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

OS is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated using the Kaplan-Meier method.

Time frame: Randomization to Death from Any Cause (Up to 31.6 Months)

Population: All randomized participants. Censored participants: Necitumumab + Pemetrexed + Cisplatin =79, Pemetrexed + Cisplatin=72

EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses participants with a low EGFR expression defined by a H-score cutoff value of \< 200 and participants with a high EGFR expression defined by a H-score of cutoff value of \>=200.

Time frame: Baseline

Population: Translational research population included all participants who: (1) received at least one dose of study drug; (2) had a valid non-missing result for EGFR H-Score; and (3) were enrolled for more than 2 cycles prior to the decision to terminate enrollment.

The EQ-5D is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and major problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United Kingdom (UK) population-based algorithm. The possible values for the Index Score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension).

Time frame: Baseline, Cycle 6 (Cycle = 3 weeks)

Population: All randomized participants who had evaluable baseline and postbaseline EQ-5D data.

The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms \[loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain\] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. Scores for each of the reported categories ranged from 0 (for best outcome) to 100 (for worst outcome). The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively.

Time frame: Baseline, Cycle 6 (Cycle =3 Weeks)

Population: All randomized participants who had evaluable baseline and postbaseline LCSS data.

A participant was considered to have an anti-Necitumumab antibody response if anti-drug antibodies (ADA) were confirmed positive. Treatment emergent antibodies were defined as any anti-Necitumumab antibody titer equal to or greater than 4-fold the participant's baseline titer.

Time frame: Baseline to Study Completion (Up to 31.6 Months)

Population: All randomized participants who received at least one dose of necitumumab and had evaluable antibody data.

ORR is confirmed best overall tumor response of CR or PR. According to RECIST v1.0, CR was defined as the disappearance of all target and non-target lesions; 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. Percentage of participants was calculated as: (total number of participants with CR or PR from start of the treatment until disease progression or recurrence)/total number of participants treated) \* 100.

Time frame: Baseline to Measured Progressive Disease (Up to 30.4 Months)

Population: All randomized participants.

EGFR IHC H-score = weighted sum of % 1+ cells, twice % 2+ cells, and three times % 3+ cells. IHC H-score criteria assesses participants with a low EGFR expression defined by a H-score cutoff value of \< 200 and participants with a high EGFR expression defined by a H-score of cutoff value of \>=200.

Time frame: Baseline

Population: Translational research population included all participants who: (1) received at least one dose of study drug; (2) had a valid non-missing result for EGFR H-Score; and (3) were enrolled for more than 2 cycles prior to the decision to terminate enrollment

Time frame: Predose Day 1 of Cycle 2,3,4,5 and 6 Prior to Necitumumab Infusion, Up to 23 Weeks

Population: Participants who were randomized to necitumumab and had evaluable PK data.

PFS is defined as the time from randomization until the first radiographic documentation of measured progressive disease as defined by RECIST (Version 1.0), or death from any cause. Participants who die without a reported prior progression will be considered to have progressed on the day of their death. Participants who did not progress or were lost to follow-up were censored at the day of their last radiographic tumor assessment. If no baseline or postbaseline radiologic assessment was available, the participant was censored at the date of randomization. If death or PD occurs after two or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits.

Time frame: Randomization to Measured Progressive Disease or Death from Any Cause (Up to 30.4 Months)

Population: All randomized participants. Censored participants: Necitumumab + Pemetrexed + Cisplatin=84, Pemetrexed + Cisplatin=79

TTF was defined as the time from study enrollment/randomization to the first observation of measured progressive disease, death from any cause, or early discontinuation of treatment or initiation of new anti-cancer therapies. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive Disease (PD) was defined as having at least a 20% increase in sum of longest diameter of target lesions. Time to treatment failure was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed.

Time frame: Randomization to Measured Progressive Disease, Death from Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 30.4 Months)

Population: All randomized participants. Censored participants: Necitumumab + Pemetrexed + Cisplatin = 10, Pemetrexed + Cisplatin = 13