Phase 1 Trial of CA-4948 in Combination With Pembrolizumab to Overcome Resistance to PD-1/PD-L1 Blockade in Metastatic Urothelial Cancer
National Cancer Institute (NCI)
Summary
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.
Description
PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose of the combination of CA-4948 plus pembrolizumab in patients with immune checkpoint blockade (ICB)-resistant metastatic urothelial cancer (Dose Escalation Cohort). II. To determine the safety of the combination of CA-4948 plus pembrolizumab in patients with ICB-resistant metastatic urothelial cancer (Dose Escalation Cohort and Dose Expansion Cohort). SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To measure the objective response (complete response \[CR\] or partial response \[PR\]) as defined by Resp…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Patients must have histologically confirmed urothelial cancer that is metastatic or unresectable and must have had the prior treatments outlined * Age ≥ 18 years * Because no dosing or adverse event data are currently available on the use of CA-4948 in combination with pembrolizumab in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%) within 28 days prior to registration * Leukocytes ≥ 3,000/mcL * Absolute neutrophil c…
Interventions
- ProcedureBiopsy Procedure
Undergo tumor biopsy
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureComputed Tomography
Undergo CT
- BiologicalEmavusertib
Given PO
- ProcedureMagnetic Resonance Imaging
Undergo MRI
- BiologicalPembrolizumab
Given IV
- ProcedurePositron Emission Tomography
Undergo PET
Locations (11)
- City of Hope Comprehensive Cancer CenterDuarte, California
- UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory CareIrvine, California
- UC San Diego Moores Cancer CenterLa Jolla, California
- UC Irvine Health/Chao Family Comprehensive Cancer CenterOrange, California
- University of Miami Miller School of Medicine-Sylvester Cancer CenterMiami, Florida
- Emory University Hospital MidtownAtlanta, Georgia