NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts.
Deyi Zhang, Hailey M Harris, Jonathan Chen...
https://pubmed.ncbi.nlm.nih.gov/36375120Actively Recruiting
Phase 1
Age: 18Years +
All Genders
ID05131022
A Phase 1, Dose Escalation, and Cohort Expansion Study Evaluating NX-5948, a Bruton's Tyrosine Kinase (BTK) Degrader, in Adults With Relapsed/Refractory B-cell Malignancies
Led by Nurix Therapeutics, Inc. · Updated on 2026-04-14
572
Participants Needed
62
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating NX-5948, a Bruton's tyrosine kinase (BTK) degrader, in adults with relapsed or refractory B-cell malignancies, including several types of lymphoma and leukemia. This first-in-human Phase 1a/1b multicenter, open-label study aims to assess the safety, tolerability, and anti-cancer activity of NX-5948 in patients who have received prior therapies and have limited treatment options. The study includes a Phase 1a dose escalation period to identify the maximum tolerated dose and recommended doses for Phase 1b. Phase 1b Part 1 focuses on safety expansion across up to 17 patient cohorts with specific B-cell malignancies, some involving randomization between two dose levels. Phase 1b Part 2 further investigates anti-tumor activity in one additional cohort of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) patients. NX-5948 is administered orally during these periods. Participants will be closely monitored with assessments including dose-limiting toxicities, treatment-emergent adverse events, and overall response rates evaluated by investigators over several years. Additional measures include pharmacokinetics, pharmacodynamics, complete response rate, duration of response, progression-free survival, and time to next therapy. The study involves regular clinical evaluations, laboratory tests, and follow-up visits lasting up to six years to gather comprehensive safety and effectiveness data.
CONDITIONS
Brief Title
A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Age 60;18 years
- Histologically confirmed relapsed or refractory B-cell malignancy such as CLL, SLL, DLBCL (including subtypes), FL, MCL, MZL (including subtypes), WM, or PCNSL
- For non-PCNSL patients, at least 2 prior lines of therapy with no other therapies providing clinical benefit
- For PCNSL patients, at least 1 prior line of therapy
- Measurable disease according to specific response criteria
- ECOG performance status 0 or 1 (0-2 for PCNSL and secondary CNS involvement)
- Adequate organ and bone marrow function
You will not qualify if you...
- Known or suspected active prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma
- Radiotherapy within 2 weeks before starting study drug (except limited palliative radiation)
- Systemic chemotherapy within 2 weeks before starting study drug
- Monoclonal antibody therapy within 4 weeks before starting study drug (16-week washout for Cohort 16)
- Small molecule therapy within 2 weeks or 5 half-lives before starting study drug
- Stem cell transplant within 100 days before starting study drug
- CAR T-cell therapy within 100 days before starting study drug (60 days for Phase 1b)
- Use of systemic corticosteroids outside allowed dosing within 7 days before treatment
- Use of systemic immunosuppressive drugs other than corticosteroids within 60 days before treatment
- Previous treatment with a BTK degrader
- Active, uncontrolled autoimmune hemolytic anemia or thrombocytopenia (except for Cohort 16)
- Recent history (within 6 months) of serious heart conditions or thromboembolic events
- Bleeding disorders or recent significant bleeding
- Active other malignancies within past 3 years, with some exceptions for certain skin and bladder cancers
AI-Screening
AI-Powered Screening
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 24 months for dose escalation and up to 3 years for cohort expansion
Participants receive oral NX-5948 at various dose levels to evaluate safety, tolerability, and anti-tumor activity. Treatment includes dose escalation and cohort expansion based on prior therapies and specific B-cell malignancy subtypes.
Regular visits throughout treatment duration
Follow-up
Duration - Up to 6 years
Participants are monitored for treatment-emergent adverse events, anti-tumor response, and long-term outcomes after completing treatment.
