Camrelizumab Plus Apatinib in Patients With High-risk Gestational Trophoblastic Neoplasia

Exclusion Criteria13

• Previous treatment with immunotherapy drugs (including antibodies targeting PD-1, PD-L1, cytotoxic T-lymphocyte-associated protein 4, T-cell receptor, chimeric antigen receptor T-cell therapy, and other immunotherapy), anti-angiogenic small-molecule tyrosine kinase inhibitors (such as pazopanib, sorafenib, or regorafenib), or anti-angiogenic monoclonal antibodies (such as bevacizumab); live vaccines injected within 4 weeks before the first dose of study drug; other clinical trials of antitumour drugs within 4 weeks before the first dose of study drug;
• Other malignancies in the past 3 years;
• Immunosuppressive drugs used within 14 days prior to the first dose of camrelizumab; any active autoimmune disease or a history of autoimmune disease;
• Uncontrollable hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, despite with the optimal drug therapy);
• Grade II or higher myocardial ischemia, myocardial infarction or poorly controlled arrhythmia (females with QTc interval ≥470 ms); grade III to IV cardiac insufficiency according to New York Heart Association (NYHA) criteria, or cardiac color Doppler ultrasound evidence of left ventricular ejection fraction <50%; myocardial infarction, NYHA grade II or above heart failure, uncontrolled angina, uncontrolled severe ventricular arrhythmia, clinically significant pericardial disease, or electrocardiogram suggesting acute ischemia or abnormal active conduction system occurring within 6 months before enrolment;
• Abnormal coagulation (international normalised ratio >1·5×ULN or prothrombin time >ULN+4 seconds or activated partial thromboplastin time >1·5×ULN), with bleeding tendency or undergoing thrombolysis or anticoagulant therapy;
• Severe infections within 4 weeks prior to the first dose of study drug (e.g., need of intravenous infusion of antibiotics, antifungal or antiviral drugs), or unexplained fever (>38·5°C) during screening or the first dose of study drug;
• With a history of psychotropic drug abuse and are unable to withdraw the psychotropic drug, or have mental disorders;
• Major surgery performed within 4 weeks before the first dose of study drug, or open wounds or fractures;
• Obvious factors affecting oral drug absorption, such as inability to swallow, chronic diarrhea and intestinal obstruction, or sinus or perforation of empty organs within 6 months;
• Routine urine test indicating urinary protein ++ or more, or confirmed urinary protein ≥1·0 g within 24 hours;
• Human immunodeficiency virus infection or known acquired immunodeficiency syndrome, active hepatitis B (HBV DNA >500 IU/mL), hepatitis C (hepatitis C antibody positive, and HCV-RNA higher than the lower limit of the analysis method) or co-infection with hepatitis B and hepatitis C;
• Other reasons as judged by the investigator.