First-line Treatment of Patients With Stage IV Nonsquamous Non-Small Cell Lung Cancer With Necitumumab (IMC-11F8) and Pemetrexed-Cisplatin

Multinational, randomized, multicenter, open-label Phase 3 study of 633 participants with
advanced, nonsquamous (Stage IV) NSCLC. Participants will be randomized on a 1:1 basis to
receive first-line necitumumab plus chemotherapy consisting of pemetrexed and cisplatin in
study Arm A, or first-line pemetrexed-cisplatin chemotherapy alone in 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 (computed tomography or magnetic resonance
imaging) of disease status 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 nonsquamous (adenocarcinoma/large cell
or other) non small cell lung cancer

- Has Stage IV disease at the time of study entry

- Measurable or nonmeasurable disease (as defined by the Response Evaluation Criteria in
Solid Tumors RECIST 1.0) at the time of study entry (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 an Eastern Cooperative Oncology Group performance status score of 0-2

- 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 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 participants 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

Exclusion Criteria:

- Has squamous non small cell lung cancer

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

- 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)

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

- 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, potentially precluding protocol compliance

- Has 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 The participant has a known allergy /
history of hypersensitivity reaction to any of the treatment components, including any
ingredient used in the formulation of 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