Pembrolizumab Plus CA-4948 for the Treatment of Patients With Progressive Metastatic Urothelial Cancer Despite Prior Immunotherapy
NCT ID: NCT06439836
Last Updated: 2025-11-10
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
RECRUITING
Clinical Phase
PHASE1
Total Enrollment
27 participants
Study Classification
INTERVENTIONAL
Study Start Date
2025-05-05
Study Completion Date
2027-06-01
Brief Summary
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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.
Detailed Description
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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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 9 weeks and the best overall response (CR or PR) as defined by RECIST 1.1 at any time while on study.
III. To determine progression-free survival, overall survival, and duration of response.
IV. To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in 2IR scores (as defined by ribonucleic acid \[RNA\] sequencing) in paired tumor biopsies.
EXPLORATORY OBJECTIVES:
I. To assess the clinical benefit rate with pembrolizumab plus CA-4948 therapy. II. To assess the "C-reactive protein (CRP) response rate" as defined by the proportion of patients achieving a ≥ 1.5 fold reduction in CRP at 9 weeks.
III. To explore the association between the 2IR score as defined by bulk-ribonucleic acid (RNA) sequencing of pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
IV. To explore whether CA-4948 plus pembrolizumab leads to on-treatment changes in the cellular and/or molecular composition of the tumor microenvironment (TME).
V. To explore the association between the quantity and spatial localization of SPP1+ monocytes-macrophages (MoMacs) defined by multiplex immunohistochemistry on pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
VI. To explore the association between the cellular and molecular composition of the TME defined by spatial RNA sequencing on pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
VII. To explore on-treatment changes in high-sensitivity (hs) CRP and cytokines and chemokines in peripheral blood and their association with objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
VIII. To explore the association between PD-L1 expression on pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
IX. To explore the association between the CXCL9:SPP1 ratio as defined by bulk-RNA sequencing of pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
X. To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in the CXCL9:SPP1 ratio (as defined by RNA sequencing) in paired tumor biopsies.
OUTLINE: This is a dose-escalation study of CA-4948 in combination with pembrolizumab followed by a dose-expansion study.
Patients receive CA-4948 orally (PO) twice daily (BID) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) throughout the study. Additionally, patients may undergo a tumor biopsy on study.
After completion of study treatment, patients are followed up every 3 months for 2 years.
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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 at 9 weeks and the best overall response (CR or PR) as defined by RECIST 1.1 at any time while on study.
III. To determine progression-free survival, overall survival, and duration of response.
IV. To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in 2IR scores (as defined by ribonucleic acid \[RNA\] sequencing) in paired tumor biopsies.
EXPLORATORY OBJECTIVES:
I. To assess the clinical benefit rate with pembrolizumab plus CA-4948 therapy. II. To assess the "C-reactive protein (CRP) response rate" as defined by the proportion of patients achieving a ≥ 1.5 fold reduction in CRP at 9 weeks.
III. To explore the association between the 2IR score as defined by bulk-ribonucleic acid (RNA) sequencing of pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
IV. To explore whether CA-4948 plus pembrolizumab leads to on-treatment changes in the cellular and/or molecular composition of the tumor microenvironment (TME).
V. To explore the association between the quantity and spatial localization of SPP1+ monocytes-macrophages (MoMacs) defined by multiplex immunohistochemistry on pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
VI. To explore the association between the cellular and molecular composition of the TME defined by spatial RNA sequencing on pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
VII. To explore on-treatment changes in high-sensitivity (hs) CRP and cytokines and chemokines in peripheral blood and their association with objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
VIII. To explore the association between PD-L1 expression on pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
IX. To explore the association between the CXCL9:SPP1 ratio as defined by bulk-RNA sequencing of pre-treatment tumor tissue and objective response rate, clinical benefit rate, progression-free survival, and/or overall survival.
X. To assess whether CA-4948 plus pembrolizumab leads to on-treatment increases in the CXCL9:SPP1 ratio (as defined by RNA sequencing) in paired tumor biopsies.
OUTLINE: This is a dose-escalation study of CA-4948 in combination with pembrolizumab followed by a dose-expansion study.
Patients receive CA-4948 orally (PO) twice daily (BID) on days 1-21 and pembrolizumab intravenously (IV) over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) throughout the study. Additionally, patients may undergo a tumor biopsy on study.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Conditions
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Metastatic Urothelial Carcinoma
Unresectable Urothelial Carcinoma
Study Design
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Allocation Method
NA
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
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Treatment (CA-4948, pembrolizumab)
Patients receive CA-4948 orally PO BID on days 1-21 and pembrolizumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, CT, MRI, or PET throughout the study. Additionally, patients may undergo a tumor biopsy on study.
