A Study of 2141-V11 in People With Esophageal, Gastric, or Gastroesophageal Junction Adenocarcinoma

Inclusion Criteria

• Histologically confirmed esophageal, gastric, or gastroesophageal junction adenocarcinoma

• Locally advanced unresectable or metastaticdisease at diagnosis

• On first line systemic therapy including fluoropyrimidine + anti-PD-1 therapy for advanced GEA (e.g. FOLFOX + nivolumab) for a minimum of 3 months and no more than 9 months.

  • Platinum chemotherapy included in first line regimen has been discontinued or will be discontinued ≥2 weeks prior to first planned dose of 2141-V11
  • Patients in the safety lead-in cohort must be on 5-FU

• Primary esophageal, gastric, or gastroesophageal junction tumor intact and visible at time of enrollment (within 1 month of 2141-V11 treatment initiation) on endoscopy

• Evaluable disease at time of 2141-V11 treatment initiation as defined per RECIST v1.1

• Able to undergo endoscopy

• Age 18 years or older

• ECOG performance status 0 to 1 (See Appendix I for performance status criteria)

• Adequate organ function as defined by:

  • Absolute neutrophil count ≥1000/mcL
  • Platelets ≥90,000/mcL
  • Hemoglobin ≥8 g/dL
  • Serum creatinine ≤1.5X ULN
  • Serum total bilirubin ≤1.5X ULN OR Direct bilirubin ≤ULN for participants with total bilirubin levels >1.5X ULN, except patients with Gilbert's disease (≤3X ULN)
  • AST and ALT ≤3X ULN
  • Albumin ≥3 mg/dL Abbreviations: ALT, alanine aminotransferase; AST, aminotransferase; ULN, upper limit of normal.

Exclusion Criteria

• Mismatch repair deficient (dMMR) disease by IHC or microsatellite instability (MSI-H) by next-generation sequencing

• Known HER2-positive disease (IHC 3+ or IHC 2+ and amplification via fluorescence in situ hybridization)

• Prior radiation therapy to primary esophageal, gastric, or gastroesophageal junction tumor

• Anti-PD-1 therapy in ongoing regimen has been discontinued for any reason

• Disease progression on frontline therapy

• Patients with active autoimmune disease requiring ongoing systemic steroids or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment.

• Ongoing systemic steroids or receipt of systemic steroid therapy exceeding prednisone 10 mg/day or equivalent within 7 days before first dose, except physiologic replacement or short-course premedication (e.g. as antiemetics or CT scan contrast premedication), or any other form of immunosuppressive therapy within 7 days before the first dose of trial treatment. Use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.

• Patients with active infection on parenteral antibiotics

• Patients with history of grade 3 or higher immune related adverse events to anti-PD-1 therapy may only be enrolled with the permission of the study PI.

• Prior treatment before ongoing regimen for any reason with PD-1, PD-L1, or CTLA-4 inhibitors

• Currently participating in a therapeutic study and receiving study therapy or has participated in a therapeutic study within 4 weeks of the first dose of treatment. Radiographic protocols including protocols with experimental tracers are not considered therapeutic studies and are exempt.

• Known active central nervous system metastases and/or leptomeningeal disease

• HIV, HBV, and HCV testing do not need to be performed as part of the study. For patients with known HIV, HBV, and/or HCV infection:

  • HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
  • For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

• Unwilling to give written, informed consent, unwilling to participate, or unable to comply with the protocol for the duration of the study