Brief Title: Disitamab Vedotin in Subjects With HER2 Expressing Urothelial Carcinoma

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR)

Primary Outcome 1 - Timeframe: Duration of treatment; approximately 2 years

CONDITION

• Urothelial Carcinoma

ELIGIBILITY

Inclusion Criteria:
Expected survival ≥12 weeks

- Histologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
Cohorts A and B: Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy
Neoadjuvant or adjuvant systemic therapy, with progression within 12 months of completing last dose of therapy, is considered a line of prior therapy.

- Maintenance avelumab therapy delivered following first-line platinum therapy is not considered a separate line of therapy.

- Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second-line treatment is allowed
Cohort C: No prior systemic therapy for LA/mUC
Neoadjuvant or adjuvant therapy, including PD-(L1) inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy

- Cohorts A and B only: Radiographically documented disease progression during or after the most recent line of therapy for LA/mUC

- At least one measurable lesion by investigator assessment based on RECIST version 1.1.

- Cohort C only: Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation

- Participants must be able to provide archived tumor tissue prior to treatment initiation. If archival tissue is not available, a baseline biopsy is required within 28 days of Cycle 1 Day 1.

- HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
Eastern Cooperative Oncology Group (ECOG) performance status score:
Cohorts A and B: ECOG of 0 or 1

- Cohort C: ECOG of 0, 1, or 2
Exclusion Criteria:
Known hypersensitivity to disitamab vedotin, pembrolizumab (in Cohort C), or any of their components

- Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study

- Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)

- Prior MMAE-based ADCs (eg, enfortumab vedotin) or HER2-directed therapy

- Major surgery that has not fully recovered within 4 weeks prior to dose administration

- Peripheral sensory or motor neuropathy ≥ Grade 2 at baseline
Other malignant tumors within 3 years of study treatment, except for:
Prostate cancer treated with definitive intent (surgically or with radiation therapy) ≥ 1 year prior to treatment initiation is acceptable

- Malignancies that can be cured after treatment
There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

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