Group Type
EXPERIMENTAL
Biopsy Procedure
Intervention Type
PROCEDURE
Undergo tumor biopsy
Biospecimen Collection
Intervention Type
PROCEDURE
Undergo blood sample collection
Computed Tomography
Intervention Type
PROCEDURE
Undergo CT
Emavusertib
Intervention Type
BIOLOGICAL
Given PO
Magnetic Resonance Imaging
Intervention Type
PROCEDURE
Undergo MRI
Pembrolizumab
Intervention Type
BIOLOGICAL
Given IV
Positron Emission Tomography
Intervention Type
PROCEDURE
Undergo PET
Interventions
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Biopsy Procedure
Undergo tumor biopsy
Intervention Type
PROCEDURE
Biospecimen Collection
Undergo blood sample collection
Intervention Type
PROCEDURE
Computed Tomography
Undergo CT
Intervention Type
PROCEDURE
Emavusertib
Given PO
Intervention Type
BIOLOGICAL
Magnetic Resonance Imaging
Undergo MRI
Intervention Type
PROCEDURE
Pembrolizumab
Given IV
Intervention Type
BIOLOGICAL
Positron Emission Tomography
Undergo PET
Intervention Type
PROCEDURE
Other Intervention Names
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Biopsy
BIOPSY_TYPE
Bx
Biological Sample Collection
Biospecimen Collected
Specimen Collection
CAT
CAT Scan
Computed Axial Tomography
Computerized Axial Tomography
Computerized axial tomography (procedure)
Computerized Tomography
Computerized Tomography (CT) scan
CT
CT Scan
Diagnostic CAT Scan
Diagnostic CAT Scan Service Type
tomography
AU 4948
AU-4948
CA 4948
CA-4948
CA4948
Interleukin-1 Receptor-associated Kinase 4 Inhibitor CA-4948
IRAK4 Inhibitor CA-4948
Magnetic Resonance
Magnetic Resonance Imaging (MRI)
Magnetic resonance imaging (procedure)
Magnetic Resonance Imaging Scan
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
MR
MR Imaging
MRI
MRI Scan
MRIs
NMR Imaging
NMRI
Nuclear Magnetic Resonance Imaging
sMRI
Structural MRI
BCD-201
GME 751
GME751
Keytruda
Lambrolizumab
MK 3475
MK-3475
MK3475
Pembrolizumab Biosimilar BCD-201
Pembrolizumab Biosimilar GME751
Pembrolizumab Biosimilar QL2107
Pembrolizumab Biosimilar RPH-075
Pembrolizumab Biosimilar SB27
QL2107
RPH 075
RPH-075
RPH075
SB 27
SB-27
SB27
SCH 900475
SCH-900475
SCH900475
Medical Imaging, Positron Emission Tomography
PET
PET Scan
Positron emission tomography (procedure)
Positron Emission Tomography Scan
Positron-Emission Tomography
PT
Eligibility Criteria
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Inclusion Criteria
* Patients must have histologically confirmed urothelial cancer that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
* 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 \[ULN\])
* Measured or calculated creatinine clearance (CrCl) ≥ 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 of anticoagulants
* 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 undergo baseline tumor biopsy in patients in the expansion cohort)
* 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 negative, a serum pregnancy test will be required. Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
* 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 acceptable if this is the usual lifestyle and preferred contraception for the patient
* 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) 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 imaging \[MRI\] or computed tomography \[CT\] scan, for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy 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
* 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 \[ULN\])
* Measured or calculated creatinine clearance (CrCl) ≥ 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 of anticoagulants
* 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 undergo baseline tumor biopsy in patients in the expansion cohort)
* 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 negative, a serum pregnancy test will be required. Female patients of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient
* 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 acceptable if this is the usual lifestyle and preferred contraception for the patient
* 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) 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 imaging \[MRI\] or computed tomography \[CT\] scan, for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy 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
Exclusion Criteria
* 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 criterion and may qualify for the study. Note: If patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
* 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 of study drug
* 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 arrhythmia that would limit compliance with study requirements
* 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, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* 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 not in the best interest of the patient to participate, in the opinion of the treating investigator
* 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 in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab. These potential risks may also apply to other agents used in this study
* 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)
* 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 of study drug
* 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 arrhythmia that would limit compliance with study requirements
* 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, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
* 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 not in the best interest of the patient to participate, in the opinion of the treating investigator
* 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 in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab. These potential risks may also apply to other agents used in this study
* 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)
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National Cancer Institute (NCI)
NIH
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Matthew D Galsky
Role: PRINCIPAL_INVESTIGATOR
MOUNT SINAI HOSPITAL
Locations
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City of Hope Comprehensive Cancer Center
Duarte, California, United States
Site Status
RECRUITING
UC San Diego Moores Cancer Center
La Jolla, California, United States
Site Status
RECRUITING
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange, California, United States
Site Status
RECRUITING
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, United States
Site Status
RECRUITING
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
Site Status
RECRUITING
Mount Sinai Hospital
New York, New York, United States
Site Status
RECRUITING
NYP/Weill Cornell Medical Center
New York, New York, United States
Site Status
RECRUITING
Countries
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United States
Facility Contacts
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Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Site Public Contact
Role: primary
Other Identifiers
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NCI-2024-04436
Identifier Type: REGISTRY
Identifier Source: secondary_id
10636
Identifier Type: OTHER
Identifier Source: secondary_id
10636
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2024-04436
Identifier Type: -
Identifier Source: org_study_id