perioperative toripalimab and endostatin for stage ii melanoma: a phase ii trial

Conditions: Melanoma of Skin; Acral Melanoma; Stage II Melanoma

Summary: this is a phase ii clinical trial to evaluate the efficacy and safety of perioperative toripalimab (anti-pd-1) combined with recombinant human endostatin (endostar) as postoperative adjuvant therapy in patients with clinical stage ii cutaneous or acral malignant melanoma. the study aims to answer: 1. does this combination improve the 2-year recurrence-free survival (2y-rfs) compared to historical data? 2. is the treatment safe and tolerable for patients? participants will: 1. receive 2 cycles of toripalimab before surgery (neoadjuvant therapy). 2. undergo surgical removal of the tumor. 3. post surgery, receive toripalimab every 2 weeks + endostar (72-hour continuous infusion every 4 weeks) for up to 6 cycles (endostar) or 11 cycles (toripalimab). 4. be monitored for tumor recurrence, side effects, and survival for up to 2 years after treatment. this is a single-arm, multicenter study involving 58 patients across several hospitals in china. results will help determine if this combination could become a new standard adjuvant therapy for stage ii melanoma.


Eligibility criteria:
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 malignant melanoma, 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: 1. 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; 2. 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; 3. coagulation: activated partial thromboplastin time (aptt), international normalized ratio (inr), and prothrombin time (pt) ≤1.5×uln; 4. doppler ultrasound assessment: left ventricular ejection fraction (lvef) ≥50%; 8. 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; 9. 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 basal cell carcinoma of skin or carcinoma in situ of cervix); 3. 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; 4. requirement for immunosuppressive therapy using systemic or absorbable topical corticosteroids (equivalent to prednisone \>10mg/day) within 2 weeks prior to first dose; 5. 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; 6. patients with severe and/or uncontrolled comorbidities including: 1. poorly controlled hypertension (sbp ≥150 mmhg or dbp ≥90 mmhg); 2. unstable angina, myocardial infarction, ≥grade 2 congestive heart failure, or arrhythmias requiring treatment (including qtc ≥480ms) within 6 months prior to first dose; 3. active or uncontrolled severe infections (≥grade 2 per ctcae); 4. 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; 5. hiv-positive status; 6. poorly controlled diabetes (fasting glucose ≥grade 2 per ctcae); 7. urinalysis showing proteinuria ≥++ with 24-hour urinary protein \>1.0 g; 7. administration of live vaccines within 4 weeks prior to treatment or anticipated need during study; 8. 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.

Keywords: melanoma of skin acral melanoma stage ii melanoma toripalimab recombinant human endostatin (endostar) perioperative immunotherapy pd-1 inhibitor anti-angiogenic therapy phase ii study