Clinical Trials

Inclusion Criteria:

• Age ≥18 years;
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• Life expectancy ≥3 months, as determined by the investigator;
• Histologically or cytologically confirmed locally advanced unresectable or metastatic adenocarcinoma of gastric or gastroesophageal junction; (for the 1L Cohort: no prior systemic therapy for the locally advanced or metastatic disease; for the 2L Cohort: disease progression during or following a first-line platinum-containing or fluoropyrimidine-containing chemotherapy regimen);
• Only for the 1L Cohort: human epidermal growth factor receptor 2 (HER2)-negative tumors;
• Measurable disease (at least one target lesion) according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1);
• Adequate hematologic and end organ function based on laboratory results obtained within 14 days prior to initiation of study treatment;
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures as outlined for each specific treatment arm;
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm.

Exclusion Criteria:

Exclusion criteria for the 2L Cohort:

• Urinary protein is > 1 + on dipstick and the required following 24-hour urine collection shows urinary protein > 2000 mg;
• Serious or non-healing wound, peptic ulcer, or bone fracture within 28 days prior to initiation of study treatment;
• History of gastrointestinal perforation and/or fistulae within 6 months prior to initiation of study treatment;
• Presence of a bowel obstruction, history or presence of inflammatory enteropathy, or extensive intestinal resection, Crohn disease, ulcerative colitis, or chronic diarrhea;
• Uncontrolled arterial hypertension ≥150/ ≥90 millimeter of mercury (mmHg) despite standard medical management;
• Chronic therapy with non-steroidal anti-inflammatory agents or other anti-platelet agents.

Exclusion Criteria:

• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy;
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;
• History of leptomeningeal disease;
• Active or history of autoimmune disease or immune deficiency;
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan;
• Positive test for human immunodeficiency virus (HIV) at screening;
• Active hepatitis B virus (HBV) or hepatitis C (HCV) infection;
• Severe infection within 4 weeks prior to initiation of study treatment;
• Significant cardiovascular disease;
• Significant bleeding disorder;
• Prior allogeneic stem cell or solid organ transplantation;
• Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study;
• Treatment with anticoagulation with warfarin, low-molecular-weight heparin, or similar agents for therapeutic purposes;
• History of malignancy other than gastric or gastroesophageal junction carcinoma within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death;
• Known allergy or hypersensitivity to any of the study drugs or their excipients.