Clinical trial NCT05562830: 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)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Urothelial Carcinoma
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2022-10-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Experienced At Least One Adverse Event (AE)
timeFrame: Up to approximately 5 years
measure: Percentage of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 5 years
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Duration of Response (DOR)
timeFrame: Up to approximately 2 years
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 1045)
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion ( Site 1017)
state: Colorado
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center ( Site 1011)
state: Indiana
city: Saint Louis
country: United States
facility: Washington University ( Site 1038)
state: Missouri
city: Cleveland
country: United States
facility: Cleveland Clinic-Taussig Cancer Center ( Site 1036)
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center ( Site 1014)
state: Pennsylvania
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
state: Queensland
city: Santiago
country: Chile
facility: FALP-UIDO ( Site 1151)
state: Region M. De Santiago
city: Santiago
country: Chile
facility: Bradfordhill-Clinical Area ( Site 1155)
state: Region M. De Santiago
city: Copenhagen
country: Denmark
facility: Rigshospitalet-Dept. of Oncology ( Site 1701)
state: Hovedstaden
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 1501)
city: Petah Tikva
country: Israel
facility: Rabin Medical Center-Oncology ( Site 1504)
city: Ramat Gan
country: Israel
facility: Sheba Medical Center-ONCOLOGY ( Site 1503)
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System ( Site 1903)
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center ( Site 1901)
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center ( Site 1902)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron ( Site 1767)
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos ( Site 1765)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: