KEYMAKER-U04 Substudy 04D: A Clinical Study of New Treatments Given With Enfortumab Vedotin and Pembrolizumab in People With Urothelial Cancer (MK-3475-04D/KEYMAKER-U04)

Официальное название

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents in Combination With Enfortumab Vedotin Plus Pembrolizumab as First-Line Treatment in Participants With Locally Advanced or Metastatic Urothelial Carcinoma: KEYMAKER-U04-Substudy 04D

Обзор

Researchers are looking for new ways to treat people with urothelial cancer (UC) that is locally advanced or metastatic. The standard treatment for locally advanced or metastatic UC is enfortumab vedotin (EV) given with pembrolizumab. The goals of this study are to learn about: * The safety of the study treatment when given with standard treatment and if people tolerate it * The number of people who have the cancer respond (cancer gets smaller or goes away) with the new study treatment when given with standard treatment.

Подробное описание

This is a substudy of the master protocol MK-3475-U04 (KEYMAKER-U04)

Вмешательства

• Препарат MK-3120
  Administered via intravenous (IV) infusion on day 1 and day 8 of each 3-week cycle
• Препарат EV
  Administered via IV infusion on day 1 and day 8 of each 3-week cycle
• Биопрепарат Pembrolizumab
  Administered via IV infusion on day 1 of each 3-week cycle
• Препарат Rescue Medication
  Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medication is Granulocyte Colony-Stimulating Factor (G-CSF).

Первичные конечные точки

• Number of Participants Who Experience an Adverse Event (AE) [Срок оценки: Up to approximately 27 months]
• Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [Срок оценки: Up to approximately 21 days]
• Number of Participants Who Discontinue Study Treatment Due to an AE [Срок оценки: Up to approximately 24 months]
• Objective Response Rate (ORR) as Assessed by Investigator [Срок оценки: Up to approximately 58 months]

Вторичные конечные точки (12)

• Duration of Response (DOR) as Assessed by Investigator [Срок оценки: Up to approximately 58 months]
• Serum Maximum Concentration (Cmax) of MK-3120 Antibody-Drug Conjugate (ADC) [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Serum Trough Concentration (Ctrough) of MK-3120 ADC [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Serum Cmax of MK-3120 Total Antibodies (TAb) [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Serum Ctrough of MK-3120 TAb [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Plasma Cmax of MK-3120 Free Payload [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Plasma Ctrough of MK-3120 Free Payload [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Serum Cmax of EV ADC [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Serum Ctrough of EV ADC [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Serum Cmax of EV TAb [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Serum Ctrough of EV TAb [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]
• Plasma Cmax of EV Free Payload [Срок оценки: Predose and at designated time points post-dose (up to approximately 24 months)]

Критерии участия

Критерии включения

The main inclusion criteria include but are not limited to the following:

• Has histologically documented urothelial carcinoma (UC) that is locally advanced and unresectable or metastatic
• Must provide a newly obtained or archival tumor tissue sample (core or excisional biopsy)
• Must not have received prior systemic therapy for locally advanced or metastatic UC
• If infected with Human Immunodeficiency Virus (HIV), has well controlled HIV on antiretroviral therapy
• If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load before randomization
• If participant has a history of hepatitis C virus (HCV), has undetectable HCV viral load before randomization

Критерии исключения

The main exclusion criteria include but are not limited to the following:

• Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing
• Has active keratitis or corneal ulcerations
• 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 within the 6 months preceding study intervention
• Has a history of uncontrolled diabetes
• Has pleural effusion, ascites, and/or pericardial effusion that are symptomatic or require repeated drainage
• Has active autoimmune disease that has required systemic treatment in the past 2 years
• Has known additional malignancy that is progressing or has required active treatment within the past 2 years
• Has known active central nervous system metastases and/or carcinomatous meningitis
• 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
• If infected with HIV, has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has concurrent active HBV and HCV infection
• Has a history of stem cell/solid organ transplant

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 4 центра

• UCSF Medical Center at Mission Bay ( Site 5044) — San Francisco
• University of Chicago Medical Center ( Site 5037) — Chicago
• Cleveland Clinic Taussig Cancer ( Site 5036) — Cleveland
• Huntsman Cancer Institute ( Site 5041) — Salt Lake City

South Korea · 3 центра

• Severance Hospital, Yonsei University Health System ( Site 5903) — Seoul
• Asan Medical Center ( Site 5901) — Seoul
• Samsung Medical Center ( Site 5902) — Seoul

Израиль · 2 центра

• Rambam Health Care Campus ( Site 5501) — Haifa
• Rabin Medical Center ( Site 5504) — Petah Tikva

Нидерланды · 2 центра

• Nederlands Kanker Instituut Antoni van Leeuwenhoek (NKI AVL) ( Site 5302) — Amsterdam
• Erasmus MC ( Site 5303) — Rotterdam

Испания · 2 центра

• Hospital Universitari Vall de Hebron ( Site 5767) — Barcelona
• Hospital Clinico San Carlos ( Site 5765) — Madrid

Чили · 1 центр

• FALP ( Site 5151) — Santiago

Франция · 1 центр

• CHU de Bordeaux Hop St ANDRE ( Site 5607) — Bordeaux

Великобритания · 1 центр

• St Bartholomew s Hospital ( Site 5206) — London

Идентификаторы

NCT: NCT07232602 · 3475-04D · U1111-1322-3713 · 2025-522253-19-00 · MK-3475-04D

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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