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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Written informed consent and HIPAA authorization for release of personal health information.
• NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Histological or cytological confirmed locally advanced or metastatic EGA. Known HER2 status prior to treatment initiation required. Known PDL1 CPS status prior to treatment initiation.
• Measurable disease according to RECIST v1.1.
• No prior lines of systemic therapy for advanced disease.
• Participants who had received neoadjuvant or adjuvant therapy or definitive chemoradiation will be allowed to participate if recurrence occurred 6 months or longer from the completion of all prior treatments.
• Demonstrate adequate organ function as defined below; all screening labs to be obtained within 14 days prior to registration
• Absolute Neutrophil Count (ANC) ≥1,500 /μl without the use of hematopoietic growth factors
• Hemoglobin (Hgb) ≥8 g/dL (blood transfusions are permitted for participants with hemoglobin levels below 8 g/dL)
• Platelets ≥100,000 /μl
• Serum creatinine ≤1.5 X upper limit of normal (ULN) OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl). CrCl calculation using the Cockcroft-Gault formula. ≥50 mL/min for participants with creatinine levels > 1.5 X institutional ULN
• Bilirubin within normal range for the institution (biliary drainage is allowed for biliary obstruction); abnormal bilirubin (≤1·5 × upper limit of normal (ULN)) is allowed for patients with Gilbert's disease
• Aspartate aminotransferase (AST) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• Alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with liver metastases
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Women of childbearing potential should have a negative urine or serum pregnancy test within 14 days of study registration. NOTE: Women are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• Women of childbearing potential and males must be willing to abstain from heterosexual activity or to use a form of effective method of contraception from the time of informed consent until 30 days after treatment discontinuation.
• As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

You cannot join if

• 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).

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

OFF regimen. A chemotherapy regimen that includes leucovorin, 5-fluorouracil and oxaliplatin, which may be used in the treatment of pancreatic cancer. NCI Drug Dictionary

ado-trastuzumab emtansine. An antibody-drug conjugate (ADC) consisting of the recombinant anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody trastuzumab conjugated to the maytansinoid DM1 via a nonreducible thioether linkage (MCC) with potential antineoplastic activity. The trastuzumab moiety of this ADC binds to HER2 on tumor cell surfaces; upon internalization, the DM1 moiety is released and binds to tubulin, thereby disrupting microtubule assembly/disassembly dynamics and inhibiting cell division and the proliferation of cancer cells that overexpress HER2. Linkage of antibody and drug through a nonreducible linker has been reported to contribute to the improved efficacy and reduced toxicity of this ADC compared to similar ADCs constructed with reducible linkers. NCI Drug Dictionary

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

nivolumab. A fully human immunoglobulin (Ig) G4 monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed death-1 (PD-1, PCD-1) with immune checkpoint inhibitory and antineoplastic activities. Upon administration, nivolumab binds to and blocks the activation of PD-1, an immunoglobulin superfamily (IgSF) transmembrane protein, by its ligands programmed cell death ligand 1 (PD-L1), which is overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on antigen-presenting cells (APCs). This results in the activation of T cells and cell-mediated immune responses against tumor cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity. NCI Drug Dictionary

Treatments listed in the registry

• Nal-IRI (Drug): chemotherapy drug
• Oxaliplatin (Drug): chemotherapy drug
• 5-FU (Drug): chemotherapy drug
• Trastuzumab (Drug): immunotherapy
• Pembrolizumab (Drug): immunotherapy
• Nivolumab (Drug): immunotherapy

Non Randomized · Single Group · masking: None

Main goals

• Cohort 1: Objective Response Rate (ORR) (up to 1 year)
• Cohort 3: Objective Response Rate (ORR) (up to 1 year)
• Cohorts 2 and 4: Incidence of Adverse Events (up to 1 year)

Other goals

• Progression Free Survival (PFS)
• Disease Control Rate (DCR)
• Progression Free Survival at 6 months
• Progression Free Survival at 12 months
• Cohorts 1 and 3: Incidence of Adverse Events
• Cohorts 2 and 4: Overall Response Rate

Planned enrollment: 52 (estimated).

• University of Wisconsin Carbone Cancer Center, Madison, Wisconsin

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT04150640
• NCI Drug Dictionary: C1181
• NCI Drug Dictionary: C1647
• NCI Drug Dictionary: C106432
• NCI Drug Dictionary: C68814

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jun 22, 2026. Public record; not medical advice.