Phase II Study of PD-1 Inhibitor Combined With Apatinib and Mitotane in the Treatment of Advanced Adrenal Cortical Carcinoma

Exclusion Criteria

• •1. A history of other malignant tumors within the past 5 years or at the same time, except cured basal cell carcinoma of the skin, carcinoma in situ of the cervix, and thyroid papillary carcinoma;
• •2. Known allergic reactions to other monoclonal antibodies, active ingredient of mitotane, active ingredient of apatinib and or any excipients;
• •3. CNS metastases with clinical symptoms such as brain edema, requiring hormonal intervention, or progression of brain metastases;
• •4. Patients who received potent CYP3A4 inhibitor treatment within one week before enrollment or a potent CYP3A4 inducer treatment within two weeks before the first use of study drug;
• •5. Patients with hypertension not well controlled by antihypertensive drug therapy alone (systolic blood pressure \> 140 mmHg, diastolic blood pressure \> 90 mmHg);
• •6. NYHA class III-IV congestive heart failure;
• •7. Occurrence of arterial/venous thrombosis events within 1 year before enrollment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), myocardial infarction, unstable angina pectoris, deep vein thrombosis, and pulmonary embolism;
• •8. QT interval \> 500 ms;
• •9. Prior systemic immunosuppressive therapy;
• •10. Prior treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies;
• •11. TKI treatment within 2 weeks before the first dose;
• •12. Participating in other interventional drug clinical trials within 4 weeks before the first dose;
• •13. Received an antineoplastic vaccine or a live vaccine within 4 weeks before the first dose of study drug;
• •14. Major surgery or major trauma within 4 weeks before the first dose of study medication;
• •15. Had a serious infection (CTCAE \> 2) within 4 weeks before the first dose of study drug, such as severe pneumonia requiring hospitalization, bacteremia, and infectious complications; The presence of active pulmonary inflammation, symptoms and signs of infection within 2 weeks before the first dose of the study drug, or the need for treatment with oral or intravenous antibiotics (excluding prophylactic antibiotics) on baseline chest imaging.
• •16. Have an active autoimmune disease, a history of autoimmune disease (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases and syndromes); Autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type 1 diabetes on stable doses of insulin; However, patients with vitiligo or childhood asthma/allergies that had been cured and did not need any intervention in adulthood were excluded.
• •17. Have a history of immunodeficiency, including being HIV positive or having other acquired or congenital immunodeficiency disorders, or having a history of organ or bone marrow transplantation;
• •18. A history of non-infectious pneumonia;
• •19. Active pulmonary tuberculosis infection detected by medical history or CT examination, or a history of active pulmonary tuberculosis infection within 1 year before enrollment or patients who had a history of active pulmonary tuberculosis infection 1 year ago but had not received formal treatment;
• •20. Subjects with active hepatitis (HBV DNA≥2000 IU/ml or 10000 copies/ml), hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit of the assay);
• •21. A known history of psychotropic drug abuse, alcohol abuse, and drug use;
• •22. Have GI bleeding symptoms and risk of bleeding;
• •23. Are pregnant or lactating;
• •24. Have medical history, disease, treatment, or laboratory abnormalities that may interfere with the results of the trial or prevent the subject from participating fully in the study, or the investigator believes that participation in the study is not in the subject's best interest.