Chronic Lymphocytic Leukemia (CLL)Phase 1NCT05131022
A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies
A Phase 1 study testing NX-5948 in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by Nurix Therapeutics, Inc. at 62 sites in 8 countries.
Trial summary
This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Diffuse Large B Cell Lymphoma (DLBCL)
- What is being tested?
- NX-5948
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 572 participants
- Where
- 62 sitesin 8 countries
- Study dates
- 13 Apr 2022to Jan 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, DLBCL (subgroups include Richter-transformed DLBCL, germinal center B-cell type, activated B-cell type, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS), FL, MCL, MZL (subtypes include EMZL, MALT, NMZL, SMZL), WM, or PCNSL.
- Patients in Phase 1a must meet the following:
- o For non-PCNSL indications, received at least 2 prior lines of therapy and have no other available therapies known to provide clinical benefit. For PCNSL, received at least 1 prior line of therapy
- Patients in Phase 1b (Safety and Cohort Expansion) must have 1 of the following histologically documented B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies and/or molecular features based on details described for each cohort: CLL or SLL, DLBCL, MCL, FL, MZL, WM, or PCNSL/SCNSL.
- Measurable disease per response criteria specific to the malignancy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0-2 for patients with PCNSL and secondary CNS involvement).
- Adequate organ and bone marrow function
Who cannot join
- Known or suspected active prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma prior to study enrollment
- Prior treatment for the indication under study for anti-cancer intent that includes:
- Radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation).
- Prior systemic chemotherapy within 2 weeks of planned start of study drug.
- Prior monoclonal antibody therapy within 4 weeks of planned start of study drug, except for patients enrolling in Cohort 16 (CLL with secondary wAIHA) where a 16-week washout period is required.
- Prior small molecule therapy within 2 weeks or 5 half-lives (whichever is shorter) of planned start of study drug.
Show all 20Show fewer
- Autologous or allogeneic stem cell transplant within 100 days prior to planned start of study drug.
- Chimeric antigen receptor (CAR) T-cell therapy within 100 days prior to start of study drug (within 60 days prior to start of study drug for Phase 1b).
- Use of systemic corticosteroids outside of dosing limits described below and within 7 days prior to initiation of study treatment excepting those used as prophylaxis for radio diagnostic contrast. Patients with PCNSL/SCNSL: no greater than 40 mg/day prednisone, or equivalent. Patients with PCNSL/SCNSL using greater than 20 mg/day prednisone, or equivalent, must be clinically stable at that dose for 7 days. All other diagnoses: no greater than 20 mg/day prednisone or equivalent.
- Use of systemic immunosuppressive drugs other than systemic corticosteroids for any medical condition within 60 days prior to first dose of study drug
- Previously treated with a BTK degrader
- Active, uncontrolled autoimmune hemolytic anemia (except for patients enrolling in Cohort 16) or active, uncontrolled autoimmune thrombocytopenia.
- Patient has any of the following within 6 months of planned start of study drug:
- Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, or placement of a coronary arterial stent
- Uncontrolled atrial fibrillation or other clinically significant arrhythmias, conduction abnormalities, or New York Heart Association (NYHA) class III or IV heart failure
- Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage
- Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, severe congenital heart disease, or persistent uncontrolled hypertension defined as systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg despite optimal medical management)
- Bleeding diathesis, or other known risk for acute blood loss.
- History of Grade ≥ 2 hemorrhage within 28 days of planned start of study drug.
- Active known concurrent malignancy or malignancy other than the one under study within the past 3 years. (Exceptions include, but are not limited to, patients with more recent history of basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast may enroll if they have undergone curative therapy and have no evidence of disease).
