A Substudy of Investigational Agents in Programmed Cell Death-1/Ligand 1 (PD-1/L1) Refractory Locally Advanced or Metastatic Urothelial Carcinoma (mUC) (MK-3475-04A)

Urothelial Carcinoma Clinical Trial

Official title:

A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Study of Investigational Agents With or Without Pembrolizumab in Participants With PD-1/L1 Refractory Locally Advanced or Metastatic Urothelial Carcinoma (KEYMAKER-U04): Substudy 04A

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05562830
• Other study ID #: 3475-04A
• Secondary ID: MK-3475-04A2020-
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 16, 2022
• Est. completion date: October 28, 2027

Study information

• Verified date: June 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This substudy is part of an umbrella platform study which is designed to evaluate investigational agents with or without pembrolizumab in participants with urothelial carcinoma who are in need of new treatment options. Substudy 04A will enroll participants with locally advanced or mUC whose disease is resistant to treatment with programmed cell death-1/ligand 1 (PD-1/L1) inhibitors. The protocol infrastructure will enable the rolling assignment of investigational treatments.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 40
• Est. completion date: October 28, 2027
• Est. primary completion date: October 28, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

• Histologically or cytologically confirmed diagnosis of locally advanced/unresectable or mUC of the renal pelvis, ureter (upper urinary tract), bladder, or urethra.

• PD-1/L1 refractory locally advanced or mUC as evidenced by:

EITHER disease progression while on treatment or after treatment with an anti-PD-1/L1 monoclonal antibody (mAb) for locally advanced/unresectable or mUC administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies OR disease recurrence while on treatment or after treatment with an anti-PD-1/L1 mAb for muscle-invasive urothelial carcinoma (MIUC) administered as monotherapy.

• Participants 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.

Exclusion Criteria:

• Known additional nonurothelial malignancy that is progressing or has required active treatment within 3 years prior to study randomization/allocation.

• Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization/allocation.

• Active infection requiring systemic therapy.

• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.

• Known history of human immunodeficiency virus (HIV).

• Known history of hepatitis B or known hepatitis C virus infection.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Urothelial Carcinoma

Intervention

Biological:
• Zilovertamab vedotin
Administered via intravenous (IV) infusion on day 1 and day 8 of Q3W cycles

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si	Brisbane	Queensland
Chile	Bradfordhill-Clinical Area ( Site 1155)	Santiago	Region M. De Santiago
Chile	FALP-UIDO ( Site 1151)	Santiago	Region M. De Santiago
Denmark	Rigshospitalet-Dept. of Oncology ( Site 1701)	Copenhagen	Hovedstaden
Israel	Rambam Health Care Campus-Oncology ( Site 1501)	Haifa
Israel	Rabin Medical Center-Oncology ( Site 1504)	Petah Tikva
Israel	Sheba Medical Center-ONCOLOGY ( Site 1503)	Ramat Gan
Korea, Republic of	Asan Medical Center ( Site 1901)	Seoul
Korea, Republic of	Samsung Medical Center ( Site 1902)	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System ( Site 1903)	Seoul
Spain	Hospital Universitari Vall d'Hebron ( Site 1767)	Barcelona
Spain	Hospital Clinico San Carlos ( Site 1765)	Madrid
United States	Anschutz Cancer Pavilion ( Site 1017)	Aurora	Colorado
United States	Cleveland Clinic-Taussig Cancer Center ( Site 1036)	Cleveland	Ohio
United States	Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)	Indianapolis	Indiana
United States	University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)	Orange	California
United States	UPMC Hillman Cancer Center ( Site 1014)	Pittsburgh	Pennsylvania
United States	Washington University ( Site 1038)	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Chile,  Denmark,  Israel,  Korea, Republic of,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Experienced At Least One Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.	Up to approximately 5 years
Primary	Percentage of Participants Who Discontinued Study Treatment Due to an AE	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment	Up to approximately 5 years
Primary	Objective Response Rate (ORR)	ORR is defined as the percentage of participants who achieve a Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 2 years
Secondary	Duration of Response (DOR)	For participants who demonstrate confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented.	Up to approximately 2 years

External Links

•   Merck Oncology Clinical Trials Information