ACTIVE_NOT_RECRUITING

A Study of Efficacy and Safety of Sacituzumab Tirumotecan (MK-2870) Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab in Advanced Urothelial Carcinoma (MK-3475-04C/KEYMAKER-U04)

Conditions

Metastatic Urothelial Carcinoma Locally Advanced Urothelial Carcinoma Programmed Cell Death-1 (PD1, PD-1)Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

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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 a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04. The substudy will consist of 2 parts. Part 1 will evaluate the safety and preliminary efficacy of sacituzumab tirumotecan plus enfortumab vedotin (EV). Part 2 will be based on Part 1 results and will evaluate the efficacy, pharmacokinetics, and safety of sacituzumab tirumotecan plus EV in combination with pembrolizumab in participants with advanced urothelial carcinoma.

Official Title

A Phase 1/2 Randomized, Umbrella Study to Evaluate the Efficacy and Safety of MK-2870 Plus Enfortumab Vedotin (EV) With and Without Pembrolizumab, as Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04C

Quick Facts

Study Start:2024-07-17

Study Completion:2028-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT06483334

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
* Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC). * Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable. * Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement are eligible. * PART 1 ONLY: Participants must have received platinum-based chemotherapy for treatment of la/mUC. * PART 1 ONLY: Participants must not have received \>2 lines of therapy for la/mUC. Platinum-based chemotherapy followed by avelumab maintenance is considered 2 lines of therapy. * PART 2 ONLY: Participants must not have received prior systemic therapy for la/mUC.	* Known additional malignancy that is progressing or has required active treatment within the past 3 years. * Known active central nervous system metastases and/or carcinomatous meningitis. * Has Grade ≥2 peripheral neuropathy. * Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing. * Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea). * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease and/or serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention. * Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator. * Has a history of uncontrolled diabetes. * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. * Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention. * PART 2 ONLY: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency. * PART 2 ONLY: Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy. * Is human immunodeficiency virus (HIV)-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. * Has active Hepatitis B or Hepatitis C virus infection. * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. * Has an active infection requiring systemic therapy. * PART 2 ONLY: History of allogeneic tissue/solid organ transplant. * Has not adequately recovered from major surgery or has ongoing surgical complications.

Inclusion Criteria

Exclusion Criteria

* Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).
* Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable.
* Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement are eligible.
* PART 1 ONLY: Participants must have received platinum-based chemotherapy for treatment of la/mUC.
* PART 1 ONLY: Participants must not have received \>2 lines of therapy for la/mUC. Platinum-based chemotherapy followed by avelumab maintenance is considered 2 lines of therapy.
* PART 2 ONLY: Participants must not have received prior systemic therapy for la/mUC.

* Known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Known active central nervous system metastases and/or carcinomatous meningitis.
* Has Grade ≥2 peripheral neuropathy.
* Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing.
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea).
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease and/or serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention.
* Has active keratitis or corneal ulcerations. Superficial punctate keratitis is allowed if the disorder is being adequately treated in the opinion of the investigator.
* Has a history of uncontrolled diabetes.
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
* PART 2 ONLY: Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention. Inhaled or topical steroids are permitted in the absence of active autoimmune disease. Physiologic replacement doses of corticosteroids are permitted for participants with adrenal insufficiency.
* PART 2 ONLY: Has an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
* Is human immunodeficiency virus (HIV)-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has active Hepatitis B or Hepatitis C virus infection.
* Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
* Has an active infection requiring systemic therapy.
* PART 2 ONLY: History of allogeneic tissue/solid organ transplant.
* Has not adequately recovered from major surgery or has ongoing surgical complications.

Contacts and Locations

Principal Investigator

Medical Director

STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Locations (Sites)

University of California San Francisco HDFCCC ( Site 4044)

San Francisco, California, 94158

United States

University of Chicago Medical Center ( Site 4037)

Chicago, Illinois, 60637

United States

Indiana University Melvin and Bren Simon Cancer Center ( Site 4011)

Indianapolis, Indiana, 46202

United States

Dana-Farber Cancer Institute ( Site 4047)

Boston, Massachusetts, 02115

United States

Siteman Cancer Center ( Site 4038)

St Louis, Missouri, 63108

United States

Icahn School of Medicine at Mount Sinai ( Site 4018)

New York, New York, 10029

United States

Cleveland Clinic-Taussig Cancer Center ( Site 4036)

Cleveland, Ohio, 44195

United States

Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 4041)

Salt Lake City, Utah, 84112

United States

Collaborators and Investigators

Sponsor: Merck Sharp & Dohme LLC

Medical Director, STUDY_DIRECTOR, Merck Sharp & Dohme LLC

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 Date2024-07-17

Study Completion Date2028-03-31

Study Record Updates

Study Start Date2024-07-17

Study Completion Date2028-03-31

Terms related to this study

Keywords Provided by Researchers

Programmed Cell Death-1 (PD1, PD-1)
Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)
Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Additional Relevant MeSH Terms

Metastatic Urothelial Carcinoma
Locally Advanced Urothelial Carcinoma