Trial locations and contacts
62 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
62 sites in 8 countries
United States18 sites, 15 recruiting
- Recruiting
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
- Recruiting
National Institute of Health
Bethesda, Maryland, 20814
- Recruiting
Northwestern University
Chicago, Illinois, 60611
- Recruiting
University of Cincinnati Medical Center
Cincinnati, Ohio, 45219
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
- Recruiting
Colorado Blood Cancer Institute
Denver, Colorado, 80218
- Recruiting
City of Hope
Duarte, California, 91010
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27705
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Ana Ayala, 713-792-4254, abayala@mdanderson.org
- Withdrawn
Cayuga Medical Center
Ithaca, New York, 14850
- Recruiting
University of Miami
Miami, Florida, 33136
- Recruiting
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
- Recruiting
Yale Cancer Center
New Haven, Connecticut, 06510
- Active, not recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
- Withdrawn
Huntsman Cancer Institute
Salt Lake City, Utah, 84112
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
HDFCCCClinicalTrials@ucsf.edu
- Recruiting
Florida Cancer Specialists
Sarasota, Florida, 34232
United Kingdom10 sites, 10 recruiting
- Recruiting
The Beatson WOS Cancer Center
Glasgow, Scotland, G12 0YN
- Recruiting
St. James Hospital
Leeds, LS9 7TF
- Recruiting
Clatterbridge Cancer Center NHS Foundation Trust
Liverpool, L7 8YA
- Recruiting
St. Bartholomew's Hospital, Barts NHS Trust
London, EC1A 7BE
- Recruiting
Sarah Cannon Research Institute UK
London, W1G 6AD
- Recruiting
The Christie NHS Foundation Trust
Manchester, Manchester, M20 4BX
- Recruiting
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 7LE
- Recruiting
University Hospitals Plymouth NHS Trust
Plymouth, PL6 8DH
- Recruiting
University Hospital Southampton NHS Foundation Trust
Southampton, SO16 6YD
- Recruiting
Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
France7 sites, 7 recruiting
- Recruiting
CHU Angers
Angers, 49933
- Recruiting
Hôpital Avicenne
Bobigny, 93009
- Recruiting
CHU de Nantes
Nantes, 44093
- Recruiting
CHU Bordeaux
Pessac, 33604
- Recruiting
CHU de Poitiers
Poitiers, 86021
- Recruiting
Institut Curie-Site Saint-Cloud
Saint-Cloud, 92210
- Recruiting
CHRU de Nancy
Vandœuvre-lès-Nancy, 54500
Poland7 sites, 7 recruiting
- Recruiting
Pratia Onkologia Katowice
Katowice, Silesian Voivodeship, 40-519
- Recruiting
Pratia MCM
Krakow, Lesser Poland Voivodeship, 30-272
- Recruiting
Medical University of Lublin
Lublin, 20-090
- Recruiting
AidPort sp. Zo.o
Skórzewo, Greater Poland Voivodeship, 60-185
- Recruiting
Pratia MTZ
Warsaw, Masovian Voivodeship, 02-172
- Recruiting
National Institute of Oncology Warszawa
Warsaw, Masovian Voivodeship, 02-781
- Recruiting
University Clinical Hostpital in Wroclaw
Wroclaw, Lower Silesian Voivodeship, 50-367
Switzerland6 sites, 3 recruiting
- Recruiting
Universitätsspital Basel
Basel, 4031
- Recruiting
Istituto Oncologico della Svizzera Italiana
Bellinzona
- Withdrawn
Inselspital - Universitatsklinik Bern
Bern, 3010
- Withdrawn
Hôpitaux Universitaires de Genève
Geneva, 1205
- Withdrawn
Kantonsspital St.Gallen
Sankt Gallen, 9007
- Recruiting
University Hospital Zurich
Zurich, 8091
Italy5 sites, 3 recruiting
- Withdrawn
IRCCS - AOU di Bologna
Bologna, 40138
- Withdrawn
ASST Spedali Civili Brescia
Brescia, 25123
- Recruiting
IRCCS Ospedale San Raffaele - Università Vita-Salute San Raffaele di Milano
Milan, 20132
- Recruiting
IRCCS Ospedale San Raffaele
Milan, 20132
- Recruiting
Fondazione Policlinico Universitario A. Gemelli IRCCS
Rome, 00168
Spain5 sites, 5 recruiting
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
- Recruiting
Hospital Clínic de Barcelona
Barcelona, 08036
- Recruiting
Hospital Universitario de Cabuenes
Gijón, 33203
- Recruiting
Hospital Ramón y Cajal
Madrid, 28034
- Recruiting
Hospital Fundación Jimenez Díaz - START Madrid
Madrid, 28040
Netherlands4 sites, 3 recruiting
- Withdrawn
University Medical Center Groningen
Groningen, 9713 GZ
- Recruiting
Radboud University Medical Center
Nijmegen, 6525 GA
- Recruiting
Erasmus MC
Rotterdam, 3015 GD
- Recruiting
University Medical Center Utrecht
Utrecht, 3584 CX
About this study
Official title: 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
This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.
Read the detailed description
Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) B cell malignancies who have received at least 2 prior lines of therapy, or at least 1 prior line of therapy for Primary Central Nervous System Lymphoma (PCNSL), and for whom no other therapies are known to provide clinical benefit. Indications include: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Diffuse Large B-cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL), Waldenstrom Macroglobulinemia (WM), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL), Primary Central Nervous System Lymphoma (PCNSL) or any of the above indications with disease in the central nervous system or Secondary Central Nervous System Lymphoma (SCNSL).
Phase 1b Part 1, called safety expansion, investigates the safety and anti-tumor activity of NX-5948 at the dose(s) selected in Phase 1a in up to 17 expansion cohorts of patients with histologically confirmed B-cell malignancy indications who have received specified prior therapies based on indication:
- CLL or SLL (patients may be randomized to one of two dose levels investigated for CLL/SLL until an optimal dose is selected)
- MCL
- MZL
- WM
- DLBCL
- FL
- PCNSL/SCNSL
Phase 1b Part 2, called cohort expansion, will further investigate the anti-tumor activity of NX-5948 at the dose(s) selected in Phase 1b par 1 in one additional expansion arm of CLL/SLL patients.
