Brief Title
A Study of Disitamab Vedotin Alone and With Pembrolizumab in Urothelial Cancer That Expresses HER2
Official Title
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
Brief Summary
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR)
Secondary Outcome
cORR per RECIST v1.1 by investigator assessment
Condition
Urothelial Carcinoma
Intervention
disitamab vedotin
Study Arms / Comparison Groups
Cohort A - DV monotherapy for HER2-positive tumor types
Description: Disitamab vedotin monotherapy
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
270
Start Date
May 3, 2022
Completion Date
March 31, 2026
Primary Completion Date
October 31, 2024
Eligibility Criteria
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
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Kevin Sokolowski, MD, 866-333-7436, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04879329
Organization ID
RC48G001
Responsible Party
Sponsor
Study Sponsor
Seagen Inc.
Collaborators
RemeGen Co., Ltd.
Study Sponsor
Kevin Sokolowski, MD, Study Director, Seagen Inc.
Verification Date
June 2022