Apatinib Combined With Camrelizumab in Treating Participants With Advanced Chordoma

Inclusion Criteria:

1\. Age ≥ 16 years old, male or female; 2. The physical status score of the Eastern Cancer Collaboration Group (ECOG) was 0-1; 3. Expected survival ≥3 months; 4. Patients with advanced chordoma confirmed by histopathology; 5. Imaging was available to evaluate the lesions. According to the evaluation criteria for solid tumor efficacy (RECIST 1.1, see Annex 2), there was at least one single-diameter measurable lesion, whose longest diameter was measured by spiral CT ≥ 10 mm; 6. All acute toxicities resulting from prior antitumor therapy were resolved to grade 0-1 (according to NCI CTCAE version 5.03) or to the level specified in the enrollment/exclusion criteria prior to enrollment (except for toxicities such as alopecia that the investigator determined did not pose a safety risk to the subject); If subjects undergo major surgery, they must have fully recovered from complications before starting treatment; 7. If the major organs function normally, the following criteria are met:

1. The standard of blood routine examination should be met (no blood transfusion and blood products within 14 days, no G-CSF and other hematopoietic stimulating factors are used to correct) :

   1. Hemoglobin (Hb) ≥ 80 g/L;
   2. Neutrophil count (ANC) ≥ 1.5×109/L;
   3. Platelet count (PLT) ≥ 80×109/L;
2. Biochemical examination shall meet the following standards:

   1. Total bilirubin (TBIL) \< 1.5 ULN;
   2. ALT and AST \< 2.5ULN, and \< 5ULN in patients with liver metastasis; Alkaline phosphatase \< 5ULN;
   3. Serum Cr ≤ ULN or endogenous creatinine clearance \> 45 ml/min. 8. Women of childbearing age must have used reliable contraception or had a pregnancy test (serum or urine) within 7 days prior to enrol, with a negative result, and be willing to use an appropriate method of contraception during the trial period and 60 days after the last dose of the test drug. For men, consent to use appropriate methods of contraception or surgical sterilization during the trial period and for 120 days after the last dose of the trial drug; 9. The subjects voluntarily joined the study and signed the informed consent, with good compliance and follow-up.

Exclusion Criteria:

1. Except for those subjects whose toxicity had not recovered from previous antitumor therapy (concurrent chemoradiotherapy, surgical treatment) (alopecia, alkaline phosphatase, glutamine detranspeptase (GGT)) or who could be enrolled after discussion with the investigator and sponsor
2. Use of immunosuppressive drugs within 14 days prior to first use of carrilizumab, excluding nasal and inhaled corticosteroids or systemic steroid hormones at physiological doses (i.e., no more than 10 mg/ day of prednisolone or other corticosteroids at pharmacologically equivalent doses);
3. Previous treatment with anti-PD-1, anti-PD-L1, anti-VEGFR antibodies or anti-PD-L2 drugs or drugs that target another stimulus or synergistically inhibit T cell receptors (e.g., CTLA-4, OX-40, CD137);
4. Uncontrolled hypertension (systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg, despite systematic medication);
5. Severe cardiovascular disease: Grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias (including QTc interval ≥450 ms for men and ≥470 ms for women); Grade Ⅲ to Ⅳ cardiac insufficiency (according to the New York Heart Society NYHA classification, see Annex 3), or left ventricular ejection fraction (LVEF) \< 50% indicated by cardiac color ultrasound;
6. Patients with any active autoimmune disease or history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism) are not included;
7. The subjects were treated with bronchodilators and other systemic treatments, but their asthma control was unsatisfactory and they could not be included (those whose asthma had been completely relieved in childhood could be included without any intervention after adulthood).
8. Urine routine suggests urinary protein ≥ ++, or confirms 24-hour urinary protein volume ≥1.0g;
9. Abnormal coagulation function (INR \>1.5 ULN or prothrombin time (PT) \> ULN+4 seconds or APTT \>1.5 ULN), have a tendency to bleed or are receiving thrombolytic or anticoagulant therapy; Note: Under the premise of INR ≤ 1.5, the use of low dose heparin (adult daily dose of 0.6 thousand to 12 thousand U) or low dose aspirin (daily dose of 100 mg or less) is permitted for preventive purposes;
10. A severe infection occurring within 4 weeks prior to the first dose (e.g., requiring intravenous antibiotic, antifungal, or antiviral medication), or an unexplained fever \>38.5°C during the screening period/prior to the first dose;
11. Severe arteriovenous thrombosis events, such as cerebrovascular accidents (including temporary ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism, occurred within 12 months before enrollment;
12. Had undergone major surgery or severe traumatic injury, fracture or ulcer within 4 weeks prior to enrollment;
13. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS), active tuberculosis, active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody positive, And HCV-RNA is higher than the lower limit of detection method) or co-infected with hepatitis B and hepatitis C;
14. Patients with a clear history of allergy may have an underlying allergy or intolerance to the biologics of Apatinib and carrilizumab;
15. There are significant factors affecting the absorption of oral drugs, such as inability to swallow, chronic diarrhoea and intestinal obstruction. Or have cavity or perforation of viscera or sinus within 6 months;
16. Those who have a history of psychotropic drug abuse and cannot quit or have mental disorders;
17. Increases the risks associated with study participation or study drugs and, in the investigator's judgment, may result in other conditions for which the patient is not eligible for study enrollment.