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

A Phase 2 Multi-Cohort, Open-Label, Multi-Center Clinical Study Evaluating the Efficacy and Safety of Disitamab Vedotin (RC48-ADC) Alone and in Combination With Pembrolizumab in Subjects With Locally-Advanced Unresectable or Metastatic Urothelial Carcinoma That Expresses HER2


  • Org Study ID: RC48G001
  • Secondary ID: KEYNOTE-D78
  • NTC ID: NCT04879329
  • Sponsor: Seagen Inc.


This study is being done to see if a drug called disitamab vedotin, alone or with pembrolizumab, works to treat HER2 expressing urothelial cancer. It will also test how safe the drug is for participants.

Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).

It will also study what side effects happen when participants get the drug. A side effect is anything a drug does to your body besides treating the disease.

  • Overall Status
  • Start Date
    May 3, 2022
  • Phase
    Phase 2
  • Study Type


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


  • Urothelial Carcinoma


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


Name: Kevin Sokolowski, MD

Role: Study Director

Affiliation: Seagen Inc.

Overall Contact

Name: Kevin Sokolowski, MD

Phone: 866-333-7436



Facility Status Contact
Facility: Cancer and Hematology Centers of Western Michigan / Spectrum Health Butterworth Campus
Grand Rapids, Michigan 49503
United States
Status: Recruiting Contact: Principal Investigator
Eric Batts

Facility: Mount Sinai - Tisch Cancer Institute
New York, New York 10029
United States
Status: Recruiting Contact: Principal Investigator
Matthew Galsky

Facility: University of Tennessee
Knoxville, Tennessee 37920
United States
Status: Recruiting Contact: Principal Investigator
Saikrishna Gadde

Facility: Inova Health Care Services
Falls Church, Virginia 22042
United States
Status: Recruiting Contact: Principal Investigator
Jeanny Aragon-Ching