Stage IV squamous NSCLC first line treatment.

The primary objective of this study is to estimate the best objective response rates (ORR; complete response [CR] + partial response [PR]) associated with gemcitabine-cisplatin plus necitumumab in chemotherapy-naïve patients with Stage IV squamous cell NSCLC. The secondary objectives of this study are: • to evaluate OS, PFS, DCR, and CTS; • to evaluate the safety profile of necitumumab in combination with gemcitabine-cisplatin chemotherapy; • to characterize pharmacokinetics of necitumumab; and • to determine the immunogenicity of necitumumab.

Necitumumab

Necitumumab

Vial

800

Efficacy: For these definitions, the date of study enrollment is the date of first dose of study drug (necitumumab,
gemcitabine, and/or cisplatin)

• Tumor response will be assessed according to RECIST 1.1 every 6 weeks (±3 days) by the investigator with confirmatory assessment for patients with an objective assessment of PR or CR obtained at the next routine scheduled imaging time point (that is, after 6 weeks ±3 days).
• OS is defined as the time from the date of study enrollment until the date of death.
• PFS is defined as the time from the date of study enrollment until the date of
radiographically documented PD or death due to any cause, whichever comes first.
• DCR is defined as best tumor response of PR, CR, or SD.
• CTS is defined as the maximum percent improvement in the sum of target lesions.

Safety: The safety of necitumumab in combination with gemcitabine-cisplatin chemotherapy will be assessed by reported SAEs, AEs, vital sign measurements, electrocardiogram results, and laboratory analyses. The National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.0, will serve as the reference document for choosing appropriate terminology for, and grading the severity of, all AEs and other
symptoms. This collection is in addition to the verbatim text used to describe the AE. In addition to collecting the AE verbatim, the CTCAE term, and the CTCAE severity grade, AE verbatim text will also be mapped by the Sponsor or designee to corresponding terminology within the Medical Dictionary for Regulatory Activities
(MedDRA™) dictionary.

Pharmacokinetics: Blood for determination of serum concentrations of necitumumab will be drawn from patients at the following time points: prior to the first infusion on Day 1 of Cycles 1, 2, 3, 4, 5, and 6 and Day 8 of Cycle 1; at the end of infusion on Day 1 of Cycles 1, 3, and 5; at the 30-day safety follow-up visit; and in the setting of any hypersensitivity/infusion-related reaction.

Immunogenicity: Analysis of antibodies against necitumumab (immunogenicity) will be performed based on blood drawn from patients at the following time points: prior to the initial necitumumab infusion on Day 1 of Cycles 1, 2, 4, and 6; at the 30-day safety follow-up visit; and in the setting of any hypersensitivity/infusion-related reaction.

Key Inclusion Criteria
• Histologically or cytologically confirmed squamous NSCLC
• Stage IV disease at time of study entry based on AJCC 7th edition
• Measurable disease at time of study entry as defined by RECIST 1.1

Key Exclusion Criteria
• Nonsquamous NSCLC
• Prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the 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 (patients who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible)