Oxaliplatin and Liposomal Irinotecan (Plus Trastuzumab for HER2-positive Disease) in Advanced Esophageal and Gastric Adenocarcinoma

Exclusion Criteria

• •Known hypersensitivity to 5-FU, oxaliplatin or other platinum agents, or any of the components of nal-IRI and other liposomal products.
• •Known dihydropyrimidine dehydrogenase (DPD) deficiency (testing not required prior to enrollment).
• •Other active malignancy requiring treatment within the last 2 years. Exceptions include subjects with non-melanoma skin cancer, non-invasive/in situ cancer or low-risk prostate cancer requiring hormonal therapy only.
• •Current therapy with other investigational agents or participation in another clinical study (supportive care and nontherapeutic trial participation allowed if not receiving an investigational drug). Participants may participate in prescreening for other therapeutic trials (prescreening of biologic sample for specific mutations, receptors, etc.)
• •Major surgery within 28 days or minor surgery within 14 days of the start of the study treatment, except for tumor biopsy or placement of central infusion device (port placement).
• •Radiotherapy less than 7 days prior to the start of the study treatment
• •Participants who receive nivolumab or pembrolizumab in addition to chemotherapy should not have any contraindications to immune checkpoint inhibitors and should not have received immunotherapy agents for the treatment of EGA prior to study enrollment.
• •* Participants must not have active autoimmune disease that has required systemic treatment in the past 2 years. Participants are permitted to receive immunotherapy l if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
• •* Participants must not have a condition requiring systemic treatment with either corticosteroids (\>10 mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of study immunotherapy administration. Inhaled or topical steroids and adrenal replacement doses (≤10 mg/day prednisone equivalent) are permitted. Participants with prior immune mediated adverse events related to immunotherapy that resulted in permanent treatment discontinuation with these agents.
• •Psychological, familial, or sociological condition potentially hampering compliance with the study protocol and follow-up schedule.
• •Active infection requiring systemic therapy.
• •Pregnant or breastfeeding.
• •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
• •Severe arterial thromboembolic events (myocardial infarction, unstable angina pectoris, stroke) less than 6 months before inclusion.
• •NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure.
• •Known history of Human Immunodeficiency Virus (HIV).