Stomach Cancer Clinical Trials

• Patients must have a pathologically confirmed diagnosis of adenocarcinoma of the esophagus, gastroesophageal junction, stomach. Squamous cell tumors are excluded. Patients with locally tested HER2 positive tumors (HER2+) tumors are excluded.

• Participants must have disease that can be evaluated radiographically. This includes disease that may be measurable or non-measurable as per RECIST version 1.1.

• Patients may not have received prior therapy for Stage IV disease. Patients may have received prior adjuvant therapy if more than 6 months have elapsed between the end of adjuvant therapy and registration.

• Age ≥18 years old. Because there is no dosing or adverse event data for ivonescimab with FOLFOX in participants \<18 years of age, children are excluded from this study.

• ECOG Performance status of 0-2

• Participants must meet the following organ and marrow function as defined below:

‣ absolute neutrophil count ≥1,500/mcL

⁃ hemoglobin \> 9.0 g/dL

⁃ platelets ≥100,000/mcL

⁃ total bilirubin ≤ 1.5x institutional upper limit of normal (ULN). For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN

⁃ AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN. For patients with liver metastases, AST and ALT ≤ 5 × ULN

⁃ Creatinine ≤ institutional ULN OR glomerular filtration rate (GFR) ≥50 mL/min.

⁃ Urine protein \< 2+ or 24-hour protein quantification \< 1.0 grams.

⁃ Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy) This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose.

• For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

• Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

• Participants with brain metastases (active brain metastases) or leptomeningeal disease are not eligible. Patients with treated brain metastases who are off systemic steroids \> 2 weeks and have documented radiographic stability over 4 weeks since initial brain metastasis diagnosis may be considered in discussion with the overall principal investigator.

• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

• The effects of ivonescimab on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Contraception should continue for 9 months from the last dose of any study medication.

• Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 9 months after completion of ivonescimab administration.

• Ability to understand and the willingness to sign a written informed consent document.