Brief Title: Disitamab Vedotin With Pembrolizumab vs Chemotherapy in Previously Untreated Urothelial Cancer Expressing HER2

PRIMARY OUTCOMES

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

Primary Outcome 1 - Timeframe: Approximately 3 years

Primary Outcome 2 - Measure: Overall survival (OS)

Primary Outcome 2 - Timeframe: Approximately 5 years

CONDITION

• Urothelial Carcinoma

ELIGIBILITY

Inclusion 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 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.
Exclusion 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 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Kevin Sokolowski, MD

Role: Study Director

Affiliation: Seagen Inc.

Overall Contact

Name: Kevin Sokolowski, MD

Phone: 866-333-7436

Email: clinicaltrials@seagen.com

LOCATION