A Study of RC48-ADC Combined With JS001 for Advanced Extramammary Paget Disease of the Scrotum (RC48&J for EPD)

A Prospective Multicenter Clinical Trial on the Efficacy and Safety of RC48-ADC (Disitamab Vedotin) Combined With Toripalimab in Advanced HER2-positive Extramammary Paget Disease of the Scrotum

The goal of this clinical trial is to learn if Disitamab Vedotin combined with Toripalimab works to treat advanced HER2-positive extramammary Paget disease of the scrotum. It will also learn about the safety of this combination. The main questions it aims to answer are: Does this combination reduce tumor volume and delay disease progression? What medical problems do participants have when receving this combination? Participants will: Intravenous using this combination every 3 weeks until disease progression or intolerable adverse reactions occur. Visit the clinic once every 3 weeks for checkups and tests.

Study Overview

• Status: Recruiting
• Conditions: Paget Disease, Extramammary; Scrotum Disease
• Intervention / Treatment: Drug: Disitamab Vedotin combined with Toripalimab

Detailed Description

This study is a multiple-center, phase II clinical trial. Participants with HER2-positive advanced scrotal extramammary Paget's disease who met the eligibility criteria were enrolled after signing an informed consent form. All patients received treatment with 2mg/kg of Disitamab Vedotin and 3mg/kg of Toripalimab intravenous infusion every 3 weeks until disease progression. Follow-up was conducted until disease progression, intolerable adverse reactions, withdrawal of informed consent by the participant, loss to follow-up, or death. The area of the largest lesion on the scrotal skin was measured and clinical tumor imaging assessments were performed using RECIST during the treatment process.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yiming Su, Doctor; Phone Number: 86-0591-86218417; Email: suyiming@fjmu.edu.cn
• Study Contact Backup: Name: Ru Chen, Doctor; Phone Number: 86-059186218017; Email: chenru99999@126.com

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Recruiting
      • Fujian Medical University Union Hospital
      • Principal Investigator: Shaoxing Zhu, Doctor
      • Contact: Yiming Su, Doctor; Phone Number: 86-0591-86218417; Email: suyiming@fjmu.edu.cn
      • Contact: Ru Chen, Doctor; Phone Number: 86-0591-86218017; Email: chenru99999@126.com
      • Principal Investigator: Jinchao Chen, Doctor
      • Principal Investigator: Zhixian Yu, Doctor
      • Principal Investigator: Liefu Ye, Doctor
      • Principal Investigator: Zhiyang Huang, Doctor
      • Principal Investigator: Zhiming Zhuang, Doctor

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Voluntarily sign the informed consent form and comply with the requirements of the protocol.

Age ≥ 18 years old. Confirmed diagnosis by histological examination, combined with imaging assessment for scrotal extramammary Paget's disease; pathologically confirmed as HER2 positive, i.e., immunohistochemical test HER2 ≥ 1+.

ECOG score: 0 to 1. At least one measurable lesion (according to the RECIST criteria, non-nodal lesions with a longest diameter on CT scan ≥10 mm, and nodal lesions with a shortest diameter on CT scan ≥15 mm); or skin lesions that can be evaluated according to the WHO criteria.

Adequate organ function: Blood routine: Absolute Neutrophil Count (ANC) ≥1.5×10^9/L, Platelet (PLT) ≥70×10^9/L, Hemoglobin (HGB) ≥80g/L; Liver function: Total Bilirubin (TBIL) ≤1.5×Upper Limit of Normal Value (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤3×ULN; Serum Albumin ≥28 g/L; Alkaline Phosphatase (ALP) ≤5×ULN; If the subject has received routine liver protection treatment and meets the above standards, and is stable for at least one week after assessment by the researcher, they may be enrolled; Renal function: Serum Creatinine (Cr) ≤1.5×ULN, or Creatinine Clearance ≥50 mL/min (using the standard Cockcroft-Gault formula): Coagulation function: International Normalized Ratio (INR) ≤1.5 / Prothrombin Time (PT) ≤1.5×ULN, Activated Partial Thromboplastin Time (aPTT) ≤1.5×ULN; If the subject is receiving anticoagulant therapy, as long as PT and INR are within the range specified for the anticoagulant medication, it is acceptable.

