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

Prior treatment

• Prior radiation therapy to primary esophageal, gastric, or gastroesophageal junction tumor
• Anti-PD-1 therapy in ongoing regimen has been discontinued for any reason
• 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.
• 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.
• 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.

Other illness

• 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)
• Disease progression on frontline therapy
• 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.
• Known active central nervous system metastases and/or leptomeningeal disease

Other

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

• 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.