A Study of Ramucirumab in Participants With Gastric or Gastroesophageal Junction Adenocarcinoma

PFS is defined as the time from the date of randomization until the date of objectively determined progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause, whichever is first. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 millimeter (mm) or the appearance of ≥1 new lesions was progression. Participants who did not progress, were lost to follow-up were censored at the day of their last adequate tumor assessment.

Time frame: Randomization to Radiographic Documentation of Progression or Death Due to Any Cause (Up to 25 Months)

Population: All randomized participants who received any quantity of study drug in Part A. Censored participants: Ramucirumab + S-1 + Oxaliplatin = 23; Placebo + S-1 + Oxaliplatin = 19.

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the 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 PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm or the appearance of ≥1 new lesions was progression.

Time frame: Randomization to Disease Progression (Up to 25 Months)

Population: All randomized participants who received any quantity of study drug in Part A with measurable disease.

Participant is considered as treatment emergent anti-drug antibody (TE ADA) positive if the participant has at least one post baseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the participant is TE ADA+ if there is at least one post baseline result of ADA Present with titer \>= 20.

Time frame: Baseline through 25 months

Population: All randomized participants who received any quantity of study drug in part A and had at least one baseline \& post baseline antibody (ADA) measurement.

Overall survival is defined as time from the date of randomization to the date of death from any cause. If the patient was alive at the cut-off for analysis (or lost to follow-up), OS data were censored for analysis on the last date the patient was known to be alive.

Time frame: Randomization to Death Due to Any Cause (Up to 31 Months)

Population: All randomized participants who received at least one dose of study drug. Censored participants: Ramucirumab + S-1 + Oxaliplatin = 27; Placebo + S-1 + Oxaliplatin = 30.

The ORR is the number of all participants with Partial Response (PR) or Complete Response (CR) according to RECIST v1.1 from the start of the treatment until disease progression/recurrence. CR is defined as the disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to \<10 mm. PR is defined as ≥30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter. Disease progression is defined as ≥20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (included baseline sum if that was the smallest on study); sum must have demonstrated an absolute increase of ≥5 mm or the appearance of ≥1 new lesions was progression.

Time frame: Randomization to Disease Progression (Up to 25 Months)

Population: All randomized participants who received any quantity of study drug in Part A with measurable disease.

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Ramucirumab in Part A.

Time frame: Cycle 1 Day 1 & 8 Predose, Cycle 2 Day 1 Predose, Cycle 3 Day 1 Predose, Cycle 5 Day 1 Predose, Cycle 9 Day 1 Predose

Population: All randomized participants who received at least one dose of ramucirumab in part A and had evaluable PK samples.

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

Time frame: Cycle 1 Day 1 predose, Cycle 2 Day 1 predose

Population: All randomized participants who received at least one dose of ramucirumab in part B and had evaluable PK samples.

Progression-free survival 2 (PFS2) is defined as the time from the date of randomization to second disease progression (defined as the date of first tumor assessment observing PD defined by RECIST v.1.1, after the start of second-line therapy using the last tumor assessment before starting the second-line therapy (RAM+PTX) as the baseline assessment), or death of any cause, whichever occurs first. If the second-line therapy was not started, the OS will be substituted for PFS2. If a post-discontinuation therapy was started before observing PD after the start of second-line therapy. PD is 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 1 or more new lesions. PFS2 will be censored at the date of the last adequate tumor assessment on or before staring the post-discontinuation therapy.

Time frame: Randomization to Second Radiographic Documentation of Progression or Death Due to Any Cause (Up to 31 Months)

Population: All randomized participants who received any quantity of study drug. Censored participants: Ramucirumab + S-1 + Oxaliplatin = 26; Placebo + S-1 + Oxaliplatin = 26.