Perioperative Toripalimab and Endostatin for Stage II Melanoma: A Phase II Trial

Inclusion Criteria:

1. Age ≥ 18 years, regardless of gender;

2. ECOG performance status: 0-1;

3. Patients with histologically or cytologically confirmed cutaneous or acral malignantmelanoma, excluding mucosal and uveal melanoma;

4. Patients with BRAF, CKIT, and NRAS gene test results;

5. Treatment-naïve patients who have not received prior anti-tumor therapy;

6. Clinical stage II (AJCC 8th edition, 2017);

7. Laboratory tests must meet the following criteria:

8. Hematology: Hemoglobin (Hb) ≥90 g/L (no transfusion within 14 days); absoluteneutrophil count (ANC) ≥1.5×10^9/L; platelet count (PLT) ≥100×10^9/L;

9. Biochemistry: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN; total bilirubin (TBIL) ≤1.5×ULN; serum creatinine (Cr) ≤1.5×ULN, and creatinine clearance >50 μmol/L;

10. Coagulation: Activated partial thromboplastin time (APTT), internationalnormalized ratio (INR), and prothrombin time (PT) ≤1.5×ULN;

11. Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%;

12. Female patients must agree to use contraception (e.g., intrauterine device [IUD],oral contraceptives, or condoms) during the study and for 6 months after studycompletion. A negative serum or urine pregnancy test within 7 days before enrollmentis required, and patients must be non-lactating. Male patients must agree to usecontraception during the study and for 6 months after study completion;

13. Patients must voluntarily participate in the study, sign the informed consent form,and demonstrate good compliance.

Exclusion Criteria:

1. History of allergic reactions to biological products;

2. Patients with prior or concurrent malignancies within 5 years (except cured basalcell carcinoma of skin or carcinoma in situ of cervix);

3. Any active autoimmune disease or history of autoimmune disorders (including but notlimited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis,nephritis; asthma requiring bronchodilators for medical intervention). Exceptionsinclude: vitiligo, psoriasis, alopecia not requiring systemic therapy,well-controlled type I diabetes, or hypothyroidism with normal thyroid function onreplacement therapy;

4. Requirement for immunosuppressive therapy using systemic or absorbable topicalcorticosteroids (equivalent to prednisone >10mg/day) within 2 weeks prior to firstdose;

5. Any history or evidence of bleeding diathesis regardless of severity; grade ≥3bleeding events per CTCAE v5.0 within 4 weeks prior to first dose; or presence ofunhealed wounds, fractures, active gastrointestinal ulcers, ulcerative colitis,tumors with active bleeding, or other conditions deemed by investigators topotentially cause gastrointestinal hemorrhage or perforation;

6. Patients with severe and/or uncontrolled comorbidities including:

7. Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥90 mmHg);

8. Unstable angina, myocardial infarction, ≥grade 2 congestive heart failure, orarrhythmias requiring treatment (including QTc ≥480ms) within 6 months prior tofirst dose;

9. Active or uncontrolled severe infections (≥grade 2 per CTCAE);

10. Clinically significant liver disease including viral hepatitis (active HBVinfection with HBV DNA >1×10³ copies/mL or >500 IU/mL; HCV infection with HCVRNA >1×10³ copies/mL or >100 IU/mL), decompensated liver disease, or chronichepatitis requiring antiviral therapy;

11. HIV-positive status;

12. Poorly controlled diabetes (fasting glucose ≥grade 2 per CTCAE);

13. Urinalysis showing proteinuria ≥++ with 24-hour urinary protein >1.0 g;

14. Administration of live vaccines within 4 weeks prior to treatment or anticipatedneed during study;

15. Other conditions deemed by investigators to potentially lead to premature studytermination, including: severe comorbidities (including psychiatric disorders)requiring concomitant therapy, significant laboratory abnormalities, orsocial/family factors that may compromise patient safety or data/sample collection.