Overview

Participants will receive study treatment with agenT-797, botensilimab, balstilimab, ramucirumab, and paclitaxel. When participants start each agent will depend on how their disease is affecting them.

Eligibility

Inclusion Criteria:

• Metastatic or advanced unresectable adenocarcinoma of esophageal, gastric, or gastroesophageal junction
• Disease progression on one prior line of therapy for metastatic disease
• Patients must have histologically or cytologically confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma
• Patients must have measurable or evaluable disease as defined by RECIST v1.1 criteria. Patients with evaluable disease must be eligible to begin with an induction cycle
• Age 18 years or older
• ECOG performance status 0 to 1
• Adequate organ function as defined in Table 2

        Table 2. Organ function requirements for eligibility Hematological Absolute neutrophil
        count: ≥1000/mcL Platelets: ≥90,000/mcL Hemoglobin: ≥8 g/dL Renal Serum creatinine: ≤1.5X
        ULN Hepatic Serum total bilirubin: ≤1.5X ULN OR Direct bilirubin ≤ULN for subjects with
        total bilirubin levels >1.5X ULN, except patients with Gilbert's disease (≤3X ULN) AST and
        ALT: ≤2.5X ULN Albumin: ≥3 mg/dL
        Exclusion Criteria:
          -  Received prior therapy with ramucirumab at any time
          -  Received paclitaxel or docetaxel-based therapy within 6 month of study enrollment
          -  Had a prior grade >3 immune related adverse event due to anti-PD-1, anti-PD-L1,
             anti-PD-L2, or anti-CTLA4 therapy at any time
          -  Diagnosis of immunodeficiency or receipt of systemic steroid therapy or any other form
             of immunosuppressive therapy within 7 days before the first dose of trial treatment.
             Replacement therapy (ie physiologic corticosteroid replacement therapy for adrenal or
             pituitary insufficiency) is not considered a form of systemic immunosuppressive
             therapy and is allowed.
          -  History of gastrointestinal perforation or fistulae
          -  A known history of active Bacillus tuberculosis
          -  Known active central nervous system metastases and/or carcinomatous meningitis
          -  History of or any evidence of active, non-infectious pneumonitis
          -  Peripheral neuropathy limiting ADLs
          -  A known history of human immunodeficiency virus (HIV 1/2 antibodies)
          -  Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA
             [qualitative] is detected). Patients with HBsAg reactive on entecavir may be eligible
             after consultation with hepatologist and study team.
          -  Received a live vaccine within 30 days of planned start of study therapy
          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial
          -  Pregnant or breastfeeding or expecting to conceive or father children within the
             projected duration of the trial, starting with the prescreening or screening visit
             through 5 months after the last dose of trial treatment
          -  Unwilling to give written, informed consent, unwilling to participate, or unable to
             comply with the protocol for the duration of the study