Perioperative Toripalimab and Endostatin for Stage II Melanoma: A Phase II Trial (FUMS-EDJS2024)

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 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.

Study Overview

• Status: Recruiting
• Conditions: Acral Melanoma; Stage II Melanoma; Melanoma of Skin
• Intervention / Treatment: Drug: Toripalimab combined with Endostar

• Study Type: Interventional
• Enrollment (Estimated): 58
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chunmeng Wang, Dr.; Phone Number: +86 13671976170; Email: cmwang1975@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Recruiting
      • Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center
      • Contact: Chunmeng Wang, Dr.; Phone Number: +86 13671976170; Email: cmwang1975@163.com
    • Shanghai, Shanghai, China, 200081
      • Recruiting
      • Cancer center, Shanghai 411 hospital, China RongTong Medical Healthcare Group Co.Ltd./411 Hospital, Shanghai University
      • Contact: Xiaolan Yin, Dr.; Phone Number: +86 13917419783; Email: yxlorchid@163.com
    • Shanghai, Shanghai, China, 200240
      • Recruiting
      • Department of Surgical Oncology, Fudan University Shanghai Cancer Center Minhang Branch Hospital
      • Contact: Hongqiang Zhang, Dr.; Phone Number: +86 18918096892; Email: 5251545@qq.com
    • Shanghai, Shanghai, China, 200336
      • Recruiting
      • Department of Oncology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Jianjun Zhang, Dr.; Phone Number: +86 18930172901; Email: robustzhang168@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Arm; Participants will: Receive 2 cycles of toripalimab before surgery (neoadjuvant therapy).; Undergo surgical removal of the tumor.; 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).; Be monitored for tumor recurrence, side effects, and survival for up to 2 years after treatment.

Drug: Toripalimab combined with Endostar; Neoadjuvant Phase: 2 doses of toripalimab (240 mg IV, Q2W) before surgery.; Surgery: Tumor resection within 2 weeks after the last neoadjuvant dose.; Adjuvant Phase: 1) Toripalimab: 240 mg IV every 2 weeks (up to 11 cycles); 2) Endostar: 210 mg (72-hour continuous IV infusion) every 4 weeks (up to 6 cycles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year recurrence-free survival rate (2-year RFS rate)	From enrollment to the end of the 2nd year of follow-up

Secondary Outcome Measures

Outcome Measure	Time Frame
1-year distant metastasis-free survival rate (1-year DMFS rate)	From enrollment to the end of the 1st year
Overall survival (OS)	Through study completion, an average of 3 years
1-year recurrence-free survival rate (1-year RFS rate)	From enrollment to the end of the 1st year
2-year distant metastasis-free survival rate (2-year DMFS rate)	From enrollment to the end of the 2nd year

Collaborators and Investigators

• Sponsor: Fudan University
• Collaborators: Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine; Fudan University Shanghai Cancer Center Minhang Branch Hospital; Shanghai 411 hospital
• Investigators: Principal Investigator: Chunmeng Wang, Dr., Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): March 30, 2029

Study Registration Dates

• First Submitted: April 18, 2025
• First Submitted That Met QC Criteria: May 7, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 7, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Phase II study; Acral melanoma; Toripalimab; PD-1 inhibitor; Stage II melanoma; Anti-angiogenic therapy; Melanoma of skin; Recombinant human endostatin (Endostar); Perioperative immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma, Cutaneous Malignant; Melanoma; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Endostar protein
• Other Study ID Numbers: IRB2501312-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided yet.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No