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

Inclusion criteria

• Age ≥ 18 years, regardless of gender;
• ECOG performance status: 0-1;
• Patients with histologically or cytologically confirmed cutaneous or acral malignant melanoma, excluding mucosal and uveal melanoma;
• Patients with BRAF, CKIT, and NRAS gene test results;
• Treatment-naïve patients who have not received prior anti-tumor therapy;
• Clinical stage II (AJCC 8th edition, 2017);
• Laboratory tests must meet the following criteria:

• Hematology: Hemoglobin (Hb) ≥90 g/L (no transfusion within 14 days); absolute neutrophil count (ANC) ≥1.5×10^9/L; platelet count (PLT) ≥100×10^9/L;
• 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;
• Coagulation: Activated partial thromboplastin time (APTT), international normalized ratio (INR), and prothrombin time (PT) ≤1.5×ULN;
• Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) ≥50%;
• Female patients must agree to use contraception (e.g., intrauterine device [IUD], oral contraceptives, or condoms) during the study and for 6 months after study completion. A negative serum or urine pregnancy test within 7 days before enrollment is required, and patients must be non-lactating. Male patients must agree to use contraception during the study and for 6 months after study completion;
• Patients must voluntarily participate in the study, sign the informed consent form, and demonstrate good compliance.

Exclusion criteria

• History of allergic reactions to biological products;
• Patients with prior or concurrent malignancies within 5 years (except cured basal cell carcinoma of skin or carcinoma in situ of cervix);
• Any active autoimmune disease or history of autoimmune disorders (including but not limited to: autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis; asthma requiring bronchodilators for medical intervention). Exceptions include: vitiligo, psoriasis, alopecia not requiring systemic therapy, well-controlled type I diabetes, or hypothyroidism with normal thyroid function on replacement therapy;
• Requirement for immunosuppressive therapy using systemic or absorbable topical corticosteroids (equivalent to prednisone >10mg/day) within 2 weeks prior to first dose;
• Any history or evidence of bleeding diathesis regardless of severity; grade ≥3 bleeding events per CTCAE v5.0 within 4 weeks prior to first dose; or presence of unhealed wounds, fractures, active gastrointestinal ulcers, ulcerative colitis, tumors with active bleeding, or other conditions deemed by investigators to potentially cause gastrointestinal hemorrhage or perforation;
• Patients with severe and/or uncontrolled comorbidities including:

• Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥90 mmHg);
• Unstable angina, myocardial infarction, ≥grade 2 congestive heart failure, or arrhythmias requiring treatment (including QTc ≥480ms) within 6 months prior to first dose;
• Active or uncontrolled severe infections (≥grade 2 per CTCAE);
• Clinically significant liver disease including viral hepatitis (active HBV infection with HBV DNA >1×10³ copies/mL or >500 IU/mL; HCV infection with HCV RNA >1×10³ copies/mL or >100 IU/mL), decompensated liver disease, or chronic hepatitis requiring antiviral therapy;
• HIV-positive status;
• Poorly controlled diabetes (fasting glucose ≥grade 2 per CTCAE);
• Urinalysis showing proteinuria ≥++ with 24-hour urinary protein >1.0 g;
• Administration of live vaccines within 4 weeks prior to treatment or anticipated need during study;
• Other conditions deemed by investigators to potentially lead to premature study termination, including: severe comorbidities (including psychiatric disorders) requiring concomitant therapy, significant laboratory abnormalities, or social/family factors that may compromise patient safety or data/sample collection.