A Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab in the First-Line Treatment of Participants With Squamous Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to see how participants with late stage lung cancer do on gemcitabine-cisplatin chemotherapy plus necitumumab. The study will also see how safe the drugs are in combination and to see how long the medicine stays in the body. The study will last approximately 2 years.

Official Title
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A Single-Arm, Multicenter, Open-Label, Phase 2 Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Non-small Cell Lung Cancer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed squamous Non-small Cell Lung Cancer (NSCLC) Stage IV disease at time of study entry based on American Joint Committee on Cancer 7th edition Measurable disease at time of study entry as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 Required to have a performance status (PS) 0-1 Exclusion Criteria: Nonsquamous NSCLC Prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor Previous chemotherapy for NSCLC Major surgery or received any investigational therapy in the 4 weeks prior to study enrollment Chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed) Brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants (participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible)

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: Gemcitabine + Cisplatin + Necitumumab<br>Necitumumab administered intravenously (IV) 800 milligram (mg) on Days 1 and 8 of each 3-week cycle. Gemcitabine administered IV at 1250 milligram per square meter (mg/m^2) on Days 1 and 8 of each 3 week cycle for a maximum of 6 cycles. Cisplatin administered IV at 75 mg/m^2 on Day 1 of each 3 week cycle for a maximum of 6 cycles. | Drug: Necitumumab<br>* Administered IV<br>* Other names: Portrazza®;Drug: Gemcitabine<br>* Administered IV<br>* Other names: LY188011;Drug: Cisplatin<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR) | ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.1, PR defined as a >30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. Percentage of participants was calculated as: total number of participants with a best tumor response of PR or CR among participants counted in the denominator/total number of participants treated with any amount of study drug, who has a complete radiographic assessment at baseline, and who has at least 1 complete radiographic assessment at postbaseline x 100%. | Baseline to Measured Progressive Disease (up to 17 Months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Overall survival (OS) duration is defined from the date of first dose of study drug to the date of death from any cause. OS was estimated by the Kaplan-Meier method. For participants who were not known to have died as of the data cut-off date, OS was censored at the date of last contact prior to the data cutoff date. | Baseline to Death from Any Cause (up to 17 Months) | 
| Progression Free Survival (PFS) | PFS is defined as the time from the date of first dose of study drug until objective progressive disease (PD) or death for any cause. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions was also considered progression. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last complete radiographic assessment. | Baseline to Measured Progressive Disease or Death from Any Cause (up to 17 Months) | 
| Number of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) [Disease Control Rate (DCR)] | DCR is best overall response of SD, PR or CR. According to RECIST v1.1, PR defined as a ≥30% decrease in the sum of the longest diameters (LD) of the target lesions, taking as reference the baseline sum of the LD; CR was defined as the disappearance of all target and non-target lesions. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. Percentage of participants who achieved disease control = (those participants counted in the denominator with a best tumor response of SD, PR, or CR)/(the same denominator as for ORR)*100. | Baseline to Measured Progressive Disease or Participants Stops Study (up to 17 Months) | 
| Percent Change in Tumor Size (CTS) | CTS is defined as maximum percent improvement from baseline in the sum of target lesions. | Baseline until Measured Progressive Disease (up to 17 Months) | 
| Pharmacokinetics (PK): Minimum (Cmin) Maximum Concentration (Cmax) of Necitumumab | Pre-infusion Minimum Concentration (Cmin) and post-infusion (Cmax) necitumumab serum concentration | Predose Cycle 1 Day 8; Cycle 2 through 6 Day 1; End of Infusion (EOI) Cycle 1, 3, 5 Day 1 | 
| Number of Participants With Anti-Necitumumab Antibodies | A participant was considered to have an anti-necitumumab antibody response if anti-drug antibodies (ADA) were detected at any time point. Treatment emergent antibodies were defined as any anti-necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer. | Baseline up to 30 Days Post Last Infusion (up to 17 Months) |