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New treatment option for Metastatic Urothelial Carcinoma
Official title Pembrolizumab Plus CA-4948 for the Treatment of Patients With Progressive Metastatic Urothelial Cancer Despite Prior Immunotherapy
ClinicalTrials.gov ID: NCT06439836
What this study is testing
What is Emavusertib?
Emavusertib is an investigational medicine, given as an once-daily infusion into a vein, being studied as a potential treatment for metastatic urothelial carcinoma.
Also referred to as AU 4948, AU-4948.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- 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.
- Phase 1: an early, usually small safety study
- Time commitment: about 2 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- 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...
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%) within 28 days prior to registration
- Leukocytes ≥ 3,000/mcL
You likely can't join if
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) Note: Patients with...
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any...
- Grade ≥ 3 immune related adverse event with prior PD-1/PD-L1 blockade
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CA-4948 and/or pembrolizumab
- Patients with uncontrolled intercurrent illness, including but not limited to interstitial lung disease or active, non-infectious pneumonitis...
- Patients who are receiving any other investigational agents
See the full eligibility criteria
Who can join
- 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...
- 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 creatinine clearance of ≥ 30 mL/min for patient with creatine levels ≥ 1.5 x institutional ULN
- Creatinine clearance (CrCl) should be calculated per institutional standard
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) ≤ 3 x ULN
- Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) ≤ 3 x ULN
- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use...
- Activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Ability to provide at least 20 unstained slides or formalin-fixed paraffin-embedded (FFPE) block plus 1 hematoxylin and eosin (H\&E) slide from prior archival invasive urothelial cancer specimen (and/or ability to...
- Measurable metastatic or unresectable disease
- Must have received prior treatment with a PD-1 or PD-L1 inhibitor
- Must have received at least one of the following (may have been administered concurrently or sequentially with PD-1/PD-L1 inhibitor):
- Platinum-based chemotherapy
- Enfortumab vedotin
- Primary resistance to PD-1/PD-L1 blockade as defined by Society for Immunotherapy of Cancer (SITC) consensus definitions:
- For patients who received single-agent PD-1/PD-L1 blockade in the adjuvant setting:
- Must have received ≥ 6 weeks of treatment with PD-1/PD-L1 blockade
- Recurrence while on treatment or within ≤ 3 months after completion of therapy
- For patients who received single-agent PD-1/PD-L1 blockade in the metastatic setting:
- Must have received ≥ 6 weeks of treatment with PD-1/PD-L1 blockade
- Progression within ≤ 6 months of initiating treatment with single-agent PD-1/PD-L1 blockade with best response of stable disease
- For patients who received single-agent PD-1/PD-L1 blockade in the switch-maintenance setting:
- Must have received ≥ 6 weeks of treatment with PD-1/PD-L1 blockade
- Progression within ≤ 6 months of initiating treatment with single-agent PD-1/PD-L1 blockade
- For patients who received an antibody-drug conjugate or cytotoxic chemotherapy plus PD-1/PD-L1 blockade combination
- Must have received ≥ 6 weeks of treatment with PD-1/PD-L1 blockade
- Progression within ≤ 12 months of initiating treatment
- An eligibility form will be developed to include documentation of the dates of prior PD-1/PD-L1 blockade and a redacted radiology report confirming best response of stable disease for \< 6 months or progressive disease)
- Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as...
- Male patients of childbearing potential must agree to use an adequate method of contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is...
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- Patients who have received messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) and influenza vaccines will be allowed
- Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either magnetic resonance...
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen
- Patients should be willing and able to swallow pills
- Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants
What rules you out
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) Note: Patients with grade ≤ 2 neuropathy or grade ≤ 2 alopecia are an exception to this...
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose...
- Grade ≥ 3 immune related adverse event with prior PD-1/PD-L1 blockade
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CA-4948 and/or pembrolizumab
- Patients with uncontrolled intercurrent illness, including but not limited to interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, or cardiac...
- Patients who are receiving any other investigational agents
- Patients with carcinomatous meningitis
- Patients with malabsorption syndrome or other conditions that would interfere with intestinal absorption
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine...
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is...
- Has received a live vaccine within 30 days of planned treatment start. Seasonal flu vaccines that do not contain live virus are permitted
- Pregnant women are excluded from this study because pembrolizumab is a monoclonal antibody with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events...
- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] RNA [qualitative] is detected)
- Has a known history of active tuberculosis (TB)
The study team makes the final eligibility decision.
Where it's taking place
- Duarte, California, United States
- Irvine, California, United States
- La Jolla, California, United States
- Orange, California, United States
- Miami, Florida, United States
- Atlanta, Georgia, United States
- New York, New York, United States
- Dallas, Texas, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The study runs about 2 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Duarte, California, United States; Irvine, California, United States; La Jolla, California, United States; Orange, California, United States; Miami, Florida, United States; Atlanta, Georgia, United States and 2 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.