A Study of Disitamab Vedotin for HER2-Expressing Urothelial Cancer
This study is looking at a drug called disitamab vedotin, either alone or with pembrolizumab, to treat urothelial cancer that has spread and expresses HER2 (a protein found on some cancer cells). You might be able to join if you have locally advanced (spread near where it started and can't be removed) or metastatic (spread through the body) urothelial cancer and have already received one or two prior treatments. The study aims to see how well these drugs work by measuring how much your tumor shrinks, and also to understand any side effects you might experience. The goal is to find out if these treatments are safe and effective for this type of cancer.
- Study design
- This study plans to enroll 372 participants. It is an interventional study, meaning participants will receive specific treatments.
- What's involved
- Disitamab vedotin is given into the vein every 2 weeks. Pembrolizumab is given into the vein on Day 1 of each 6-week cycle.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will measure how well the treatment works and track side effects for approximately 2 years.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04879329
A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2
Recruiting
PHASE2Ages 18+InterventionalTreatmentSeagen, a wholly owned subsidiary of Pfizer
~372 participants
Updated 2026-07-22 on ClinicalTrials.gov
What's tested:disitamab vedotinpembrolizumab
At a glance
Recruiting sites
169 of 221 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) (Cohorts A, B, C, and G)
Measured over Duration of treatment; approximately 2 years
+9 more outcomes measured
Conditions
Where it's being run
221 sites across 49 statesCalifornia62
Florida22
North Carolina13
New York11
Michigan10
Illinois8
Georgia7
United Kingdom7
Study leadership
- Pfizer CT.gov Call Center · STUDY_DIRECTOR · Pfizer
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of platinum-containing chemotherapy
At least one measurable lesion by investigator assessment based on RECIST version 1.1.
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 of 0 or 1
Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
No prior systemic therapy for LA/mUC
Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy
At least one measurable lesion by investigator assessment based on RECIST v1.1.
Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, on the provided tumor tissue sample
ECOG performance status of 0, 1, or 2
Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
Based on a participant's eligibility to receive treatment with standard of care therapies in Japan, participants must have received all of the following lines of therapy for LA/mUC:
a. One prior line of platinum-containing chemotherapy.
b. Prior therapy with PD-(L)1 inhibitors as (neo)adjuvant therapy, first-line maintenance therapy or as second line treatment.
c. Prior enfortumab vedotin therapy.
At least one measurable lesion by investigator assessment based on RECIST v1.1.
ECOG performance status of 0 or 1
Histopathologically-confirmed LA/mUC, including UC originating from the renal pelvis, ureters, bladder, or urethra
No prior systemic therapy for LA/mUC
Neoadjuvant or adjuvant therapy, including PD-(L)1 inhibitors, is acceptable, if disease recurrence/progression occurred more than 12 months after the last dose of systemic therapy.
At least one measurable lesion by investigator assessment based on RECIST v1.1.
Participant is eligible to receive cisplatin- or carboplatin- containing chemotherapy per investigator evaluation
HER2-expression status determined by the central laboratory to be IHC 1+, 2+ or 3+, in the provided tumor sample
ECOG performance status of 0 or 1
Histopathologically-confirmed, locally-advanced, unresectable or metastatic urothelial cancer (LA/mUC), including UC originating from the renal pelvis, ureters, bladder, or urethra
Participants must have received only 1 or 2 lines of prior systemic treatment for LA/mUC, including 1 line of therapy containing enfortumab vedotin as monotherapy or in combination with pembrolizumab
The last administration of enfortumab vedotin must be 90 days from the start of study treatment. Intervening therapies are allowed between the final dose of enfortumab vedotin and the start of disitamab vedotin.
At least one measurable lesion by investigator assessment based on RECIST version 1.1.
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 of 0 or 1
Exclusion
Known hypersensitivity to disitamab vedotin or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohorts A and B)
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
Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study defined as Cycle 1 Day 1 for the single-arm part of Cohort C and as randomization date for the randomized part of Cohort C)
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
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
Participants who have previously received any 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) are excluded.
Known hypersensitivity to disitamab vedotin or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort D)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Prior HER2-directed therapy
Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy
Major surgery that has not fully recovered within 4 weeks prior to dose administration
Peripheral sensory or motor neuropathy ≥ Grade 1 at baseline
Known hypersensitivity to disitamab vedotin, pembrolizumab, or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort E)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Any prior history of ≥ Grade 3 non-hematological AEs related to prior therapy
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 1 at baseline
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study drug
Known hypersensitivity to disitamab vedotin or any of their components
Prior antitumor treatment (including chemotherapy, radiotherapy, targeted therapy, immunotherapy etc.) within 2 weeks of start of study (defined as Cycle 1 Day 1 for Cohort G)
Toxicity from a previous treatment has not returned to Grades 0 or 1 (except for Grade 2 alopecia)
Prior 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
What this trial measures
- Confirmed Objective Response Rate (cORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) by blinded independent central review (BICR) (Cohorts A, B, C, and G)Duration of treatment; approximately 2 years
The proportion of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1
- Incidence of adverse events (AEs) (Cohorts D and E)Approximately 2 years
Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment.
- Incidence of dose alterations (Cohorts D and E)Approximately 2 years
- Incidence of laboratory abnormalities (Cohorts D and E)Approximately 2 years
To be summarized using descriptive statistics.
- Incidence of electrocardiogram (ECG) abnormalities (Cohorts D and E)Approximately 2 years
- Change from baseline of left ventricular ejection fraction (LVEF) (Cohorts D and E)Approximately 2 years
- Pharmacokinetic (PK) parameter - Area under the curve (AUC) (Cohorts D and E)Through 30-37 days following the last dose of DV; up to approximately 2 years
To be summarized using descriptive statistics.
- PK parameter - Maximum concentration (Cmax) (Cohorts D and E)Through 30-37 days following the last dose of DV; up to approximately 2 years
To be summarized using descriptive statistics.
- PK parameter - Time to maximum concentration (Tmax) (Cohorts D and E)Through 30-37 days following the last dose of DV; up to approximately 2 years
To be summarized using descriptive statistics.
- PK parameter - Trough concentration (Ctrough) (Cohorts D and E)Through 30-37 days following the last dose of DV; up to approximately 2 years
To be summarized using descriptive statistics.