Home › Trials › NCT04879329

Treatment of HER2 expressing urothelial cancer with disitamab vedotin and pembrolizumab

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

Phase 2 Interventional Seagen Inc. · NCT04879329

This study is testing if a new drug called disitamab vedotin, alone or with another drug called pembrolizumab, can help shrink tumors in patients with a specific type of bladder cancer that can't be surgically removed.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment372 (estimated)
Ages18 Years and up
SexAll
SponsorSeagen Inc. Industry-sponsored
Drugs / interventionsenfortumab, pembrolizumab, disitamab, CAR-T, chemotherapy, immunotherapy, prednisone
Locations223 sites (Gilbert, Arizona and 222 other locations)
Trial IDNCT04879329 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the efficacy and safety of disitamab vedotin, either alone or in combination with pembrolizumab, for patients with HER2 expressing urothelial carcinoma. Participants will include those with locally advanced or metastatic disease that cannot be surgically removed. The study aims to assess the drug's effectiveness in shrinking tumors and to monitor any side effects experienced by the participants. The trial will involve multiple cohorts based on prior treatment history and HER2 expression levels.

Who should consider this trial

Good fit: Ideal candidates are adults with locally advanced or metastatic urothelial carcinoma that expresses HER2 and have received limited prior systemic therapy.

Not a fit: Patients with HER2 negative urothelial cancer or those who have received extensive prior treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with HER2 positive urothelial cancer.

How similar studies have performed: Other studies have shown promising results with HER2-targeted therapies in similar cancer types, suggesting potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

Cohorts A and B

* 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

Cohort C

* 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

Cohort D

* 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

Cohort E

* 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

Cohort G

* 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 Criteria:

Cohorts A and B

* 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

Cohort C

* 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.

Cohort D

* 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

Cohort E

* 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

Cohort G

* 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

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Where this trial is running

Gilbert, Arizona and 222 other locations

+173 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Urothelial CarcinomaUrothelial CancerBladder CancerHER2 MutationsHER2 OverexpressionHER2 AmplificationRC48Seattle Genetics
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.