Estimated life expectancy ≥3 months.

Exclusion Criteria:

Have a history of immunodeficiency, including HIV positive or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation; Have had active autoimmune diseases within 2 years prior to the start of the study treatment that required systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants), except for replacement therapies (e.g., thyroid hormone, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency); currently receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy. The dose is >10mg/day of prednisone or other equivalent hormones, and it is within 2 weeks of the first administration and still in use; Have a history of active tuberculosis; Have uncontrollable, recurrent drainage of ascites, pericardial effusion, or pleural effusion; Have undergone major organ transplantation; Received major surgical treatment, incisional biopsy, or significant traumatic injury within 28 days prior to the start of the study treatment; or have chronic non-healing wounds or fractures; Have a history of live attenuated vaccine administration within 14 days prior to the start of the study treatment or plan to receive live attenuated vaccine vaccination during the study period; Have had a severe hypersensitivity reaction after the use of monoclonal antibodies; known allergy to the active ingredients or excipients of this study drug; Within 4 weeks prior to the start of the study, are participating in or have participated in other clinical studies; Have a history of severe allergies; Have a risk of bleeding, or coagulation dysfunction, or are currently receiving -thrombolytic therapy; Have a history of substance abuse and are unable to quit or have mental disorders; According to the investigator's judgment, there are concomitant diseases that seriously endanger the safety of the subject or affect the completion of the study, or there are other reasons deemed unsuitable for enrollment by the investigator.

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: Study group; Disitamab Vedotin combined with Toripalimab

Drug: Disitamab Vedotin combined with Toripalimab; Disitamab Vedotin at a dosage of 2mg/kg and 3mg/kg of Toripalimab administered intravenously every 3 weeks (ivgtt q3w) is continued until disease progression, with the allowance for treatment discontinuation due to disease progression, death, intolerable toxicity, withdrawal of informed consent, initiation of new antineoplastic therapy, or other reasons specified in the protocol, with the earliest occurring event taking precedence. Alternatively, the study investigator may determine the need to discontinue treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	ORR includes two categories: Complete Response (CR): All target lesions in the patient have completely disappeared, and no new lesions have appeared for a certain time. Partial Response (PR): The tumor in the patient has reduced in size by at least 30%, and this reduction has been maintained for a certain period.	every 6 weeks,up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Progression-Free Survival (PFS) is a clinical endpoint used primarily in oncology to measure the effectiveness of a treatment in delaying the progression of a disease. It is defined as the length of time during which a patient's disease does not get worse after starting a treatment. PFS takes into account the time from the start of treatment until the first occurrence of disease progression, or the patient's death if it occurs before progression.	through study completion, an average of 2 year
Adverse events	adverse events	through study completion, an average of 2 year

Collaborators and Investigators

• Sponsor: Fujian Medical University Union Hospital
• Collaborators: First Affiliated Hospital of Wenzhou Medical University; Quanzhou First Hospital; Fujian Provincial Hospital; Zhangzhou Affiliated Hospital of Fujian Medical University; Zhejiang Tumor Hospital
• Investigators: Principal Investigator: Shaoxing Zhu, Doctor, Fujian Medical University Union Hospital

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 19, 2025
• First Submitted That Met QC Criteria: January 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 19, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Toripalimab; RC48-ADC; Disitamab Vedotin; extramammary Paget disease
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Neoplasms, Ductal, Lobular, and Medullary; Paget Disease, Extramammary; Immunologic Factors; Physiological Effects of Drugs; Immunoconjugates; Disitamab vedotin
• Other Study ID Numbers: 2024YF066-01; ECCO-KY-24003 (Other Grant/Funding Number: Eastern Clinical Oncology Research Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual Participant Data is protected.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No