CA-4948-101: Open-Label, Dose Escalation and Expansion Trial of Emavusertib (CA-4948) in Relapsed or Refractory Primary Central Nervous System Lymphoma (R/R PCNSL)
NCT ID: NCT03328078
Last Updated: 2025-06-05
Study Results
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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RECRUITING
PHASE1/PHASE2
152 participants
INTERVENTIONAL
2017-12-28
2026-10-31
Brief Summary
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This trial will be completed in four parts. In Part A1, emavusertib will be evaluated first in a dose escalating monotherapy setting to establish the safety and tolerability (complete). In Part A2, emavusertib will be evaluated in combination with ibrutinib at 560 milligrams (mg) once daily (QD) or 420 mg QD as indicated by disease (Part A2 complete).
Part B will comprise 2 cohorts to assess safety and efficacy of emavusertib in combination with ibrutinib in participants with R/R primary central nervous system lymphoma (PCNSL) who have directly progressed on a bruton tyrosine kinase inhibitor (BTKi). In this part of the study, emavusertib will be dosed at 100 mg or 200 mg twice daily (BID) in combination with ibrutinib in 28-day treatment cycles.
Part C will comprise 3 treatment arms in the second-line setting to assess the efficacy and safety of emavusertib monotherapy, ibrutinib monotherapy, and emavusertib in combination with ibrutinib in participants with R/R PCNSL who are naïve to BTKi treatment. In this part of the study, eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will be randomized 1:1:1 to 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD.
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Emavusertib (CA-4948) dose escalation
Part A1: Dose-level cohorts with up to approximately 6 participants each will be used to define the Maximum Tolerated Dose (MTD) for emavusertib.
Emavusertib
Emavusertib will be provided as a tablet dosage form to be taken BID.
Emavusertib (CA-4948) and ibrutinib dose escalation
Part A2: Evaluate escalating dose levels of oral emavusertib in combination with 560 mg QD or 420 mg QD of oral ibrutinib. The starting dose of emavusertib to be used in combination will be 200 mg BID. It is anticipated that 12 to 20 participants at a potential dose level will be required to establish optimal combination dosing.
Emavusertib
Emavusertib will be provided as a tablet dosage form to be taken BID.
Ibrutinib
Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Emavusertib (CA-4948) and ibrutinib dose expansion
In two Expansion Cohorts (Part B), emavusertib in combination with ibrutinib will be administered in participants with R/R PCNSL who have progressed on a BTKi. In Cohort 1, emavusertib 100 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles. In Cohort 2, emavusertib 200 mg BID will be administered with ibrutinib 560 mg QD consecutively in 28-day treatment cycles.
Emavusertib
Emavusertib will be provided as a tablet dosage form to be taken BID.
Ibrutinib
Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Emavusertib (CA-4948) and ibrutinib
In this part of the study (Part C), eligible second-line participants with R/R PCNSL who are naïve to BTKi treatment will receive 1 of 3 treatment arms: (1) emavusertib 200 mg BID, (2) ibrutinib 560 mg QD, or (3) emavusertib 200 mg BID in combination with ibrutinib 560 mg QD. Treatments will be administered continuously in 28-day treatment cycles.
Emavusertib
Emavusertib will be provided as a tablet dosage form to be taken BID.
Ibrutinib
Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Interventions
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Emavusertib
Emavusertib will be provided as a tablet dosage form to be taken BID.
Ibrutinib
Ibrutinib will be provided as a tablet or capsule dosage form to be taken QD.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Life expectancy of at least 3 months
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2
4. Histopathologically confirmed diagnosis of PCNSL (medical record is acceptable). Cerebral biopsies are not required if imaging reveals typical images of PCNSL.
1. Participants with parenchymal lesions must have unequivocal evidence of disease progression (e.g., presence of at least 1 measurable target lesion \[≥ 10 millimeters (mm) and ≤ 40 mm in the longest diameter on brain magnetic resonance imaging \[MRI\] or head computed tomography \[CT\] on imaging within 28 days prior to Cycle 1 Day 1\]). In cases where the tumor size is smaller but still measurable and located at a critical central nervous system (CNS) location, disabling the participant and/or causing symptoms, this participant may be eligible following a discussion with the Sponsor Medical Monitor.
