PhII Study of Toripalimab Followed by Definitive CRT & Adjuvant Toripalimab in Locally Advanced ESCC

Prior treatment

• Previous radiotherapy of the thorax.
• Previous immune checkpoint inhibitor therapy (including agents targeting PD-1, PD-L1/PD-L2, CTLA-4, LAG-3, TIGIT).
• Previous non-infectious pneumonitis or interstitial lung disease.
• Any severe comorbidity (e.g. uncontrolled diabetes or decompensated heart failure) which in the determination of the treating physician would preclude the patient from receiving this experimental treatment regimen.

Other illness

• Locally advanced and incurable or metastatic disease is deemed incurable.
• History of another malignancy within 3 years prior to screening, except for non-melanoma skin carcinoma, low-grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the cervix, or stage I uterine cancer.
• Multiple primary esophageal cancers.
• Active autoimmune disease, solid organ transplant recipient, or prednisone dose (or a steroid equivalent) of more than 10mg daily.
• Contraindication to ICI or suspected allergy/hypersensitivity to monoclonal antibodies or any ingredients of toripalimab.
• Known allergy/hypersensitivity to carboplatin or paclitaxel.

Other

• Inability to provide informed consent due to psychological, familial, social, or other factors.
• Presence of CTCAEv6 grade ≥ 2 neuropathy.
• Pregnant or breastfeeding.

• Signed and dated written informed consent.
• Age ≥ 18 years the day of signing informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• Previously untreated, resectable, histologically confirmed stage II-IVA esophageal squamous cell carcinoma according to the 8th TNM staging system of the American Joint Committee on Cancer.
• Has provided archival or newly obtained core or excisional biopsy tissue (fine needle aspirate \[FNA\] is not adequate) of a tumor lesion for local standard of care biomarker analysis. Repeat samples may be required if adequate tissue is not provided. Note: Formalin-fixed, paraffin embedded tissue blocks are preferred to slides.
• Adequate organ and bone marrow function resulted ≤ 28 days prior to first dose of protocol-indicated treatment:
  • Absolute neutrophil count (ANC) ≥ 1500/µL.
  • Platelets ≥ 100,000/µL.
  • Hemoglobin ≥ 7.0 g/dL
  • Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (as calculated by the Cockcroft-Gault Formula or calculated/measured by an alternative established institutional standard consistently applied across participants at the site) or serum creatinine ≤ 1.5x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 times institutional ULN
  • AST (SGOT) and ALT (SGPT) ≤ 2.5 times institutional ULN.
  • Serum albumin ≥ 2.8 g/dL