A Study of Ramucirumab (LY3009806) in Combination With Erlotinib in Previously Untreated Participants With EGFR Mutation-Positive Metastatic NSCLC (RELAY)

A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section.

Time frame: Cycle 1 Day 1 through End of Study (Up To 3 Years)

Population: All randomized participants who received at least one dose of study drug.

PFS is defined as the time from the date of randomization to the date of radiographically documented progressive disease (PD) based on investigator assessment, or the date of death due to any cause, whichever is first assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

Time frame: Randomization to Measured Progressive Disease or Death from Any Cause (Up To 37 Months)

Population: Part B: All randomized participants grouped according to their assigned treatment at randomization. Censored participants were: Part B: Ramucirumab+ Erlotinib= 102 and Part B: Placebo+ Erlotinib= 67. Per protocol, Part A did not evaluate efficacy.

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 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-millimeter (mm) lines. A higher score for any item represented a higher level of symptoms/problems. The LCSS total score was defined as the mean of all 9 items. Average symptom burden index (ASBI) was calculated as the mean of the six symptom-specific questions from the LCSS. Potential scores range from 0 (for best outcome) to 100 (for worst outcome).

Time frame: Baseline, End of Study (Up To 37 Months)

Population: Part B: All randomized participants who completed the LCSS at baseline and at least once post-baseline. Per protocol, Part A did not evaluate efficacy.

The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.

Time frame: Baseline, Cycle 40 (each cycle is 2 weeks)

Population: Part B: All randomized participants who completed the EQ-5D-5L at baseline and at least once post-baseline. Per protocol, Part A did not evaluate efficacy.

The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.

Time frame: Baseline, Cycle 10 (each cycle is 2 weeks)

Population: Part B: All randomized participants who completed the EQ-5D-5L at baseline and at least once post-baseline. Per protocol, Part A did not evaluate efficacy.

The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It consists of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, and extreme problems/unable to), ranging from 1 to 5 (good to bad). Dimension responses were converted to an index score using UK weights. The index scores were anchored on full health (1.0) to dead (0) with negative values assigned to health states considered worse than death.

Time frame: Baseline, Cycle 28 (each cycle is 2 weeks)

Population: Part B: All randomized participants who completed the EQ-5D-5L at baseline and at least once post-baseline. Per protocol, Part A did not evaluate efficacy.

DoR was defined as the date of first documented CR or PR (responder) to the date of progressive disease or the date of death due to any cause, whichever was earlier. If a responder was not known to have died or have progressive disease, then the participant was censored at the date of last evaluable tumor assessment.CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

Time frame: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up To 37 Months)

Population: Part B: All randomized participants grouped according to their assigned treatment at randomization that had a response (CR or PR). Per protocol, Part A did not evaluate efficacy.

Part B: Number of Participants With Anti-Ramucirumab Antibodies.

Time frame: Cycle 1 Predose through Follow-up (Up To 37 Months)

Population: All participants who received at least one dose of study drug. Per protocol, Part A did not evaluate Anti-Ramucirumab Antibodies .

OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who was not known to have died as of the data-inclusion cutoff date for a particular analysis,OS was censored for that analysis at the date of last contact prior to the data-inclusion cutoff date (contacts considered in the determination of last contact date include adverse event (AE) date, lesion assessment date, visit date, and last known alive date).

Time frame: Randomization to Date of Death from Any Cause (Up To 37 Months)

Population: Part B: All randomized participants grouped according to their assigned treatment at randomization. Censored participants were: Part B: Ramucirumab+ Erlotinib= 187 and Part B: Placebo+ Erlotinib= 183. Per protocol, Part A did not evaluate efficacy.

ORR was defined as the percentage of randomized participants achieving a best overall response of partial response (PR) or complete response (CR) assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions. PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of 1 or more new lesions is also considered progression.

Time frame: Randomization to Progressive Disease (Up To 37 Months)

Population: Part B: All randomized participants grouped according to their assigned treatment at randomization. Per protocol, Part A did not evaluate efficacy.

DCR was defined as the percentage of randomized participants achieving a best overall response of CR,PR, or stable disease(SD) assessed via Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1. CR was defined as the disappearance of all lesions,pathological lymph node reduction in short axis to \<10 mm, and normalization of tumor marker levels of non-target lesions.PR was at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters.SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease(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 relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of 1 or more new lesions is also considered progression.

Time frame: Randomization to Progressive Disease (Up To 37 Months)

Population: Part B: All randomized participants grouped according to their assigned treatment at randomization. Per protocol, Part A did not evaluate efficacy.

Part B: Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab

Time frame: Cycle 2 Day 1: Predose; Cycle 4 Day 1: Predose; Cycle 7 Day 1: Predose; Cycle 14 Day 1

Population: Part B participants who received at least one dose of Ramucirumab+ Erlotinib who had evaluable PK data. Per protocol, Part A did not evaluate PK.