351, which consists of combined dose escalation phase and dose expansion phase. After confirming the efficacy and safety of IBI351 combined with cetuximab in Phase Ib, an open-label Phase 3 study of the efficacy and safety of IBI351 combined with cetuximab versus oxaliplatin-based mFOLFOX6 regimen or irinotecan-based FOLFIRI with or without bevacizumab in treatment of KRAS G12C-mutated metastatic colorectal cancer will be conducted.

Official Title
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An Open-label, Multicenter, Phase Ib/III Study of Efficacy and Safety of IBI351 in Combination With Cetuximab in Subjects With KRAS G12C Mutated Metastatic Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: IBI351
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female subjects, ≥ 18 years and ≤ 75 years have documentation of KRAS G12C mutation at least one measurable lesion per RECISTv1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. life expectancy of >12 weeks, in the opinion of the investigator Exclusion Criteria: history of deep venous thrombosis or any other serious thromboembolism within 3 months prior to enrollment.. history of radiation-induced pneumonitis, idiopathic pneumonia, active pneumonia, pulmonary fibrosis, diffuse pulmonary interstitial disease, or organizing pneumonia. surgical procedures (excluding needle biopsy) performed within 28 days prior to enrollment that may affect the dosing or study assessments in this study. received therapeutic or palliative radiation therapy within 14 days prior to enrollment pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI351+Cetuximab<br>IBI351 recommended dose+Cetuximab 500mg/m2 IV Q2W | Drug: IBI351<br>* IBI351 is administered orally<br>* Other names: GFH925;Drug: Cetuximab<br>* Cetuximab is administered intravenously<br>* Other names: Erbitux;|
| Experimental: IBI351<br>IBI351 recommended dose | Drug: IBI351<br>* IBI351 is administered orally<br>* Other names: GFH925;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of DLTs (Dose-limiting Toxicity) in the Combined Dose Escalation Phase |  | 28 days during the first 4-week cycle | 
| Objective response rate (ORR) |  | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of serious treatment-emergent AEs (TEAEs) , treatment-related adverse event(TRAE), adverse events (SAEs) |  | up to 30 days after the last administration | 
| Number of participants with abnormality in vital signs |  | up to 30 days after the last administration | 
| Number of participants with abnormality in hematology parameters |  | up to 30 days after the last administration | 
| Number of participants with abnormality in clinical chemistry parameters |  | up to 30 days after the last administration | 
| Number of participants with abnormality in routine urinalysis parameters |  | up to 30 days after the last administration | 
| Number of participants with abnormality in ECG parameters |  | up to 30 days after the last administration |