C5731001 - SGNDV-001 - KEYNOTE-D74 - An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination With Pembrolizumab Versus Chemotherapy in Subjects With Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma That Expresses HER2 (IHC 1+ and Greater)

Studio Clinico

Patologia: Carcinoma della vescica

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Histopathological confirmation of locally advanced unresectable or metastatic urothelial carcinoma (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra.
- Measurable disease by investigator assessment per RECIST v1.1.
- Participant must not have received prior systemic therapy for LA/mUC. Exception will be made for neoadjuvant or adjuvant therapy, if disease recurrence/progression occurred more than 12 months after the last dose of therapy.
- Eligible to receive cisplatin- or carboplatin-containing chemotherapy.
- Able to provide archived formalin-fixed paraffin-embedded tumor tissue blocks from a muscle-invasive or metastatic UC lesion or biopsy of metastatic UC prior to treatment initiation. If archival tissue is not available a newly obtained baseline biopsy of an accessible tumor lesion is required within 28 days of cycle 1 day 1.
- HER2 expression of 1+ or greater on immunohistochemistry (IHC).
- Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1, or 2 within 7 days prior to randomization.

Criteri di esclusione: 

- Known hypersensitivity to disitamab vedotin, cisplatin, carboplatin, gemcitabine, or pembrolizumab or any of their components.
History of severe/life threatening immune-related adverse event (irAE) with PD-(L)1 inhibitors are excluded.- Central nervous system (CNS) and/or leptomeningeal metastasis. Participants with treated CNS metastases are permitted if all of the following are met.
    - CNS metastases have been clinically stable for at least 4 weeks and baseline scans show no evidence of new or worsening CNS metastasis.
    - Participant is on a stable dose of ≤ 10 mg/day of prednisone or equivalent for at least 2 weeks.
- History of or active autoimmune disease that has required systemic treatment in the past 2 years.
- Prior treatment with an agent directed to another stimulatory or co-inhibitory T cell receptor (including but not limited to CD137 agonists, CAR-T cell therapy, CTLA-4 inhibitors, or OX-40 agonists).
- Prior solid organ or bone marrow transplantation.
- Pleural effusion or ascites with symptoms or requiring symptomatic treatment.
- Estimated life expectancy <12 week
- Prior treatment with an MMAE agent or anti-HER2 therapy.

Numero di pazienti previsti: 

32

Trattamento sperimentale: 

disitamab vedotin + pembrolizumab

Trattamento di controllo: 

gemcitabine + cisplatin OR carboplatin

Obiettivi primari dello studio: 

- Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR)
- Overall survival (OS).

Data di inizio dell'arruolamento: 09.04.2023

Data di fine dell'arruolamento: 16.05.2027

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2022-501105-12

Data di inserimento: 11.04.2025

Promotore

Seagen Inc.

Principal Investigator ITALIA

Riferimento: Dr. Info non applicabile

Telefono: 00000

Email: na@na.it

Localita: na