Clinical Trials List
Protocol NumberMK-3475-04B
NCT Number(ClinicalTrials.gov Identfier)NCT05845814
Active
2023-05-26 - 2027-07-31
Phase I/II
Recruiting3
ICD-10C68.9
Malignant neoplasm of urinary organ, unspecified
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9189.9
Malignant neoplasm of urinary organ, site unspecified
A Phase 1/2 Randomized, Umbrella Study to Evaluate the Safety and Efficacy of Pembrolizumab Plus Enfortumab Vedotin (EV) in Combination With Investigational Agents Versus Pembrolizumab Plus EV, as First-Line Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04B
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2026/03/01
Investigators and Locations
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- FU-JEN HSUEH Division of Hematology & Oncology
- CHUNG-HSIN CHEN Division of Urology
- - - Division of Urology
- 徐偉勛 醫學研究部
- JHE-CYUAN GUO Division of Hematology & Oncology
- Yu-Chieh Tsai Division of Hematology & Oncology
- Yeong-Shiau Pu Division of Urology
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Jiann-Hui Ou Division of Urology
- Shang-Yin Wu Division of Hematology & Oncology
- Jui-Hung Tsai Division of Hematology & Oncology
- Yuh-Shyan Tsai Division of Urology
- Che-Yuan Hu Division of Urology
- Wu-Chou Su Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Metastatic Urothelial Carcinoma、 Urothelial Neoplasms
Objectives
main purpose:
‧Purpose (Part 1): To evaluate subjects receiving MK-4280A plus EV (Group A), MK-7684A plus EV (Group B), and pembrolizumab plus EV (Group C) according to RECIST 1.1 ORR of the person.
‧Purpose (Part 1): To evaluate the safety and tolerability of subjects treated with MK-4280A plus EV (Arm A), MK-7684A plus EV (Arm B), and pembrolizumab plus EV (Arm C). receptive nature.
‧Purpose (Part 2): To compare EV plus MK-4280A (Group A) and/or EV plus MK 7684A (Group B) versus EV plus pembrolizumab (group C).
‧Hypothesis (H1; Part 2): EV plus MK-4280A (Arm A) and/or EV plus MK-7684A (Arm B) is superior to EV plus pembrolizumab in terms of PFS, as assessed by BICR according to RECIST 1.1 ( Group C).
Secondary purpose:
‧Purpose (Part 1): To evaluate subjects receiving MK-4280A plus EV (Group A), MK-7684A plus EV (Group B), and pembrolizumab plus EV (Group C) according to RECIST 1.1 The PFS of the person.
‧Purpose (Part 2): To compare EV plus MK-4280A (Arm A) and/or EV plus MK-7684A (Arm B) versus EV plus pembrolizumab in terms of overall survival (OS).
‧Hypothesis (H2; Part 2): EV plus MK 4280A (Arm A) and/or EV plus MK 7684A (Arm B) is superior to EV plus pembrolizumab (Arm C) in terms of OS.
‧Purpose (Part 2): To evaluate subjects receiving MK-4280A plus EV (Group A), MK-7684A plus EV (Group B), and pembrolizumab plus EV (Group C) according to RECIST 1.1 ORR of the person.
‧Purpose (Part 2): To evaluate the safety and tolerability of subjects treated with MK-4280A plus EV (Arm A), MK-7684A plus EV (Arm B), and pembrolizumab plus EV (Arm C). receptive nature.
‧Purpose (Part 1 and Part 2): To evaluate the acceptance of MK-4280A plus EV (Group A), MK-7684A plus EV (Group B) and pembrolizumab plus EV (Group C) according to RECIST 1.1 by BICR Duration of response (DOR) in treated subjects.
‧Purpose (Part 1 and Part 2): Using the European Organization for Research and Treatment of Cancer 30-Item Core Quality of Life Questionnaire (EORTC QLQ-C30) tool and the European Five Dimensions/Five Levels Quality of Life Assessment (EQ-5D-5L), Subjects who received MK-4280A plus EV (Group A), MK-7684A plus EV (Group B), and pembrolizumab plus EV (Group C) were evaluated for changes in patient-reported outcomes compared with the baseline period and before exacerbation Time elapsed (TTD).
Third/exploratory purpose
‧Purpose (Part 1 and Part 2): To evaluate the pharmacokinetics (PK) of MK-4280A plus EV (Arm A), MK 7684A plus EV (Arm B), and pembrolizumab plus EV (Arm C).
‧Purpose (Part 1 and Part 2): To assess antidrug antibody (ADA) formation in MK 4280A plus EV (Panel A), MK 7684A plus EV (Panel B), and pembrolizumab plus EV (Panel C).
‧Purpose (Parts 1 and 2): To identify clinical responses/resistance that may represent MK-4280A plus EV (Group A), MK-7684A plus EV (Group B), and pembrolizumab plus EV (Group C) Molecular (genomic, metabolic and/or proteomic) biomarkers of drug properties, safety and/or mechanism of action.
