Camrelizumab in Combination With Apatinib Mesylate Plus Short-course Chemotherapy for Advanced ESCC

Inclusion Criteria:

1. Age 18-75, male or female;

2. Esophageal squamous cell carcinoma that is histologically or cytologicallyconfirmed as unresectable locally advanced/recurrent (unable to receive radicaltreatment such as radical chemoradiotherapy or radical radiotherapy) or distantmetastasis;

3. No previous systematic antitumor therapy. For patients who receivedneoadjuvant/adjuvant and radical concurrent chemoradiotherapy, the time fromthe last chemotherapy to recurrence or progression more than 6 months can bescreened;

4. According to the efficacy evaluation criteria for solid tumors (RECIST 1.1),there should be at least one measurable lesion (esophageal and other cavitystructures cannot be used as measurable lesions), and the measurable lesionsshould not have received local treatment such as radiotherapy (lesions locatedwithin the previous radiotherapy area can also be selected as target lesions ifit is confirmed to progress);

5. Agree to provide tissue samples for biomarker (such as PD-L1) analysis.Recently obtained tissues are preferred. Patients who cannot provide recentlyobtained tissues can provide 5-8 paraffin sections of 3-5 μm thickness forarchival storage;

6. ECOG PS: 0 ~ 1;

7. Swallowing pills normally;

8. Expected survival ≥12 weeks;

9. The functions of vital organs meet the following requirements (no drugs withblood components and cell growth factors are allowed to be used within 14 daysbefore the first use of the study drug);

10. Absolute count of neutrophils (ANC) ≥1.5×109/L

11. Platelet ≥90×109/L;

12. Hemoglobin ≥90g/L;

13. Serum albumin ≥28g/L;

14. Total bilirubin ≤1.5 × ULN, ALT, AST, and/or AKP≤2.5 × ULN; If liver metastasisis present, ALT and/or AST≤5 × ULN; If there is liver metastasis or bonemetastasis AKP≤5 × ULN;

15. Serum creatinine ≤1.5 × ULN or creatinine clearance > 60 mL/min (Cockcroft-Gault);

16. Activated partial thromboplastin time (APTT) and International Normalized ratio (INR) ≤1.5 × ULN (for stable dose anticoagulant therapy such as low molecularweight heparin or warfarin and INR within the expected treatment range ofanticoagulants can be screened)

10. Fertile female subjects and male subjects whose partners are women ofchildbearing age, A medically approved contraceptive (such as an intrauterinedevice, contraceptive or condom) is required during the study treatment periodand at least 2 months after the last use of carrilizumab/Apatinib mesylate andat least 6 months after the last use of chemotherapy;

11. The subjects voluntarily joined the study, signed the informed consent, hadgood compliance, and cooperated with follow-up.

Exclusion Criteria:

1. BMI < 18.5 kg/m2 or weight loss ≥10% within 2 months prior to screening (whilethe effect of large amounts of abdominal and thoracic fluids on body weightshould be considered);

2. Active hemoptysis occurred within 3 weeks before the first administration ofthe study drug, or tumor hemorrhage occurred within 2 weeks before the firstadministration of the study intervention;

3. Patients with tumors assessed by the investigator to have invaded adjacentorgans of the esophageal lesion (such as the aorta or respiratory tract) andhad a high risk of bleeding or fistula during the study;

4. Previous history of gastrointestinal perforation and/or fistula or recent (within 3 months before randomization) history of intestinal obstruction orimaging and clinical symptoms suggestive of intestinal obstruction;

5. Subjects who have had esophageal stents implanted or are evaluated for needingesophageal stents implanted;

6. Patients with clinical symptoms of pleural effusion, pericardial effusion orascites who need puncture or drainage or who have received drainage fortreatment within 1 month before randomization;

7. Have high blood pressure that is not well controlled by antihypertensivemedications (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90mmHg)

8. A history of allergies to monoclonal antibodies, any component of Camrelizumab,Apatinib mesylate and its excipients, paclitaxel, albumin paclitaxel andcisplatin;

9. Received any of the following medical treatment:

10. Received any investigational drug within 4 weeks prior to initial use of theinvestigational drug;

11. Enrolling in another clinical study at the same time, unless it is anobservational (non-interventional) clinical study or an interventional clinicalstudy follow-up;

12. Receiving the last dose of anticancer therapy (including radiotherapy, etc.)within 4 weeks or less before the first use of the study drug;

