First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin

Multinational, randomized, multicenter, open-label, Phase III study of 1093 participants (age
≥ 18 years) with histologically- or cytologically-confirmed, stage IV squamous-cell NSCLC,
who have received no prior therapy for metastatic disease, will be randomized on a 1:1 basis
to receive first-line necitumumab plus chemotherapy consisting of gemcitabine and cisplatin
in study Arm A, or gemcitabine-cisplatin chemotherapy alone in study Arm B. Baseline
radiographic assessment of disease will be performed within 21 days prior to randomization
(first treatment will be administered within 7 days following randomization). Participants
will undergo radiographic assessment of disease status (computed tomography or magnetic
resonance imaging) every 6 weeks (± 3 days), until there is radiographic documentation of
progressive disease (PD). Chemotherapy will continue for a maximum of six cycles in each arm
(or until there is radiographic documentation of PD, toxicity requiring cessation, protocol
noncompliance or withdrawal of consent); participants in Arm A only will continue to receive
necitumumab until there is radiographic documentation of PD, toxicity requiring cessation,
protocol noncompliance, or withdrawal of consent.

After the end-of-study-visit (following PD), follow-up information regarding further
anticancer treatment and survival will be collected every 2 months (± 7 days). For
participants who discontinue study for reasons other than PD (eg, symptomatic deterioration),
information on disease progression will also be collected until PD is documented. Follow-up
will continue as long as the participant is alive, or until the end of the trial.

Inclusion Criteria:

- Has histologically or cytologically confirmed squamous NSCLC

- Has Stage IV disease at the time of study entry

- Measurable or nonmeasurable disease at the time of study entry as defined by the
Response Evaluation Criteria in Solid Tumors (RECIST 1.0) (participants with only
truly nonmeasurable disease are not eligible)

- Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior
chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of
alopecia)

- Has adequate hepatic function

- Has adequate renal function

- Has adequate hematologic function

- If female, is surgically sterile, postmenopausal, or compliant with a highly effective
contraceptive method (failure rate < 1%) during and for 6 months after the treatment
period (oral hormonal contraception alone is not considered highly effective and must
be used in combination with a barrier method)

- If male, the participant is surgically sterile or compliant with a highly effective
contraceptive regimen during and for 6 months after the treatment period

- Female participants of childbearing potential must have a negative serum pregnancy
test within 7 days prior to randomization

- Has archived tumor tissue available for analysis of EGFR and KRAS mutation status (by
PCR) and EGFR gene copy number (by FISH); minimum of four slides, paraffin-embedded
tissue, required

Exclusion Criteria:

- Has nonsquamous NSCLC (adenocarcinoma/large cell or other)

- Has received prior anticancer therapy with monoclonal antibodies, signal transduction
inhibitors, or any therapies targeting the EGFR, vascular endothelial growth factor
(VEGF), or VEGF receptor

- Has received previous chemotherapy for advanced NSCLC (participants who have received
adjuvant chemotherapy are eligible if the last administration of the prior adjuvant
regimen occurred at least 1 year prior to randomization)

- Has undergone major surgery or received any investigational therapy in the 4 weeks
prior to randomization

- Has undergone chest irradiation within 12 weeks prior to randomization (except
palliative irradiation of bone lesions, which is allowed)

- Has 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

- Has superior vena cava syndrome contraindicating hydration

- Has current clinically-relevant coronary artery disease or uncontrolled congestive
heart failure

- Has experienced myocardial infarction within 6 months prior to randomization

- Has an ongoing or active infection (requiring antibiotics), including active
tuberculosis or known infection with the human immunodeficiency virus

- Has a history of significant neurological or psychiatric disorders, including
dementia, seizures, or bipolar disorder

- Has any National Cancer Institute - Common Terminology Criteria for Adverse Events
(NCI-CTCAE) Version 3.0 Grade ≥ 2 peripheral neuropathy

- Has significant third space fluid retention, requiring repeated drainage

- Has any other serious uncontrolled medical disorders or psychological conditions that
would, in the opinion of the investigator, limit the participant's ability to complete
the study or sign an informed consent document

- Has a known allergy / history of hypersensitivity reaction to any of the treatment
components, including any ingredient used in the formulation of necitumumab
(IMC-11F8), or any other contraindication to one of the administered treatments

- Is pregnant or breastfeeding

- Has a known history of drug abuse

- Has a concurrent active malignancy other than adequately-treated basal cell carcinoma
of the skin or preinvasive carcinoma of the cervix. A participant with previous
history of malignancy other than NSCLC is eligible, provided that he/she has been free
of disease for ≥ 3 years