RECRUITING

A Study of Disitamab Vedotin Alone or With Pembrolizumab in Urothelial Cancer That Expresses HER2

Conditions

Urothelial Carcinoma Urothelial Cancer Bladder Cancer HER2 Mutations HER2 Overexpression HER2 Amplification RC48 Seattle Genetics

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2022-05-03

Study Completion:2028-05-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04879329

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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	* 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

Inclusion Criteria

Exclusion Criteria

* 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

* 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

Contacts and Locations

Study Contact

Seagen Trial Information Support

CONTACT

866-333-7436

clinicaltrials@seagen.com

Principal Investigator

Medical Monitor

STUDY_DIRECTOR

Seagen Inc.

Study Locations (Sites)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

United States

City of Hope

Duarte, California, 91010

United States

University of California Los Angeles Medical Center

Los Angeles, California, 90095

United States

University of California Irvine Medical Center

Orange, California, 92868

United States

Kaiser Permanente Southern California

Riverside, California, 92505

United States

University of California, San Francisco | HDFCCC - Hematopoietic Malignancies

San Francisco, California, 94158

United States

University of Colorado Health Memorial Hospital

Colorado Springs, Colorado, 80909

United States

MedStar Washington Hospital Center

Washington, District of Columbia, 20010

United States

Florida Cancer Specialists - South Region

Fort Myers, Florida, 33901

United States

Florida Cancer Specialists - Panhandle

Tallahassee, Florida, 32308

United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612

United States

Florida Cancer Specialists - East West Palm Beach, FL (SCRI)

West Palm Beach, Florida, 33401

United States

Northwest Georgia Oncology Centers, P.C.

Marietta, Georgia, 30060

United States

University of Chicago Medical Center

Chicago, Illinois, 60637

United States

Henry Ford Health System

Detroit, Michigan, 48202

United States

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48226

United States

Cancer and Hematology Centers of Western Michigan / Spectrum Health Butterworth Campus

Grand Rapids, Michigan, 49503

United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169

United States

North Shore Center for Advanced Medicine Monter Cancer Center / North Shore University Hospital

Lake Success, New York, 11042

United States

New York University (NYU) Cancer Institute

New York, New York, 10016

United States

Mount Sinai Medical Center

New York, New York, 10029

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

SUNY Upstate Medical University

Syracuse, New York, 13210

United States

Levine Cancer Institute

Charlotte, North Carolina, 28204

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106

United States

Ohio State University

Columbus, Ohio, 43210

United States

Oklahoma University at Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

University of Tennessee

Knoxville, Tennessee, 37920

United States

MD Anderson Cancer Center / University of Texas

Houston, Texas, 77030-4095

United States

Baylor Scott & White Medical Center

Temple, Texas, 76508

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

Inova Schar Cancer Institute

Fairfax, Virginia, 22031

United States

Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109

United States

Medical College of Wisconsin (Milwaukee)

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Seagen Inc.

Medical Monitor, STUDY_DIRECTOR, Seagen Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-05-03

Study Completion Date2028-05-30

Study Record Updates

Study Start Date2022-05-03

Study Completion Date2028-05-30

Terms related to this study

Keywords Provided by Researchers

Urothelial Cancer
Bladder Cancer
HER2 Mutations
HER2 Overexpression
HER2 Amplification
RC48
Seattle Genetics

Additional Relevant MeSH Terms

Urothelial Carcinoma