Disitamab Vedotin plus bicalutamide for HER2/AR-positive scrotal Paget disease

A Prospective, Single-Arm Clinical Study of Disitamab Vedotin Combined With Bicalutamide in HER2 and AR-Expressing Scrotal Paget's Disease

This trial will test whether combining Disitamab Vedotin and bicalutamide helps adults with advanced HER2-positive, AR-positive extramammary Paget disease of the scrotum.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: prednisone, Disitamab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07117851 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional trial gives Disitamab Vedotin intravenously every two weeks combined with daily oral bicalutamide to adults with HER2-positive and AR-positive extramammary Paget disease of the scrotum. Eligible patients have histologically confirmed disease, measurable lesions by RECIST or evaluable skin lesions, ECOG 0–1, and adequate organ function. Tumor response is measured by RECIST imaging during treatment and patients are followed until disease progression, unacceptable toxicity, consent withdrawal, loss to follow-up, or death. Safety is monitored through routine labs and adverse event reporting to characterize tolerability of the combination.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed extramammary Paget disease of the scrotum that is HER2-positive and AR-positive, with ECOG 0–1, at least one measurable or evaluable lesion, and adequate organ function.

Not a fit: Patients without HER2 or AR expression, with poor performance status (ECOG ≥2), significant organ dysfunction, or those unable to travel for regular infusions are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could shrink tumors or delay progression and provide a targeted treatment option for patients with HER2/AR-positive scrotal Paget disease.

How similar studies have performed: HER2-directed antibody–drug conjugates like Disitamab Vedotin have shown activity in other HER2-positive cancers, but combining it with the antiandrogen bicalutamide for AR-positive Paget disease is largely novel with limited prior data.

Eligibility criteria

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 and/or cytological examination, combined with imaging or ultrasound assessment for mammary and extramammary Paget's disease; pathologically confirmed as HER2 positive, i.e., immunohistochemical test HER2 ≥ 1+, and AR positive, i.e., immunohistochemical test AR ≥ 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.

Where this trial is running

Shanghai, Shanghai Municipality

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Hengchuan Su

Conditions Extramammary Paget Disease; Scrotum Disease