APX005M With Concurrent Chemoradiation for Resectable Esophageal and Gastroesophageal Junction Cancers

Open to people ages 18 years and up

1. Age ≥ 18 years of age
2. Histologically proven squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma of the esophagus or GE junction.
3. Surgically resectable (T1-3 Nx by endoscopic ultrasound). Excluded are:
4. Very early stage tumors (T1N0)
5. Cervical esophageal tumors
6. Tumors invading the tracheobronchial tree or associated with tracheoesophageal fistula
7. Any evidence of distant metastases (as determined by endoscopic ultrasound (EUS) or CT/PET)
8. Cervical, supraclavicular, or other nodal disease that is either not included in the radiation field or is not able to be resected at the time of esophagectomy
9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1
10. Adequate hematological, renal, and hepatic parameters defined as follows:
11. Absolute Neutrophil Count (ANC) ≥1.5 × 109/L in absence of growth factor support
12. Platelet count ≥150 × 109/L
13. Hemoglobin >9 g/dL
14. Serum creatinine ≤1.5 mg/dL, or calculated (using the formula of Cockcroft and Gault) or measured creatinine clearance ≥30 mL/min
15. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x upper limit of normal (ULN)
16. Total bilirubin ≤1.5x ULN
17. Women of child bearing potential (WOCBP) must have a negative serum pregnancy test within the 7 days prior to investigational product administration and a negative urine pregnancy test within the 3 days prior to the first investigational product administration, or a negative serum pregnancy test within the 3 days prior to the first investigational product administration
18. WOCBP and male subjects who are sexually active with WOCBP must agree to use 2 highly effective methods of contraception (including a physical barrier) during the study and for 30 days following the last dose of investigational product
19. Ability to understand a written informed consent document, and the willingness to sign it

1. Any history of or current hematologic malignancy
2. History of a second primary cancer is allowed in the event the cancer is curatively resected and there is no evidence of recurrence/metastatic disease x 1 year. Subjects who have a history of cervical or breast carcinoma in situ, localized prostate cancer, adequately treated basal cell or squamous cell carcinoma of the skin, or superficial bladder tumors [Ta, Tis & T1] are also allowed
3. Major surgery within 4 weeks of first dose of investigational product
4. Prior or concurrent treatment with any anticancer agent for the same cancer diagnosis
5. Prior exposure to any immuno-oncology agents, including CD40/PD-1/PD-L1/CTLA-4 inhibitors (if any ambiguity, should be discussed with study principal investigator)
6. History of bone marrow transplantation
7. Uncontrolled diabetes or hypertension
8. History of autoimmune disorders with the exception of vitiligo or autoimmune thyroid disorders
9. Chronic steroid dependency (prednisone equivalent > 10 mg/day). Any steroid use should be discontinued at least 2 weeks prior to initiation of study treatment.
10. . History of sensitivity or allergy to monoclonal antibodies (mAbs) or immunoglobulin G (IgG)
11. . History of severe hypersensitivity reaction to Cremophor EL.
12. . Pre-existing > grade 2 peripheral sensory neuropathy.
13. . Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months before first dose
14. . History of any arterial thromboembolic event within 3 months prior to first dose of investigational product
15. . Active coagulopathy
16. . Active known clinically serious infections (> Grade 2 National Cancer Institute (NCI)-CTCAE version 4.03)
17. . Known human immunodeficiency virus (HIV) infection
18. . Subjects of reproductive potential who do not use effective methods of birth control
19. . Pregnant or actively breastfeeding women
20. . Any clinically significant psychiatric, social, or medical condition that, in the opinion of the Investigator, could increase subject's risk, interfere with protocol adherence, or affect a subject's ability to give informed consent.