Visits scheduled periodically post-treatment
Trial Site Locations
Total: 62 locations
1
City of Hope
Duarte, California, United States, 91010
Actively Recruiting
2
University of California, San Francisco
San Francisco, California, United States, 94143
Actively Recruiting
3
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
Actively Recruiting
4
Yale Cancer Center
New Haven, Connecticut, United States, 06510
Actively Recruiting
5
University of Miami
Miami, Florida, United States, 33136
Actively Recruiting
6
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
Actively Recruiting
7
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
Actively Recruiting
8
Northwestern University
Chicago, Illinois, United States, 60611
Actively Recruiting
9
National Institute of Health
Bethesda, Maryland, United States, 20814
Actively Recruiting
10
Cayuga Medical Center
Ithaca, New York, United States, 14850
Withdrawn
11
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Active, Not Recruiting
12
Duke University Medical Center
Durham, North Carolina, United States, 27705
Actively Recruiting
13
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45219
Actively Recruiting
14
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Actively Recruiting
15
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
Actively Recruiting
16
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
17
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Withdrawn
18
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Actively Recruiting
19
CHU Angers
Angers, France, 49933
Actively Recruiting
20
Hôpital Avicenne
Bobigny, France, 93009
Actively Recruiting
21
CHU de Nantes
Nantes, France, 44093
Actively Recruiting
22
CHU Bordeaux
Pessac, France, 33604
Actively Recruiting
23
CHU de Poitiers
Poitiers, France, 86021
Actively Recruiting
24
Institut Curie-Site Saint-Cloud
Saint-Cloud, France, 92210
Actively Recruiting
25
CHRU de Nancy
Vandœuvre-lès-Nancy, France, 54500
Actively Recruiting
26
IRCCS - AOU di Bologna
Bologna, Italy, 40138
Withdrawn
27
ASST Spedali Civili Brescia
Brescia, Italy, 25123
Withdrawn
28
IRCCS Ospedale San Raffaele - Università Vita-Salute San Raffaele di Milano
Milan, Italy, 20132
Actively Recruiting
29
IRCCS Ospedale San Raffaele
Milan, Italy, 20132
Actively Recruiting
30
Fondazione Policlinico Universitario A. Gemelli IRCCS
Rome, Italy, 00168
Actively Recruiting
31
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Withdrawn
32
Radboud University Medical Center
Nijmegen, Netherlands, 6525 GA
Actively Recruiting
33
Erasmus MC
Rotterdam, Netherlands, 3015 GD
Actively Recruiting
34
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Actively Recruiting
35
AidPort sp. Zo.o
Skórzewo, Greater Poland Voivodeship, Poland, 60-185
Actively Recruiting
36
Pratia MCM
Krakow, Lesser Poland Voivodeship, Poland, 30-272
Actively Recruiting
37
University Clinical Hostpital in Wroclaw
Wroclaw, Lower Silesian Voivodeship, Poland, 50-367
Actively Recruiting
38
Pratia MTZ
Warsaw, Masovian Voivodeship, Poland, 02-172
Actively Recruiting
39
National Institute of Oncology Warszawa
Warsaw, Masovian Voivodeship, Poland, 02-781
Actively Recruiting
40
Pratia Onkologia Katowice
Katowice, Silesian Voivodeship, Poland, 40-519
Actively Recruiting
41
Medical University of Lublin
Lublin, Poland, 20-090
Actively Recruiting
42
Hospital Universitari Vall d'Hebron
Barcelona, Spain, 08035
Actively Recruiting
43
Hospital Clínic de Barcelona
Barcelona, Spain, 08036
Actively Recruiting
44
Hospital Universitario de Cabuenes
Gijón, Spain, 33203
Actively Recruiting
45
Hospital Ramón y Cajal
Madrid, Spain, 28034
Actively Recruiting
46
Hospital Fundación Jimenez Díaz - START Madrid
Madrid, Spain, 28040
Actively Recruiting
47
Universitätsspital Basel
Basel, Switzerland, 4031
Actively Recruiting
48
Istituto Oncologico della Svizzera Italiana
Bellinzona, Switzerland
Actively Recruiting
49
Inselspital - Universitatsklinik Bern
Bern, Switzerland, 3010
Actively Recruiting
50
Hôpitaux Universitaires de Genève
Geneva, Switzerland, 1205
Actively Recruiting
51
Kantonsspital St.Gallen
Sankt Gallen, Switzerland, 9007
Actively Recruiting
52
University Hospital Zurich
Zurich, Switzerland, 8091
Actively Recruiting
53
The Beatson WOS Cancer Center
Glasgow, Scotland, United Kingdom, G12 0YN
Actively Recruiting
54
St. James Hospital
Leeds, United Kingdom, LS9 7TF
Actively Recruiting
55
Clatterbridge Cancer Center NHS Foundation Trust
Liverpool, United Kingdom, L7 8YA
Actively Recruiting
56
St. Bartholomew's Hospital, Barts NHS Trust
London, United Kingdom, EC1A 7BE
Actively Recruiting
57
Sarah Cannon Research Institute UK
London, United Kingdom, W1G 6AD
Actively Recruiting
58
The Christie NHS Foundation Trust
Manchester, United Kingdom, M20 4BX
Actively Recruiting
59
Oxford University Hospitals NHS Foundation Trust
Oxford, United Kingdom, OX3 7LE
Actively Recruiting
60
University Hospitals Plymouth NHS Trust
Plymouth, United Kingdom, PL6 8DH
Actively Recruiting
61
University Hospital Southampton NHS Foundation Trust
Southampton, United Kingdom, SO16 6YD
Actively Recruiting
62
Royal Marsden NHS Foundation Trust
Sutton, United Kingdom, SM2 5PT
Actively Recruiting
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Research Team
A
Additional Site Contact Information
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
19
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