Disitamab Vedotin with Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2

JRCT ID: jRCT2061240094

Registered date:17/12/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Urothelial Carcinoma
• Date of first enrollment: 31/03/2025
• Target sample size: 35
• Countries of recruitment: United States,Japan,Argentina,Japan,Australia,Japan,Brazil,Japan,Canada,Japan,Chile,Japan,France,Japan,Israel,Japan,Italy,Japan,Republic of Korea,Japan,Peru,Japan,Singapore,Japan,Spain,Japan,Taiwan,Japan,United Kingdom,Japan
• Study type: Interventional

Intervention(s)

Experimental Arm
- Disitamab vedotin 1.5 mg/kg administered intravenously (IV) every 2 weeks + pembrolizumab 400 mg IV every 6 weeks

Control arm
- Gemcitabine (1000 mg/m2) IV on Days 1 and 8 of every 3-week cycle + either cisplatin (70 mg/m2) IV or carboplatin (area under the plasma concentration-time curve [AUC] 4.5 or 5) IV on Day 1 of every 3-week cycle

Outcome(s)

Primary Outcome

- Progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR)
- Overall survival (OS)

Secondary Outcome

- Objective response rate (ORR) per RECIST v1.1 by BICR
- ORR per RECIST v1.1 by investigator assessment
- Duration of Response (DOR) per RECIST v1.1 by BICR
- DOR per RECIST v1.1 by investigator assessment
- Disease control rate (DCR) per RECIST v1.1 by BICR
- DCR per RECIST v1.1 by investigator assessment
- PFS per RECIST v1.1 by investigator assessment
- Number of participants with adverse events (AEs)
- Number of participants with laboratory abnormalities
- Treatment discontinuation rate due to AEs
- Number of electrocardiogram abnormalities
- Change from baseline of left ventricular ejection fraction
- Change from baseline to Week 16 in European Organization for Research and Treatment of Cancer core Quality of Life questionnaire (EORTC QLQ-C30) Global Health Status (GHS)/QoL Score
- Time to Deterioration in EORTC QLQ-C30 GHS/QoL Score
- Time to pain progression

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- 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 Response Evaluation Criteria in Solid Tumors (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

Exclude criteria

- 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 programmed cell death protein 1 and programmed death-ligand 1 (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 a monomethyl auristatin E (MMAE) agent or anti-HER2 therapy

Related Information

• Primary Sponsor: Daniel Jiang
• Secondary ID(s): NCT05911295,2022-501105-12