Combining toripalimab and endostatin for treating stage II melanoma

Efficacy and Safety of Perioperative Toripalimab Combined With Recombinant Human Endostatin as Postoperative Adjuvant Therapy for Clinical Stage II Malignant Melanoma: A Multicenter, Single-Arm, Phase II Clinical Study

This study is testing if combining a new cancer drug with another treatment can help people with stage II melanoma live longer without their cancer coming back after surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 58 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (other)
• Drugs / interventions: prednisone, toripalimab
• Locations: 4 sites (Shanghai, Shanghai Municipality and 3 other locations)
• Trial ID: NCT06965231 on ClinicalTrials.gov

What this trial studies

This Phase II clinical trial evaluates the efficacy and safety of perioperative toripalimab, an anti-PD-1 therapy, combined with recombinant human endostatin as postoperative adjuvant therapy for patients with clinical stage II cutaneous or acral malignant melanoma. Participants will receive two cycles of toripalimab before surgery, followed by surgical tumor removal, and then continue with toripalimab and endostatin for up to 11 cycles. The study aims to determine if this combination improves 2-year recurrence-free survival compared to historical data and assesses the safety and tolerability of the treatment. It involves 58 patients across multiple hospitals in China.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with confirmed stage II cutaneous or acral malignant melanoma who have not received prior anti-tumor therapy.

Not a fit: Patients with mucosal or uveal melanoma, or those who have previously undergone anti-tumor therapy, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve recurrence-free survival rates for patients with stage II melanoma.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific combination is novel.

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.

Where this trial is running

Shanghai, Shanghai Municipality and 3 other locations

• Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (RECRUITING)
• Cancer center, Shanghai 411 hospital, China RongTong Medical Healthcare Group Co.Ltd./411 Hospital, Shanghai University — Shanghai, Shanghai Municipality, China (RECRUITING)
• Department of Surgical Oncology, Fudan University Shanghai Cancer Center Minhang Branch Hospital — Shanghai, Shanghai Municipality, China (RECRUITING)
• Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Principal investigator: Chunmeng Wang, Dr. — Fudan University
• Study coordinator: Chunmeng Wang, Dr.

Conditions: Melanoma of Skin, Acral Melanoma, Stage II Melanoma, Melanoma of skin, Acral melanoma, Stage II melanoma, Toripalimab, Recombinant human endostatin