A Study of Gemcitabine-Carboplatin Plus Necitumumab (LY3012211) in Chemotherapy-Naïve Participants With Locally Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the effectiveness and safety of gemcitabine-carboplatin plus necitumumab in chemotherapy-naïve participants with locally advanced or metastatic squamous non-small cell lung cancer.

Official Title
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A Multicenter, Phase 2 Study of Gemcitabine-Carboplatin Plus Necitumumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Locally Advanced Squamous Non-Small Cell Lung Cancer, Metastatic Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Necitumumab
* Drug: Gemcitabine
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have confirmed diagnosis of locally advanced or metastatic NSCLC in Cohort 1 and metastatic NSCLC in Cohort 2, predominantly squamous histology. Squamous NSCLC diagnosis must be confirmed by histology or cytology local pathology report. Participants in Cohort 1 are required to have epidermal growth factor receptor (EGFR) protein expressing tumor (defined by local immunohistochemistry test). This is not required for participants in Cohort 2. Measurable disease at the time of study entry as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) The participant has an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1 Have discontinued all previous treatments for cancer and recovered from the acute effects of therapy: Biologic agents (for example, antibodies) and Immunotherapy ≥4 weeks; Chest radiotherapy ≥4 weeks; Major surgery, excluding biopsy ≥4 weeks) The participant has archived tumor tissue available for biomarker analyses. Participants in Cohort 2 are required to have received 1 prior single-agent immune checkpoint inhibitor for squamous NSCLC. Exclusion Criteria: The participant has nonsquamous NSCLC The participant has received prior anticancer therapy targeting the EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor. The participant has received previous chemotherapy (including concurrent chemoradiation) for advanced NSCLC (participants who have received neo-adjuvant and/or adjuvant chemotherapy are eligible if the last administration occurred at least 1 year prior to start of therapy). The participant has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants. The participant has a bleeding tumor. The participant has a history of arterial or venous thromboembolism within 3 months prior to study enrollment. The participant has a history or evidence of current clinically-relevant coronary artery disease of current ≥ Class III as defined by Canadian Cardiovascular Society Angina Grading Scale (Campeau 1976) or congestive heart failure of current ≥ Class III as defined by the New York Heart Association. The participant has experienced myocardial infarction within 6 months prior to study enrollment.

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Necitumumab + Gemcitabine and Carboplatin<br>Predominately European sites. Gemcitabine administered intravenously (IV) and carboplatin IV plus necitumumab IV. | Drug: Necitumumab<br>* Administered IV<br>* Other names: LY3012211;Drug: Gemcitabine<br>* Administered IV<br>* Other names: LY188011;Drug: Carboplatin<br>* Administered IV<br>|
| Experimental: Cohort 2: Necitumumab + Gemcitabine and Carboplatin<br>Predominately United States sites. Gemcitabine administered IV and carboplatin IV plus necitumumab IV. | Drug: Necitumumab<br>* Administered IV<br>* Other names: LY3012211;Drug: Gemcitabine<br>* Administered IV<br>* Other names: LY188011;Drug: Carboplatin<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR): Percentage of Participants With a Complete or Partial Response |  | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 18 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Baseline to Date of Death Due to Any Cause (Approximately 24 Months) | 
| Progression Free Survival (PFS) |  | Baseline to Measured Progressive Disease or Death (Approximately 24 Months) | 
| Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response, Partial Response, and Stable Disease |  | Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Approximately 24 Months) | 
| Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab |  | Cycle 1 Day 1 through Cycle 6 Day 1 (Approximately 4 Months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer, Thoracic Neoplasms, Lung Diseases, Respiratory Tract Diseases, Respiratory Tract Neoplasms, Antineoplastic Agents, Monoclonal Antibodies