2. For participants limited to leptomeningeal involvement, cerebrospinal fluid (CSF) analysis (cytology and/or flow cytometry) with or without additional imaging (MRI) of the spine as clinically indicated is required to document abnormal cells within 28 days prior to Cycle 1 Day 1.
Exclusion Criteria
2. Evidence of systemic lymphoma. This must be demonstrated by a positron emission tomography (PET) scan (or CT scan with contrast if applicable) of the chest, abdomen, and pelvis at Screening (testicular ultrasound may be considered to exclude a testicular lymphoma disseminated to the brain).
3. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) or prior history of systemic lymphoma, unless the participant has been free of the disease for ≥ 3 years.
4. Active malignancy other than PCNSL requiring systemic therapy
5. Previous BTKi treatment (Part C only).
6. History of Grade ≥ 3 rhabdomyolysis without complete recovery
7. Requirement for urgent therapy due to uncontrolled tumor mass/edema effects.
8. Received external beam radiation therapy to the CNS within 28 days prior to Cycle 1 Day 1.
9. Received prior investigational drugs (including treatment in clinical research, unapproved combination products, and new dosage forms) within 28 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1; allogeneic hematopoietic stem cell transplant (HSCT) within 60 days prior to Cycle 1 Day 1; or had clinically significant graft-versus-host disease (GVHD) requiring ongoing up-titration of immunosuppressive medications prior to Screening (with the exception of a BTKi for Part B only).
Note: The use of a stable or tapering dose of immunosuppressive therapy post-HSCT and/or topical steroids for ongoing skin GVHD is permitted with Sponsor Medical Monitor approval
10. Any prior systemic anti-cancer treatment such as chemotherapy, immunomodulatory drug therapy, etc., received within 14 days or 5 half-lives, whichever is shorter, prior to Cycle 1 Day 1 (with the exception of ibrutinib or other BTKi for Part B only, which may be continued until the day before Cycle 1 Day 1)
11. Prior history of hypersensitivity or anaphylaxis to emavusertib, ibrutinib or any of their excipients.
18 Years
ALL
No
Sponsors
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Curis, Inc.
INDUSTRY
Responsible Party
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Locations
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St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States
Mayo Clinic
Phoenix, Arizona, United States
City of Hope
Duarte, California, United States
Providence St. John's Health Center
Santa Monica, California, United States
UCLA Department of Medicine - Hematology/Oncology
Santa Monica, California, United States
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, United States
Mayo Clinic
Jacksonville, Florida, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Fred and Pamela Buffett Cancer Center
Omaha, Nebraska, United States
Hackensack University Medical Center
Hackensack, New Jersey, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
Mt Sinai
New York, New York, United States
Columbia University Irving Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Duke University Medical Center, Duke Cancer Center
Durham, North Carolina, United States
Cleveland Clinic
Cleveland, Ohio, United States
Providence Neurological Specialties West
Portland, Oregon, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
UPMC Hilman Cancer Center
Pittsburgh, Pennsylvania, United States
University of Tennessee Medical Center
Knoxville, Tennessee, United States
UT Southwestern Medical Center
Dallas, Texas, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States
Swedish Cancer Institute
Seattle, Washington, United States
University of Washington Medical Center
Seattle, Washington, United States
Všeobecná fakultní nemocnice v Praze
Prague, , Czechia
Institut Bergonie
Bordeaux, , France
Hopital de la Timone
Marseille, , France
Hospital Pitie Salpetriere
Paris, , France
Institut Curie Hospital
Paris, , France
Hematology Department Soroka UMC / Heanatology Department
Beersheba, , Israel
Hadassah Medical Center / Ein-Carem
Jerusalem, , Israel
Università di Torino Croce e Carle
Cuneo, , Italy
SODc Ematologia Azienda Ospedaliera Universitaria Careggi
Florence, , Italy
IRST - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, , Italy
IRCCS San Raffaele Scientific Institute
Milan, , Italy
Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
Gdansk, , Poland
Oddzial Kliniczny Hematologii
Krakow, , Poland
NarodowyInstytutu Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytutu Badawczy
Warsaw, , Poland
MD Anderson Cancer Center Madrid
Madrid, , Spain
Hospital Universitario Virgen del Rocio
Seville, , Spain
Countries
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Central Contacts
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Other Identifiers
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2024-513312-95-00
Identifier Type: CTIS
Identifier Source: secondary_id
2022-000891-20
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
CA-4948-101
Identifier Type: -
Identifier Source: org_study_id
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