A Study of Paclitaxel With or Without Ramucirumab (IMC-1211B) in Metastatic Gastric Adenocarcinoma

OS time was measured from date of randomization to date of death from any cause. Participants who were not known to have died on or before the date of data cut-off, OS data was censored on the last date (on or before the cut-off date) the participant was known to be alive.

Time frame: Randomization up to 27.5 months

Population: All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =74, Placebo plus Paclitaxel =75.

BOR was defined as the best response across all time points from randomization until radiologically confirmed PD using RECIST, v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. PD was defined as having a ≥20% increase in sum of LD of target lesions and ≥5 mm increase above nadir. SD was defined as small changes that did not meet above criteria.

Time frame: Randomization up to 22.2 months

Population: All participants according to the treatment group to which they were randomized.

EORTC QLQ-C30 v3.0 is a 30-item, self-administered questionnaire with multidimensional scales assessing 15 domains (5 functional domains \[physical, role, cognitive, emotional, and social\], 9 symptom scales \[fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties\] and global health status scale). 28 questions assessed on a 1 (not at all) to 4 (very much) scale and the remaining 2 questions used a 1 (poor) to 7 (excellent) scale. A linear transformation was applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For the functional domains and global health status scale, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.

Time frame: Baseline, end of therapy (up to 103 weeks)

Population: All participants according to the treatment group to which they were randomized with baseline and end of treatment Global Health Status observations.

The EQ-5D is a generic, multidimensional, health status instrument. The profile allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood using a 3-level scale \[1 (no problem), 2 (some problems), and 3 (major problems)\]. These combinations of responses 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). A negative change indicated a worsening of the participant's health status.

Time frame: Baseline, end of therapy (up to 103 weeks)

Population: All participants according to the treatment group to which they were randomized with baseline and end of treatment EQ-5D observations.

Time frame: Cycle 2, Day 15 1 hour post end of infusion (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.

Time frame: Cycle 4, Day 1, 1 hour post end of infusion (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.

Time frame: Cycle 2, Day 15 (28-day cycle)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmin observations at specific timepoint.

Time frame: Cycle 4, Day 1 (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmin observations at specific timepoint.

Time frame: Cycle 1, Day 1, 1 hour post end of infusion (28-day cycles)

Population: All participants who received Ramucirumab (IMC-1121B) plus Paclitaxel and had Cmax observations at specific timepoint.

This outcome measure was included in error as the time point was before ramucirumab (IMC-1211B) was administered. Cmin was not analyzed.

Time frame: Cycle 1, Day 1 predose (28-day cycles)

Population: Zero participants were analyzed.

Participants who developed treatment-emergent antibody responses to Ramucirumab (IMC-1121B) after baseline.

Time frame: Prior to and after ramucirumab (IMC-1121B) infusion: Day 1 Cycles 1, 2 and 3 (28-day cycles) Doses 1, 4, 7 and 30-37 days after last dose of study therapy up to 103 weeks

Population: All participants according to the treatment group to which they were randomized and received at least 1 dose of study drug with anti-ramucirumab antibodies.

ORR was the percentage of participants who had CR or PR defined using RECIST v1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm and normalization of tumor marker level of non-target lesions. PR was defined as having a ≥30% decrease in sum of LD of target lesions. Percentage of participants calculated as: (number of participants with CR + PR)/(total number of participants)\*100.

Time frame: Randomization up to 22.2 months

Population: All participants according to the treatment group to which they were randomized.

PFS was measured from date of randomization to first radiographically documented progressive disease (PD) or death due to any cause. PD defined using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of at least 5 mm. Participants who had no baseline or post baseline radiological tumor assessment were censored at date of randomization. Participants who had no tumor progression or death within 2 scan intervals following the last assessment were censored at the date of last radiographic tumor assessment. Participants who began new anticancer treatment and had no tumor progression were censored at date of assessment prior to initiation of new therapy. Participants lost to follow-up or withdrew consent were censored at the date of their last assessment.

Time frame: Randomization up to 22.2 months

Population: All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =51, Placebo plus Paclitaxel =39.

TTP was defined as the time from randomization until date of radiographic progression using RECIST v1.1 criteria. PD was defined as having a ≥20% increase in sum of longest diameter (LD) of target lesions and at minimum 5 millimeters (mm) increase above nadir. Participants who did not progress or were lost to follow-up were censored at the date of last tumor assessment. Participants who had no baseline tumor assessment or no post baseline assessment and no death reported with 2 scan intervals post randomization were censored at date of randomization. Participants with no progression and not died within 2 scan intervals after last assessment were censored at date of last tumor assessment. Participants with no post baseline assessment or tumor progression but death reported within 2 scan intervals after randomization were censored at date of death.

Time frame: Baseline up to 22.2 months

Population: All participants according to the treatment group to which they were randomized. Participants censored: Ramucirumab (IMC-1211B) plus Paclitaxel =107, Placebo plus Paclitaxel =94.

Participants who died or who had clinically significant events defined as serious AEs (SAEs) and other non-serious AEs (regardless of causality). A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.

Time frame: Baseline up to 103 weeks and within 30 days of last dose of study drug

Population: All randomized participants who received at least 1 dose of study drug and based on the treatment each participant received.