Inclusion Criteria:

• Patients must have histologically confirmed and clinically staged T2 or higher or node positive, non-metastatic esophageal, gastroesophageal junction, or gastric adenocarcinoma.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• Patents must be deemed a surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform the appropriate surgical procedure based on patient's primary tumor site.
• Patients must have normal organ and bone marrow function, as defined below, less than or equal to 14 days prior to the initiation of study therapy:
  • Absolute neutrophil count (ANC) ≥ 1,500/microliter
  • Platelets ≥100,000/microliter
  • Total bilirubin ≤ the institutional upper limit of normal (ULN).
  • AST and ALT ≤ 2.5 times the institutional ULN
  • Serum creatinine ≤ 1.5 times the institutional ULN
  • Hemoglobin ≥ 9 g/dL

Exclusion Criteria

• Has received prior chemotherapy, radiation therapy, or immunotherapy (anti-programmed cell death protein-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) for the current malignancy.
• Per the investigator, has contraindications to receiving chemotherapy with FLOT.
• Per the sub-investigator (gastroenterologist) responsible for intra-tumoral injections or the investigator, patient has contraindications to repeated upper endoscopy for intra-tumoral injections. These could include medical conditions that would, per the judgment of the sub-investigator or investigator, inappropriately increase the risk of upper endoscopy.
• Conditions in which anticoagulant therapies cannot be safely stopped in the periprocedural period or patients on warfarin with a target international normalized ratio (INR) ≥ 2.5 that cannot be temporarily reversed to INR ≤ 1.7.
• Active significant herpetic infections or prior complications of Herpes simplex virus-1 (HSV-1) infection (e.g., herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or intravenous [IV]) antivirals with known antiherpetic activity (e.g., acyclovir). Note: Patients with sporadic cold sores may be enrolled as long as no active cold sores are present at the time of first dose of study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed, however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Available COVID-19 vaccines do not contain live virus and are allowed.
• Has a condition requiring systemic treatment with corticosteroids (>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of first study treatment administration.
  • Inhaled or topical steroids and adrenal replacement doses ≤ 10mg/day of prednisone equivalents are permitted.
• Prior organ transplantation including allogeneic stem-cell transplantation.
• Has a previous or concurrent malignancy. Exceptions include:
  • Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ OR
  • Prior malignancy has been completely excised or removed and patient has been continuously disease free for > 5-years
• Has a positive test result for hepatitis B virus surface antigen (HBsAg) or

  hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection with hepatitis B or hepatitis C. Testing will be performed as part of screening on the study.

  • Patients with a known history of hepatitis B or hepatitis C that have been effectively treated (with negative HBsAg and HCV RNA) will be eligible for enrollment on this criterion.
• Has a known history of human immunodeficiency virus (HIV) with detectable viral

  load. HIV testing will not be performed as part of screening for the study.

  • Patients with known HIV infection with an undetectable viral load and who are on a stable highly active antiviral regimen per the investigator's assessment will eligible to enroll.
• Has a psychiatric illness, substance use, or other social conditions that, in the

  judgment of the investigator, would limit compliance with study requirements.