‧Purpose (Parts 1 and 2): To evaluate the efficacy of EV plus MK-4280A (Arm A) and EV plus MK-7684A (Arm C) compared to EV plus pembrolizumab (Arm C) according to RECIST 1.1 by BICR. Group B) Depth of response in treated subjects.
‧Purpose (Part 1 and Part 2): Using the EORTC QLQ-C30 tool and EQ-5D-5L, for patients receiving MK-4280A plus EV (Arm A), MK-7684A plus EV (Arm B), and pembrolizumab Adding subjects treated with EV (Group C), the changes in patient-reported results compared to the base period were evaluated.
‧Purpose (Part 2): Assessment by trial moderator according to RECIST 1.1
Test Drug
Pembrolizumab
Enfortumab Vedotin（EV）
Enfortumab Vedotin（EV）
Active Ingredient
Enfortumab Vedotin (ASG-22CE)
Pembrolizumab (Humanized anti-PD-1 mAb)
MK-7684(vibostolimab) + Pembrolizumab (MK-3475) (Humanized anti-PD-1 mAb)
Favezelimab (MK-4280) (Humanized IgG4 mAb) + Pembroli
Pembrolizumab (Humanized anti-PD-1 mAb)
MK-7684(vibostolimab) + Pembrolizumab (MK-3475) (Humanized anti-PD-1 mAb)
Favezelimab (MK-4280) (Humanized IgG4 mAb) + Pembroli
Dosage Form
Injection
Injection
Injection
Injection
Injection
Injection
Injection
Dosage
30mg/vial
100 mg/ 4mL
200mg/ 20 mL
800 mg of MK-4280 and 200 mg of pembrolizumab /40 mL
100 mg/ 4mL
200mg/ 20 mL
800 mg of MK-4280 and 200 mg of pembrolizumab /40 mL
Endpoints
‧ Objective response (OR): CR or PR.
‧ Adverse events (AE).
‧ Discontinuation of trial treatment due to AE.
‧ Dose-limiting toxicity (DLT).
‧ PFS: The time from random assignment to the first documented disease progression or death from any cause, whichever occurs first.
‧ Adverse events (AE).
‧ Discontinuation of trial treatment due to AE.
‧ Dose-limiting toxicity (DLT).
‧ PFS: The time from random assignment to the first documented disease progression or death from any cause, whichever occurs first.
Inclution Criteria
Inclusion Criteria:
Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).
Participants with mixed histology are eligible provided the urothelial component is ≥50% (and <10% plasmacytoid component)
Participants whose tumors contain any neuroendocrine component are not eligible (variant histology to be confirmed locally)
Must not have received prior systemic therapy for la/mUC. The following therapies in earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are permitted:
Participants that received neoadjuvant or adjuvant chemotherapy are permitted.
Participants who received anti- programmed cell death 1 protein (PD-1) or programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence >12 months from completion of therapy are permitted.
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 or with
Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).
Participants with mixed histology are eligible provided the urothelial component is ≥50% (and <10% plasmacytoid component)
Participants whose tumors contain any neuroendocrine component are not eligible (variant histology to be confirmed locally)
Must not have received prior systemic therapy for la/mUC. The following therapies in earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are permitted:
Participants that received neoadjuvant or adjuvant chemotherapy are permitted.
Participants who received anti- programmed cell death 1 protein (PD-1) or programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence >12 months from completion of therapy are permitted.
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 or with
Exclusion Criteria
Exclusion Criteria:
Has a known additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
Central nervous system (CNS) metastases are permitted on-study if all of the following are true: a) CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis; b) the participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment); c) participant does not have leptomeningeal disease.
Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior 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.
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 an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
Has a history of uncontrolled diabetes.
Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection (viral, bacterial, or fungal) requiring systemic therapy.
Has a known history of human immunodeficiency virus (HIV) infection.
Has hepatitis B or hepatitis C virus infection.
Has had major surgery within 4 weeks prior to first dose of study intervention.
Has had an allogenic tissue/solid organ transplant
Has a known additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
Central nervous system (CNS) metastases are permitted on-study if all of the following are true: a) CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis; b) the participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment); c) participant does not have leptomeningeal disease.
Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study intervention.
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior 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.
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 an active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy.
Has a history of uncontrolled diabetes.
Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection (viral, bacterial, or fungal) requiring systemic therapy.
Has a known history of human immunodeficiency virus (HIV) infection.
Has hepatitis B or hepatitis C virus infection.
Has had major surgery within 4 weeks prior to first dose of study intervention.
Has had an allogenic tissue/solid organ transplant
The Estimated Number of Participants
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Taiwan
20 participants
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Global
390 participants
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