A Study of Ramucirumab Plus Pembrolizumab in Participants With Gastric or GEJ Adenocarcinoma, NSCLC, Transitional Cell Carcinoma of the Urothelium, or Biliary Tract Cancer

DLT is defined as an Adverse Event (AE) that is likely related to study medication or combination,and fulfills any one of following criteria:Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0): Grade (Gr) 3 and 4 nonlaboratory toxicity (tox),Any Gr 3 or 4 laboratory value if medical intervention is required to treat participant (pt) or abnormality persists for \>1 week;Hematologic tox:Gr 4 toxicity lasting ≥ 7 days,or Gr 3 thrombocytopenia if associated with bleeding and requires platelet transfusion,or Febrile neutropenia Gr 3 or Gr 4;GR 5 tox (death);Any toxicity that is possibly related to study treatment that requires withdrawal of pt from study during Cycle 1,A delay of \> 14 days due to persistent Grade ≥ 2 toxicities in initiating Cycle 2,with exception of Grade 2 fatigue;Any infusion or hypersensitivity reactions are NOT a DLT. A summary of other nonserious AEs and all Serious AEs,regardless of causality is located in Reported Adverse Event section.

Time frame: Cycle 1 (21 Days)

Population: All enrolled participants who received at least one dose of the study drug in dose escalation phase and experienced a DLT. DLT was assessed in Phase 1a of Cohorts A and C during Cycle 1.

The duration of response is defined only for responders (patients with a confirmed CR or PR). It is 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 responder is not known to have died or have objective progression as of the data inclusion cutoff date, DoR will be censored at the date of the last complete objective progression-free disease assessment (CR or PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause.

Time frame: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up to 24 Months)

Population: All enrolled participants who received at least one dose of the study drug. Per Protocol, Cohort A and B participants \[Gastric-GEJ cancer (Second-Third L)\] were combined and outcome data was analyzed under a single arm (Cohort A and B).

The OS time is defined as the time from baseline to the date of death from any cause. If a participant is not known to have died on or before the date of data cut-off, OS data will be censored on the last date (on or before the cut-off date) the participant was known to be alive.

Time frame: Baseline to Death from Any Cause (Up to 24 Months)

Population: All enrolled participants who received at least one dose of the study drug. Censored participants: Cohort A and B = 8; Cohort A1 = 8; Cohort A2 = 12; Cohort C = 12; Cohort D = 6 and Cohort E = 18. Per Protocol, Cohort A and B participants \[Gastric-GEJ cancer (Second-Third L)\] were combined and outcome data was analyzed under a single arm (Cohort A and B).

Overall response rate is the best response of complete response (CR) or partial response (PR) as classified by the independent central review according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. PR is 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. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants per cohort with at least 1 measurable lesion, multiplied by 100. Progressive Disease (PD) was 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.

Time frame: Baseline to Measured Progressive Disease (Up to 24 Months)

Population: All enrolled participants who received at least one dose of the study drug. Per Protocol, Cohort A and B participants \[Gastric-GEJ cancer (Second-Third L)\] were combined and outcome data was analyzed under a single arm (Cohort A and B).

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. Participants who do not have any postbaseline tumor response assessments for any reason were considered.

Time frame: Baseline to Measured Progressive Disease (Up to 24 Months)

Population: All enrolled participants who received at least one dose of the study drug. Per Protocol, Cohort A and B participants \[Gastric-GEJ cancer (Second-Third L)\] were combined and outcome data was analyzed under a single arm (Cohort A and B).

PK: Cmin of Ramucirumab following administration every 3 weeks.

Time frame: Phase 1a (Gastric-GEJ or BTC participants (pts)): Week (Wk) 1, 3, 6 and 9; Phase 1a (Gastric, NSCLC, or urothelial pts): Wk 3, 6, 9 and 12; Cohort A, A1, A2: Wk 1, 3, 6, 9, 12, 18, 19 and 24; Cohort B,C,D,E: Wk 3, 6, 9, 12, 18, 19 and 24

Population: All enrolled participants who received at least one dose of the study drug and had evaluable ramucirumab PK data. PK was assessed both in Phase 1a and 1b as per protocol analysis.

PFS is defined as the time from the date of first study treatment until the date of the first observed radiographically documented progressive disease (PD) or death due to any cause, whichever is earlier. PD was determined using RECIST criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion.

Time frame: Baseline to PD or Death of Any Cause (Up to 24 Months)

Population: All enrolled participants who received at least one dose of the study drug. Censored participants: Cohort A and B = 3; Cohort A1 = 4; Cohort A2 = 8; Cohort C = 10; Cohort D = 3 and Cohort E = 13. Per Protocol, Cohort A and B participants \[Gastric-GEJ cancer (Second-Third L)\] were combined and outcome data was analyzed under a single arm (Cohort A and B).

TTR is defined as the time from the date of first study treatment until the first evidence of a confirmed CR or PR.

Time frame: Baseline to Date of CR or PR (Up to 24 Months)

Population: All enrolled participants who received at least one dose of the study drug. Per Protocol, Cohort A and B participants \[Gastric-GEJ cancer (Second-Third L)\] were combined and outcome data was analyzed under a single arm (Cohort A and B).