Pembrolizumab Plus CA-4948 for the Treatment of Patients With Progressive Metastatic Urothelial Cancer Despite Prior Immunotherapy
Trial Parameters
Brief 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.
Eligibility Criteria
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 count (ANC) ≥ 1,500/mcL * Platelets ≥ 100,000/mcL * Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L * Criteria must be met without packed red blood cell (pRBC) transfusion within the prior 2 weeks. Participants can be on stable dose of erythropoietin (≥ approximately 3 months) * Creatine phosphokinase (CPK) \< grade (Gr) 2 ( \</= 2.5 upper limit of normal \[ULN\]) * Creatinine \< 1.5 × institutional ULN or creatin