A Dose Limiting Toxicity (DLT) was defined as one of the following Adverse Events (AE) that is likely related to the study drug or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0:

1. Any nonhematologic Grade ≥3 toxicity, except for toxicities such as liver or renal function abnormality, skin rash that resolves with appropriate therapy, transient hypersensitivity and injection site reactions, myalgia, fatigue, constipation, electrolyte imbalance, nausea, vomiting, diarrhea

2. Hematologic toxicity was considered a DLT as the following:

   1. Grade 4 toxicity lasting ≥7 days, or
   2. Grade 3 or 4 thrombocytopenia if associated with bleeding or requires platelet transfusion, or
   3. Febrile neutropenia

3. Death if considered related to study treatment

4. Any other significant toxicity deemed by the primary investigator and Lilly clinical research personnel to be dose limiting

Arm A: participants who either completed the first 2 cycles of treatment or discontinued from study treatment or study participation Arm B: participants who either completed the first cycle of treatment or discontinued from study treatment or study participation

Cmin was the concentration of study drug in the blood immediately before the next dose was administered.

All enrolled participants who received at least one dose of ramucirumab and had evaluable PK data.

Cmin was the concentration of study drug in the blood immediately before the next dose was administered.

All enrolled participants who received at least one dose of necitumumab and had evaluable PK data.

ORR was the best overall response of complete response (CR) or partial response (PR) as classified by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). CR was a disappearance of all target and non-target lesions and normalization of tumor marker level. PR was an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions.

All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug. Per Protocol, the outcomes for a combination of ramucirumab and osimertinib were analyzed under a single arm (Arm A/Cohort A), as Cohort A is an extension of Arm A.

DCR was the best overall response of CR, PR, or SD as defined by RECIST v1.1. CR was defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or one or more new lesions.

All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug. Per Protocol, the outcomes for a combination of ramucirumab and osimertinib were analyzed under a single arm (Arm A/Cohort A), as Cohort A is an extension of Arm A.

Duration of Response (DoR) was defined only for participants with a confirmed CR or PR. It was measured from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever is earlier. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date, DOR was censored at the date of the last complete objective progression-free disease assessment.

All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug with a confirmed CR or PR (including censored). Number of participants censored = 7.

Progression-free survival (PFS) was the time from the date of first study treatment until the date of radiographic documentation of progression (as defined by RECIST v. 1.1) based on investigator assessment or the date of death due to any cause, whichever was earlier. If a participant did not have a complete baseline disease assessment, then the PFS time was censored at the enrollment date, regardless of whether or not objectively determined disease progression or death was observed for the participant; otherwise, if a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last complete objective progression-free disease assessment date.

All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug (including censored). Number of participants censored = 7.

OS was date of first study treatment until death due to any cause. If the participant was alive at the data inclusion cutoff date for the analysis (or was lost to follow-up), OS was censored on the last date the participant was known to be alive.

All enrolled participants from the ramucirumab + osimertinib arms who received at least one dose of study drug (including censored). Number of participants censored = 13.