Lapatinib Plus Trametinib in KRAS Mutant NSCLC

Study Overview
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Brief Summary
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This is an open-label phase I/II multi-center study consisting of two parts. Part A of this study is designed to identify the recommended phase 2 dose (RP2D) of lapatinib combined with trametinib in patients with metastatic KRASm and PIK3CA wild-type (PIK3CAwt) non-small cell lung cancer (NSCLC). Part B is designed to perform a randomized comparison of the lapatinib-trametinib combination versus standard of care therapy in patients with metastatic KRASm/PIK3CAwt NSCLC.

Official Title
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Phase I/II Study With Lapatinib Plus Trametinib in Patients With Metastatic KRAS Mutant Non-small Cell Lung Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Lapatinib
* Drug: trametinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological or cytological proof of metastatic NSCLC; for PART B: treated with first line therapy for metastatic disease only. Written documentation of a known pathogenic KRAS (exon 2, 3 or 4) mutation and PIK3CA wild-type (exon 9 and 20) Age ≥ 18 years Able and willing to give written informed consent WHO performance status of 0 or 1 (part A and B) Exclusion Criteria: Any treatment with investigational drugs within 30 days prior to receiving the first dose of investigational treatment. History of another primary malignancy Symptomatic or untreated leptomeningeal disease Symptomatic brain metastasis History of interstitial lung disease or pneumonitis Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients Retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), or a history of uveitis, retinal vein occlusion, central serous retinopathy, or retinal detachment Patients with left ventricular ejection fraction (LVEF) < 50%

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: lapatinib + trametinib<br>lapatinib: oral tablets, once daily trametinib: oral tablets, once daily | Drug: Lapatinib<br> <br> Drug: trametinib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of dose-limiting toxicities |  | 1.5 years | 
| progression free survival |  | 2.5 years | 
| overall response rate |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adveres events |  | 2.5 years | 
| Plasma concentration |  | 2.5 years | 
| Duration of response |  | 2.5 years | 
| Time to response |  | 2.5 years | 
| Overall survival |  | 3 years |