Actively Recruiting
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)
Led by Curis, Inc. · Updated on 2026-04-16
152
Participants Needed
45
Research Sites
457 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
This is a multi-center, open-label study to evaluate the safety, pharmacokinetics (PK), and anti-cancer activity of oral administration of emavusertib alone or in combination with ibrutinib in adult participants with relapsed or refractory (R/R) hematologic malignancies. 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.
CONDITIONS
Official Title
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)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Male or female aged 18 years or older
- Life expectancy of at least 3 months
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
- Histopathologically confirmed diagnosis of primary central nervous system lymphoma (PCNSL) or typical imaging consistent with PCNSL
- Participants with parenchymal lesions must have evidence of disease progression with at least one measurable lesion 10 to 40 mm in diameter on brain MRI or head CT within 28 days prior to treatment
- Participants with leptomeningeal involvement require cerebrospinal fluid analysis with or without spinal MRI within 28 days prior to treatment
You will not qualify if you...
- Participants with only intraocular PCNSL without brain lesion or cerebrospinal fluid involvement
- T-cell lymphoma, systemic lymphoma, or non-CNS lymphoma metastatic to the CNS
- Evidence of systemic lymphoma by PET or CT scan at screening
- Prior malignancies other than lymphoma unless disease-free for 3 or more years, except certain skin or cervical/breast carcinomas in situ
- Active malignancy other than PCNSL requiring systemic therapy
- Prior Bruton's tyrosine kinase inhibitor (BTKi) treatment (Part C only)
- History of Grade 3 or higher rhabdomyolysis without full recovery
- Need for urgent therapy due to uncontrolled tumor mass or edema
- External beam radiation therapy to the CNS within 28 days prior to treatment
- Prior investigational drug treatment within 28 days or 5 half-lives before treatment or allogeneic hematopoietic stem cell transplant within 60 days prior
- Clinically significant graft-versus-host disease requiring immunosuppressive medication up-titration prior to screening (except stable or tapering immunosuppression post-transplant)
- Prior systemic anti-cancer treatment within 14 days or 5 half-lives before treatment (except ibrutinib or BTKi for Part B until day before treatment)
- Prior hypersensitivity or anaphylaxis to emavusertib, ibrutinib, or their excipients
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 45 locations
1
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
Actively Recruiting
2
Mayo Clinic
Phoenix, Arizona, United States, 85054
Completed
3
City of Hope
Duarte, California, United States, 91010
Actively Recruiting
4
Providence St. John's Health Center
Santa Monica, California, United States, 90404
Actively Recruiting
5
UCLA Department of Medicine - Hematology/Oncology
Santa Monica, California, United States, 90404
Withdrawn
6
Smilow Cancer Hospital at Yale-New Haven
New Haven, Connecticut, United States, 06510
Completed
7
Mayo Clinic
Jacksonville, Florida, United States, 32224
Actively Recruiting
8
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Actively Recruiting
9
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
10
Mayo Clinic
Rochester, Minnesota, United States, 55905
Actively Recruiting
11
Fred and Pamela Buffett Cancer Center
Omaha, Nebraska, United States, 68198
Actively Recruiting
12
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
Completed
13
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States, 14263
Actively Recruiting
14
Mt Sinai
New York, New York, United States, 10029
Actively Recruiting
15
Columbia University Irving Medical Center
New York, New York, United States, 10032
Withdrawn
16
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
17
Duke University Medical Center, Duke Cancer Center
Durham, North Carolina, United States, 27710
Actively Recruiting
18
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Actively Recruiting
19
Providence Neurological Specialties West
Portland, Oregon, United States, 97225
Actively Recruiting
20
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Completed
21
UPMC Hilman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Actively Recruiting
22
University of Tennessee Medical Center
Knoxville, Tennessee, United States, 37920
Completed
23
UT Southwestern Medical Center
Dallas, Texas, United States, 75235
Active, Not Recruiting
24
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
25
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States, 84112
Actively Recruiting
26
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Completed
27
University of Washington Medical Center
Seattle, Washington, United States, 98195
Actively Recruiting
28
Všeobecná fakultní nemocnice v Praze
Prague, Czechia
Actively Recruiting
29
Institut Bergonie
Bordeaux, France
Actively Recruiting
30
Hopital de la Timone
Marseille, France
Actively Recruiting
31
Hospital Pitie Salpetriere
Paris, France
Actively Recruiting
32
Institut Curie Hospital
Paris, France
Actively Recruiting
33
Hematology Department Soroka UMC / Heanatology Department
Beersheba, Israel
Actively Recruiting
34
Rambam Medical Center
Haifa, Israel
Actively Recruiting
35
Hadassah Medical Center / Ein-Carem
Jerusalem, Israel
Actively Recruiting
36
Università di Torino Croce e Carle
Cuneo, Italy
Actively Recruiting
37
SODc Ematologia Azienda Ospedaliera Universitaria Careggi
Florence, Italy
Actively Recruiting
38
IRST - Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, Italy
Actively Recruiting
39
IRCCS San Raffaele Scientific Institute
Milan, Italy
Actively Recruiting
40
Uniwersyteckie Centrum Kliniczne Osrodek Badan Klinicznych Wczesnych Faz
Gdansk, Poland
Actively Recruiting
41
Oddzial Kliniczny Hematologii
Krakow, Poland
Withdrawn
42
NarodowyInstytutu Onkologii im. Marii Sklodowskiej-Curie-Panstwowy Instytutu Badawczy
Warsaw, Poland
Actively Recruiting
43
University Hospital Vall d'Hebron
Barcelona, Spain
Actively Recruiting
44
MD Anderson Cancer Center Madrid
Madrid, Spain
Actively Recruiting
45
Hospital Universitario Virgen del Rocio
Seville, Spain
Actively Recruiting
Research Team
A
Ahmed Hamdy, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here