Trilaciclib Combined With Concurrent Chemoradiotherapy and Immunotherapy in the Treatment of Esophageal Cancer

Inclusion Criteria:

• Patients voluntarily participated in this study, signed the informed consent form,and had good compliance;

• Age ≥ 18 years old, male or female;

• Patients with histologically confirmed locally advanced esophageal squamous cellcarcinoma at stage II-IV that is unresectable, or where surgery is contraindicatedor refused (according to the AJCC 8th edition, the clinical stage before treatmentwas: cT1N2-3M0, cT2-4bN0-3M0, M1 limited to non-regional lymph node metastasis,excluding distant organ metastasis);

• The presence of at least one measurable lesion according to the response evaluationcriteria in solid Tumors (RECIST1.1);

• Have not received any systemic anti-tumor therapy (including but not limited tosystemic chemotherapy, radiotherapy, molecular targeted drug therapy, immunotherapy,biological therapy, local therapy, and other investigational therapeutic drugs);

• ECOG: 0-1 ;

• Expected survival time ≥ 6 months;

• Vital organ function meets the following requirements (no blood components and cellgrowth factors are allowed for 2 weeks before the start of screening examination) ：Absolute neutrophil count (ANC) ≥1.5×109/L；Platelet count ≥100×109/L；Hemoglobin ≥100 g/L in women or 110g/L in men；Serum albumin ≥2.8g/dL；Total bilirubin ≤1.5 × ULNand ALT, AST, and/or AKP≤2.5 × ULN

, serum creatinine 1.5 x ULN or creatinine clearance or greater or less 60 ml/min (according to Cockcroft - Gault formula);

• International standardization ratio (INR) and part activated clotting time (APTT)live enzymes acuities were 1.5 x ULN (for the use of stable doses of anticoagulantssuch as: low molecular heparin or warfarin and INR within the scope of the expectedtreatment of anticoagulants can filter);

• Women: All women of childbearing potential must have a negative serum pregnancy testat screening and must be using reliable contraception from written informed consentuntil 3 months after last dose.

Exclusion Criteria:

• History of esophageal cancer surgery;

• Previous history of fistula caused by primary tumor invasion;

• High risk of gastrointestinal bleeding, esophageal fistula, or esophagealperforation;

• Subjects with poor nutritional status, who lost more than 10% of their body weightwithin 2 months before screening, had no significant improvement after nutritionalintervention;

• major surgery or severe trauma within 4 weeks before the first dose of study drug;

• Uncontrollable pleural effusion, pericardial effusion or ascites requiring repeateddrainage; 7. Have received or are receiving any of the following：Anti-PD-1 oranti-PD-L1 antibody therapy, chemotherapy, radiotherapy, targeted therapy； receivedany study drug within 4 weeks before the first dose of the study drug； within 2weeks before first use of the drugs need to be given corticosteroid (> 10 mg dailyprednisone dose equivalent) or other immune inhibitors for treatment of the subjectssystem, except for local inflammation of the esophagus and prevent allergy andnausea, vomiting, use of corticosteroids；Have received an antitumor vaccine or alive vaccine within 4 weeks before the first dose of study drug;

• Have any active autoimmune disease or history of autoimmune disease (e.g.,interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis,myocarditis, nephritis, hyperthyroidism, hypothyroidism); Patients with vitiligo orcured asthma/allergy in the same year era who did not need any intervention afteradulthood were excluded. Patients with autoimmune-mediated hypothyroidism treatedwith stable doses of thyroid replacement hormone and patients with type I diabetestreated with stable doses of insulin were eligible.

• A history of immunodeficiency, including HIV positive, other acquired or congenitalimmunodeficiency diseases, or organ transplantation or allogeneic bone marrowtransplantation;

• Subjects with uncontrolled cardiac clinical symptoms or diseases such as： (1) heartfailure NYHA II or higher； (2) unstable angina ；(3) myocardial infarction within 1year ；(4) clinically significant supraventricular or ventricular arrhythmiasrequiring clinical intervention;

• Severe infection (CTC AE > 2) occurred within 4 weeks before the first dose of studydrug, such as severe pneumonia requiring hospitalization, bacteremia, and infectiouscomplications; Patients with active pulmonary inflammation on baseline chest imagingor signs and symptoms of infection requiring treatment with oral or intravenousantibiotics within 2 weeks before the first dose of study drug were excluded ifprophylactic antibiotics were used.

• History of interstitial lung disease, non-infectious pneumonia, pulmonary functiontest confirmed ≥ grade 3 pulmonary dysfunction;

• Patients with active pulmonary tuberculosis infection detected by medical history orCT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosisinfection more than 1 year before enrollment but without regular treatment;

• The subject has active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL),hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit ofthe analytical method);

• There were more than grade 1 abnormal sodium, potassium, and calcium laboratory testvalues within 2 weeks before enrollment, which could not be improved aftertreatment;

• Allergy to any study drug or its components;

• Prior hematopoietic stem cell or bone marrow transplantation;

• Any other malignancy diagnosed before the first use of study drug, except those witha low risk of metastasis and death (5-year survival rate > 90%), such as adequatelytreated basal cell or squamous cell skin cancer or cervical carcinoma in situ;

• Judging by the researchers, the participants have other factors that could lead tothe forced midway termination of studies..