Immunotherapy With CCRT Followed by Surgery for Locally Advanced ESCC Patients

Exclusion Criteria

• •1. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-¬CTLA-4, anti-PD-1, anti-PD-L1 and anti-¬TIGIT therapeutic antibodies
• •2. Prior radiotherapy to head and neck, chest, or abdomen
• •3. Prior chemotherapy
• •4. Histology consistent with adenocarcinoma, small cell carcinoma or mixed carcinoma of esophagus or gastroesophageal junction.
• •5. Synchronously or metachronously diagnosed squamous cell carcinoma of aerodigestive way, other than esophageal cancer
• •6. History of malignancy other than esophageal cancer within 2 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
• •a. Patients who received endoscopic mucosal resection or dissection for superficial mucosal cancers other than ESCC within 2 years prior to screening are eligible for the study.
• •7. Prior organ transplantation including allogenic stem-cell transplantation
• •8. Current use of immunosuppressive medication, EXCEPT for the following:
• •1. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection)
• •2. systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent
• •3. steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).
• •9. Treatment with therapeutic oral or intravenous antibiotics within 2 weeks prior to registration
• •a. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• •10. Active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid diseases not requiring immunosuppressive treatment and on stable regimen are eligible.
• •11. Severe, active comorbidities which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the protocol, or limit compliance with study requirements, defined as follows:
• •1. Severe infection within 4 weeks prior to registration, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia. Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to registration. Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• •2. Transmural myocardial infarction \< 6 months prior to registration
• •3. Unstable angina or congestive heart failure requiring hospitalization \< 6 months prior to registration
• •4. Life-threatening uncontrolled clinically significant cardiac arrhythmias
• •5. Cerebral vascular accident/stroke (\< 6 months prior to enrollment)
• •6. Congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
• •7. Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
• •8. Chronic obstructive pulmonary disease exacerbation or other respiratory illness including pulmonary fibrosis requiring hospitalization or precluding study therapy at the time of registration
• •9. Uncontrolled psychiatric disorder including recent (within the past year) or active suicidal ideation or behavior
• •10. Laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results
• •11. Immune colitis, inflammatory bowel disease, immune pneumonitis
• •12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening CT scan
• •13. Active tuberculosis
• •14. Uncontrolled or symptomatic hypercalcemia (corrected calcium \> ULN)
• •15. Known history of testing positive for HIV or known acquired immunodeficiency syndrome."
• •16. Positive Epstein-Barr virus (EBV) viral capsid antigen IgM test at screening
• •a. An EBV polymerase chain reaction (PCR) test should be performed as clinically indicated to screen for active infection or suspected chronic active infection. Patients with a positive EBV PCR test are excluded.
• •17. Vaccination with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment is prohibited except for administration of inactivated vaccines
• •18. History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• •19. Known prior severe hypersensitivity to investigational product, Chinese hamster ovary cell products or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v5.0 Grade ≥ 3)
• •20. Concurrent participation in another interventional clinical trial
• •21. Pregnant or breast-feeding women
• •22. Women of childbearing potential and male participants who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the radiation treatment involved in this study may be significantly teratogenic