13. Subjects who required systemic treatment with corticosteroids (> 10 mg dailyequivalent of prednisone) or other immunosuppressant within 2 weeks prior toinitial use of the study drug, except for corticosteroids for local esophagealinflammation and prevention of allergy, nausea, and vomiting. In the absence ofactive autoimmune disease, inhaled or topical steroid and adrenocorticalhormone replacement at doses > 10mg/ day of prednisone efficacy dose arepermitted;

14. Those who have received anti-tumor vaccine or have received live vaccine within 4 weeks prior to the first administration of the study drug;

15. Major surgery or severe trauma within 4 weeks prior to initial use of the studydrug;

10. The toxicity of previous antitumor therapy has not recovered to ≤CTCAE Grade 1 (except hair loss) or the level specified by inclusion/exclusion criteria;

11. Patients with central nervous system metastasis;

12. History of active autoimmune diseases, autoimmune diseases (such asinterstitial pneumonia, colitis, hepatitis, pituitaries, vasculitis, nephritis,hyperthyroidism, hypothyroidism, including but not limited to these diseases orsyndromes); Except for patients with vitiligo or asthma/allergies fromchildhood that have recovered and require no intervention as adults; Autoimmunemediated hypothyroidism treated with a steady dose of thyroid replacementhormone; Type 1 diabetes using a steady dose of insulin;

13. A history of immunodeficiency, including HIV positive, or other acquired,congenital immunodeficiency diseases, or a history of organ transplantation andallogeneic bone marrow transplantation;

14. Subjects have poorly controlled cardiovascular clinical symptoms or diseases,including but not limited to: (1) NYHA Grade II or higher heart failure, (2)unstable angina pectoris, (3) previous myocardial infarction within 1 year, (4)clinically significant supraventricular or ventricular arrhythmias that are notwell controlled without clinical intervention or after clinical intervention;

15. Severe infections (CTCAE > Grade 2), such as severe pneumonia, bacteremia, andinfection complications requiring hospitalization, occurred within 4 weeksprior to the first use of the study drug; Baseline chest imaging indicatedactive pulmonary inflammation, signs and symptoms of infection within 2 weeksprior to initial use of the study drug, or the need for oral or intravenousantibiotic treatment, except for the use of prophylactic antibiotics;

16. History of interstitial lung disease (except radiation pneumonia withouthormone therapy) and non-infectious pneumonia;

17. Patients with active tuberculosis infection identified by medical history or CTexamination, or with a history of active tuberculosis infection within 1 yearprior to enrollment, or with a history of active tuberculosis infection morethan 1 year ago but without formal treatment;

18. Subjects had active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL),hepatitis C (HCV antibody positive and HCV-RNA above the assay limit);

19. Bleeding symptoms of significant clinical significance or definite bleedingtendency, such as digestive tract bleeding, hemorrhagic ulcer or vasculitis,have occurred within 3 months before randomization. If stool occult blood ispositive in baseline period, review can be conducted; if it is still positiveafter review, combined with clinical judgment, gastroscopy should be performedif necessary;

20. Arteriovenous thrombosis events occurring within 6 months prior torandomization, such as cerebrovascular accident (including temporary ischemicattack, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis andpulmonary embolism, etc. Superficial vein thrombosis could be included afterbeing determined by the researchers;

21. Known hereditary or acquired bleeding and thrombotic tendencies (e.g.haemophiliacs, coagulation disorders, thrombocytopenia, etc.);

22. With active ulcers, unhealed wounds or with fractures;

23. Urine routine indicated urinary protein ≥ ++ and confirmed 24-hour urinaryprotein volume &gt; 1.0g;

24. Subjects were still using a strong CYP3A4 inducer within 2 weeks beforerandomization, or were still using a strong CYP3A4 inhibitor within 1 weekbefore randomization;

25. Any other malignancies diagnosed within five years prior to the first use ofthe study drug, other than those with a low risk of metastasis and death (5-year survival > 90%), such as basal or squamous cell skin cancer orcarcinoma in situ of the cervix after adequate treatment;

26. Pregnant or lactating women;

27. In the investigator's judgment, the subjects had other factors that might haveled to their being forced to terminate the study, such as other serious medicalconditions (including mental illness) requiring concomitant treatment, seriousabnormalities in laboratory test values, or family or social factors that mighthave affected the subjects' safety or the circumstances in which the study datawere collected.