Can a direct hit to tumors make immunotherapy work better?

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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