| Eligibility |
Inclusion Criteria:
1. Sign written informed consent before implementing any trial-related procedures; 2. Male
or female, age =18 years old; 3. Patients with histologically confirmed esophageal squamous
cell carcinoma, diagnosed as cT4a, T4b, NXM0 according to the 8th edition of AJCC TNM
staging, and assessed as initially unresectable by the surgeon; 4. Have not received any
systemic treatment for the current disease in the past, including surgery, anti-tumor
radiotherapy, chemotherapy/immunotherapy, etc.; 5. Patients who agree to undergo radical
surgical treatment and are judged by the surgeon to have no contraindications to surgery 6.
ECOG score 0-1 points; 7. Expected survival time >6 months; 8. With sufficient organ
function, subjects must meet the following laboratory indicators:
1. Absolute neutrophil count (ANC) =1.5x109/L without using granulocyte
colony-stimulating factor in the past 14 days;
2. Without blood transfusion in the past 14 days, platelets =100×109/L;
3. Hemoglobin >9g/dL without blood transfusion or erythropoietin use in the past 14 days;
4. Total bilirubin =1.5×upper limit of normal (ULN);
5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are within
=2.5×ULN
6. Serum creatinine =1.5×ULN and creatinine clearance (calculated using the
Cockcroft-Gault formula) =60 ml/min;
7. Good coagulation function, defined as international normalized ratio (INR) or
prothrombin time (PT) = 1.5 times ULN;
8. Euthyroid, defined as thyroid stimulating hormone (TSH) within the normal range. If
baseline TSH is outside the normal range, subjects can also be enrolled if total T3
(or FT3) and FT4 are within the normal range;
9. Myocardial enzyme spectrum is within the normal range (if the researcher
comprehensively judges that simple laboratory abnormalities without clinical
significance are also allowed to be included); 9. Female subjects of childbearing
potential should receive a urine or serum pregnancy test with a negative result within
3 days before receiving the first dose of study drug (Day 1 of Cycle 1). If a urine
pregnancy test result cannot be confirmed as negative, a blood pregnancy test is
required. Women of non-reproductive age were defined as at least 1 year
postmenopausal, or had undergone surgical sterilization or hysterectomy; 10. If there
is a risk of pregnancy, all subjects (regardless of male or female) need to use low
annual failure rate during the entire treatment period until 120 days after the last
dose of study drug (or 180 days after the last dose of chemotherapy drug).
Contraceptive measures at 1%.
Exclusion Criteria:
1. Other malignant diseases diagnosed within 5 years before the first dose (excluding
radical basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin,
and/or carcinoma in situ that has been radically resected);
2. Endoscopically known signs of active bleeding in the lesion;
3. Currently participating in interventional clinical research treatment, or have
received other research drugs or used research equipment within 4 weeks before the
first dose;
4. Have previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2
drugs or another type of stimulating or synergistic inhibition of T cell receptors
(including but not limited to CTLA-4, OX-40, CD137 etc.) drugs;
5. Have received systemic systemic treatment with Chinese patent medicines with
anti-tumor indications or drugs with immunomodulatory effects (including thymosin,
interferon, interleukin, except for local use to control pleural effusion) within 2
weeks before the first dose;
6. Active autoimmune disease that requires systemic treatment (such as the use of
disease-modifying drugs, glucocorticoids, or immunosuppressants) has occurred within 2
years before the first dose. Replacement therapies (such as thyroxine, insulin, or
physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not
considered systemic treatments;
7. Are receiving systemic glucocorticoid treatment (excluding nasal spray, inhaled or
other local glucocorticoids) or any other form of immunosuppressive therapy within 7
days before the first dose of the study; Note: Physiological doses of glucocorticoids
(=10 mg/day of prednisone or equivalent) are allowed;
8. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic
hematopoietic stem cell transplantation;
9. People who are known to be allergic to the drugs used in this study;
10. Those with multiple factors that affect capecitabine (such as inability to swallow,
intestinal obstruction, etc.);
11. Have not fully recovered from toxicity and/or complications caused by any intervention
before initiating treatment (i.e., =Grade 1 or reaching baseline, excluding fatigue or
alopecia);
12. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody
positive);
13. Untreated active hepatitis B (defined as HBsAg positivity and a detected HBV-DNA copy
number greater than the upper limit of normal value in the laboratory of the research
center);
Note: Hepatitis B subjects who meet the following criteria can also be enrolled:
1. The HBV viral load before the first dose is <2500 copies/ml (500 IU/ml), and the
subject should receive anti-HBV treatment during the entire study chemotherapy drug
treatment period to avoid viral reactivation.
2. Subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-) do not need
to receive prophylactic anti-HBV treatment, but need to be closely monitored for viral
reactivation 14. Subjects with active HCV infection (HCV antibody positive and HCV-RNA
level higher than the lower limit of detection); 15. Get live vaccine within 30 days
before the first dose (cycle 1, day 1); NOTE: Injectable inactivated virus vaccine for
seasonal influenza is allowed within 30 days before the first dose; however,
intranasal live attenuated influenza vaccine is not allowed 16. Pregnant or lactating
women; 17. The presence of any serious or uncontrollable systemic disease, such as:
1) The resting electrocardiogram has major abnormalities in rhythm, conduction or
morphology that are difficult to control with severe symptoms, such as complete left bundle
branch block, second degree or higher heart block, ventricular arrhythmia or atrial
fibrillation; 2) Unstable angina, congestive heart failure, New York Heart Association
(NYHA) chronic heart failure grade = 2; 3) Any arterial thrombosis, embolism or ischemia
occurred within 6 months before selected treatment, such as myocardial infarction, unstable
angina, cerebrovascular accident or transient cerebral ischemic attack; 4) Unsatisfactory
blood pressure control (systolic blood pressure >140 mmHg, diastolic blood pressure >90
mmHg); 5) There is a history of non-infectious pneumonia requiring glucocorticoid treatment
within 1 year before the first dose, or there is currently clinically active interstitial
lung disease; 6) Active pulmonary tuberculosis; 7) There is an active or uncontrolled
infection that requires systemic treatment; 8) Clinically active diverticulitis, abdominal
abscess, gastrointestinal obstruction exists; 9) Liver diseases such as cirrhosis,
decompensated liver disease, acute or chronic active hepatitis; 10) Poorly controlled
diabetes (fasting blood glucose (FBG) >10mmol/L); 11) Those whose urine routine shows urine
protein =++, and the 24-hour urine protein quantification is confirmed to be >1.0 g; 12)
Patients with mental disorders and unable to cooperate with treatment; 18. Evidence of
medical history or disease, abnormal treatment or laboratory test values that may interfere
with the trial results, prevent the subject from fully participating in the study, or other
circumstances that the researcher believes are not suitable for enrollment. The researcher
believes that there are other potential risks and are not suitable for participation this
research.
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