Actively Recruiting
Pembrolizumab Plus CA-4948 for the Treatment of Patients With Progressive Metastatic Urothelial Cancer Despite Prior Immunotherapy
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
27
Participants Needed
11
Research Sites
108 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This phase I trial tests the safety, side effects, best dose, and effectiveness of emavusertib (CA-4948) in combination with pembrolizumab in treating patients with urothelial cancer that has spread from where it first started to other places in the body (metastatic) and that has a resistance to PD-1/PD-L1 immune checkpoint inhibitors. CA-4948, a kinase inhibitor, may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving CA-4948 in combination with pembrolizumab may be safe, tolerable and/or effective in treating patients with metastatic urothelial cancer that is resistant to PD-1/PD-L1 immune checkpoint inhibitors.
CONDITIONS
Official Title
Pembrolizumab Plus CA-4948 for the Treatment of Patients With Progressive Metastatic Urothelial Cancer Despite Prior Immunotherapy
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must have histologically confirmed metastatic or unresectable urothelial cancer
- Age 18 years or older
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 within 28 days prior to registration
- Leukocyte count of at least 3,000/mcL
- Absolute neutrophil count (ANC) of at least 1,500/mcL
- Platelet count of at least 100,000/mcL
- Hemoglobin level of at least 9 g/dL without recent red blood cell transfusion
- Creatine phosphokinase less than or equal to grade 2
- Creatinine less than 1.5 times institutional upper limit of normal or creatinine clearance of at least 30 mL/min
- Total bilirubin less than or equal to 1.5 times institutional upper limit of normal
- AST and ALT less than or equal to 3 times upper limit of normal
- INR or prothrombin time less than or equal to 1.5 times upper limit of normal unless on therapeutic anticoagulants
- aPTT less than or equal to 1.5 times upper limit of normal unless on therapeutic anticoagulants
- Ability to provide tumor tissue samples or undergo biopsy
- Measurable metastatic or unresectable disease
- Prior treatment with a PD-1 or PD-L1 inhibitor
- Prior treatment with platinum-based chemotherapy or enfortumab vedotin
- Primary resistance to PD-1/PD-L1 blockade as defined by specific treatment and progression criteria
- Negative pregnancy test for females of childbearing potential and agreement to use contraception
- Agreement to use contraception for males of childbearing potential
- HIV-infected patients on effective therapy with undetectable viral load within 6 months
- Patients vaccinated for COVID-19 and influenza allowed
- Patients with stable, previously treated brain metastases allowed
- Patients with prior or concurrent malignancy not interfering with study allowed
- Willingness and ability to swallow pills
- Ability to understand and sign informed consent
You will not qualify if you...
- Patients with unresolved toxicities greater than grade 1 from prior cancer therapy except certain neuropathy or alopecia
- Diagnosis of immunodeficiency or use of high-dose systemic steroids or immunosuppressive therapy within 7 days prior to study drug
- Grade 3 or higher immune-related adverse events from prior PD-1/PD-L1 therapy
- History of allergic reactions to CA-4948 or pembrolizumab analogs
- Uncontrolled illnesses including lung disease, heart failure, unstable angina, or arrhythmia
- Receiving other investigational agents
- Presence of carcinomatous meningitis
- Malabsorption syndrome or conditions interfering with intestinal absorption
- Active autoimmune disease requiring systemic treatment in past 2 years
- History or current pneumonitis requiring steroids
- Conditions or lab abnormalities that could interfere with study participation
- Receipt of live vaccine within 30 days before treatment
- Pregnant or breastfeeding women
- Known active hepatitis B or C infection
- History of active tuberculosis
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 11 locations
1
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010
Actively Recruiting
2
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine, California, United States, 92612
Actively Recruiting
3
UC San Diego Moores Cancer Center
La Jolla, California, United States, 92093
Actively Recruiting
4
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
Actively Recruiting
5
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States, 33136
Actively Recruiting
6
Emory University Hospital Midtown
Atlanta, Georgia, United States, 30308
Actively Recruiting
7
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States, 30322
Actively Recruiting
8
Emory Saint Joseph's Hospital
Atlanta, Georgia, United States, 30342
Actively Recruiting
9
Mount Sinai Hospital
New York, New York, United States, 10029
Actively Recruiting
10
NYP/Weill Cornell Medical Center
New York, New York, United States, 10065
Actively Recruiting
11
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, United States, 75390
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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