A Study of RC48-ADC Combined With JS001 for Advanced Extramammary Paget Disease of the Scrotum

Phase 2

Recruiting

• Conditions: Paget Disease, Extramammary; Scrotum Disease
• Interventions: Drug: Disitamab Vedotin combined with Toripalimab

• Registration Number: NCT06791070
• Lead Sponsor: Fujian Medical University Union Hospital

Brief Summary

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.

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 Timeline

• Status Verified: 2025-01
• Study Start: 2025-01
• Study First Submitted: 2025-01-19
• Study First Submitted QC: 2025-01-19
• Last Update Submitted: 2025-01-19
• Study First Posted: 2025-01-24
• Last Update Posted: 2025-01-24
• Primary Completion: 2027-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Study group	Disitamab Vedotin combined with Toripalimab	Disitamab Vedotin combined with Toripalimab

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	every 6 weeks,up to 24 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Progression free survival	through study completion, an average of 2 year	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.
Adverse events	through study completion, an average of 2 year	adverse events

Trial Locations

Locations (1)

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China