Toripalimab in the Neoadjuvant Treatment of BRAF V600 Wild Type Melanoma (FU-Name-T001)

This is an interventional treatment trial for Melanoma Stage IIIB-IV Read More

Inclusion Criteria:

• Patients who can undergo surgery after discussion by three surgeons with a deputy senior title or higher
• Patients with stage III or oligometastasis stage IV malignant melanoma confirmed by histopathology or cytology. Stage III is defined as at least one clinically accessible lymph node metastasis; oligometastasis stage IV is defined as less than 4 metastases and the site of metastasis excludes bone metastases, brain metastases, or other metastases that cannot be completely surgically treated.
• BRAF V600 wild type
• Age ≥ 18 years old
• ECOG score is 0-1, with an estimated overall survival of more than 1 year

• The function of main organs and bone marrow is basically normal:

  1. Blood routine: WBC ≥ 3500 / mm3 (3.5 * 109 / L); Neutrophil count (ANC) ≥ 180 / mm3 (1.8 * 109 / L); Platelet count ≥ 125000 / mm3 (125 * 109 / L); Hemoglobin: male ≥ 13g / dl (130g / L); female ≥ 11.5g/dl (115g / L);
  2. Blood biochemistry: Total bilirubin ≤ 1.5 * ULN (total bilirubin of Gilbert syndrome <3.0mg / dL); Aspartate aminotransferase (AST / SGOT), alanine aminotransferase (ALT / SGPT) and alkaline phosphatase ≤ 2.5 * ULN; Creatinine ≤1.5 * normal upper limit (ULN);
  3. Coagulation function: The international standard ratio (INR) is less than 1.5 (or the INR value is 2-3 when patients take farwarin stably for a long time), and prothrombin time (PT) is less than 1.5 * ULN;
  4. Lung function test: Lung diffusion (DLCO) ≥ 70% predicted OR; DLCO <70% but ≥ 55%, and the maximum oxygen uptake (VO2 max) ≥ 10L / min / kg (by cardiopulmonary assessment) or 6 minutes walking test ≥ 500 meters; Patients with DLCO <55% were not included in this study; Pulse oximetry during rest and walking ≥ 92%;
  5. Heart function test: Baseline ECG showed no prolonged PR interval or atrioventricular block;
• Women should agree to use contraceptive measures (such as intrauterine device (IUD), contraceptive or condom) during the study and within 6 months after the end of the study; women should be negative in serum or urine pregnancy test within 7 days before the study and must be non lactating; men should agree to use contraceptive measures during the study and within 6 months after the end of the study.
• Patients voluntarily joined the study, signed informed consent, and had good compliance and were able to be followed up by the trial staff.

Exclusion Criteria:

• A previous history of activity or history of any autoimmune disease (including any history of inflammatory bowel disease), or a history of syndrome requiring treatment with systemic steroids or immunosuppressive drugs (except vitiligo patients);
• Use vaccines against infectious diseases (such as influenza, varicella, etc.) within 4 weeks (28 days) after the start of the study treatment;
• Active systemic infection requiring treatment, positive detection of hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA);
• A known positive medical history or positive test result for human immunodeficiency virus or acquired immunodeficiency syndrome (AIDS);
• Patients with any serious and / or uncontrollable diseases, such as unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, serious uncontrollable arrhythmia; patients with poor blood pressure control (systolic pressure > 140 mmHg, diastolic pressure > 90 mmHg); active or uncontrollable serious infection; liver diseases such as cirrhosis , decompensated liver disease, chronic active hepatitis; poor control of diabetes mellitus (FBG > 10mmol / L); routine urine test indicated that urine protein was ≥ + +, and confirmed that 24-hour urine protein quantity was > 1.0g;
• A history of psychotropic substance abuse who are unable to quit or have a mental disorder;
• Have been previously exposed to any anti-tumor treatment, including but not limited to chemotherapy, radiotherapy, immunotherapy (such as anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA-4 antibody or any other antibody targeting T-cell co regulatory pathway), etc.; are currently using tumor related treatment or online anti-cancer drugs; are currently using anticoagulants; have received large-scale surgical treatment in the past 3 weeks;
• Previously had malignant tumors and did not achieve complete remission at least 2 years before the start of the study without other treatments (except skin basal cell carcinoma or cervical carcinoma in situ)；
• A history of previous interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease, or chest CT scans found any evidence of active pneumonia within 4 weeks before the first study medication;
• Immunosuppressive drugs were used within 2 weeks before the first study drug treatment, excluding local glucocorticoids or prednisone with systemic glucocorticoids no more than 10 mg / day or other glucocorticoids of equivalent dose;
• Pregnant or lactating women;
• Prisoners who have been illegally imprisoned or detained for non-mental or physical (such as infectious) diseases;
• Patients with a bleeding tendency (such as active peptic ulcer) or treated with anticoagulants or vitamin K antagonists such as warfarin, heparin or its analogs;
• A history of allergy to the ingredients of the study drug;
• According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of patients or affect patients to complete the study.