- Conditions
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL)
- Being tested
- NX-5948
- Keywords
- BTK Degrader, BTK Inhibitor, B-Cell Malignancy, Lymphoma, C481, C481S, Bruton's Tyrosine Kinase, NX-5948, Targeted Protein Degradation, Chimeric Targeting Molecule (CTM)
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Waldenstrom Macroglobulinemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NX-5948Drug
Oral NX-5948
| Study group | Role | What they receive |
|---|---|---|
| Phase 1a Dose Escalation | Experimental | Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose(s) Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 1 in CLL or SLL with prior BTKi and BCL2i | Experimental | CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor, unless previously deemed ineligible for a BCL-2i. Patients enrolled in CLL/SLL arm will be randomized to one of two dose levels. Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 2 in CLL/SLL with non-C481S BTK mutations | Experimental | Prior exposure to both BTKi and BCL-2i (unless deemed ineligible for BCL-2i by Investigator at the time of study enrollment) and documented BTK mutation other than C481S within 6 months prior to study entry Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 3 in CLL/SLL with prior non-covalent BTKi | Experimental | CLL/SLL with prior exposure to ncBTKi and are BCL-2i naïve. Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 4 in CLL/SLL with TP53 or 17p deletion, 2L, prior BTKi | Experimental | Patients with documented TP53 mutation or 17p deletion and 1 prior line of therapy that included a BTKi and are BCL-2i naïve. Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 5 in CLL/SLL with 2L+, prior BTKi | Experimental | Patients with at least 1 prior line of therapy that included a BTKi and are BCL-2i naïve. Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 6 in MCL | Experimental | Non-blastoid MCL with prior exposure to a BTKi and an anti-CD20 monoclonal antibody (mAb)-based chemoimmunotherapy regimen Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 7 in MZL | Experimental | MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and an additional line of therapy Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 8 in WM (3L+) | Experimental | WM with prior exposure to a BTKi and at least an additional line of therapy Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 9 in WM (2L) | Experimental | WM following upfront therapy with a BTKi Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 10 in DLBCL | Experimental | DLBCL which transformed from indolent lymphoma or Richters transformation with prior exposure to an anthracycline (unless previously deemed ineligible to receive), an anti-CD20 mAb-based chemoimmunotherapy regimen, and an additional line of therapy Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 11 in FL | Experimental | FL (grade 1-3a) with prior exposure to an anti-CD20 mAb-based chemoimmunotherapy regimen and an additional line of therapy Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 12 in PCNSL/SCNSL | Experimental | PCNSL following at least 1 prior line of therapy that included a BTKi (2L+) or following 2 or more prior lines of therapy (3L+), or SCNSL patients meeting criteria for a non-CLL/SLL cohort enrolling that disease with secondary CNS involvement of lymphoma Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 13 in PCNSL | Experimental | PCNSL following upfront therapy and with no prior exposure to a BTKi (2L). Receives: Drug: NX-5948 |
| Phase 1b Part 2 in CLL or SLL with prior BTKi and BCL-2i | Experimental | CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 14 in first-line WM | Experimental | Treatment-naïve WM deemed unfit for chemoimmunotherapy Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 15 in BTKi-naive CLL/SLL | Experimental | First-line (1L) or second-line+ (2L)+ CLL/SLL with no prior exposure to a BTKi Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 16 in CLL/SLL with secondary warm autoimmune hemolytic anemia (wAIHA) | Experimental | BTKi-exposed R/R CLL or SLL with secondary wAIHA Receives: Drug: NX-5948 |
| Phase 1b Part 1 Cohort 17 in CLL/SLL with CNS involvement | Experimental | BTKi-exposed R/R CLL or SLL with CNS involvement Receives: Drug: NX-5948 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with protocol specified dose-limiting toxicities
Phase 1a
Measured: Up to 24 months
To establish the maximum tolerated dose and/or recommended Phase 1b dose(s)
Phase 1a
Measured: Up to 24 months
To evaluate the anti-tumor activity of NX-5948 in the dose levels selected for Phase 1b safety expansion based on overall response rate (ORR) as assessed by Investigator
Phase 1b Part 1
Measured: Up to 3 years
Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths
Phase 1a / Phase 1b Part 1
Measured: Up to 6 years
To further evaluate the anti-tumor activity of NX-5948 in patients with CLL/SLL at the dose identified in Phase 1b Part 1 based on overall response rate (ORR) as assessed by Investigator
Phase 1b Part 2
Measured: Up to 3 years
Secondary outcomes (7)
Pharmacokinetic (PK) profile of NX-5948: Maximum Serum Concentration
Phase 1a / Phase 1b Part 1 and Part 2 - Sampling following the first dose, pre- and post-dose at selected cycles and at the end of treatment
Measured: Up to 6 years
Pharmacodynamic (PD) profile of NX-5948: Changes from baseline of BTK levels in B-cells
Phase 1a / Phase 1b Part 1 and Part 2 - Sampling at screening, following the first dose, pre and post-dose at selected cycles and at the end of treatment
Measured: Up to 6 years
Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator
Phase 1a / Phase 1b Part 1 and Part 2
Measured: Up to 6 years
Duration of response (DOR) as assessed by the Investigator
Phase 1a / Phase 1b Part 1 and Part 2
Measured: Up to 6 years
Progression-free survival (PFS) as assessed by the Investigator
Phase 1a / Phase 1b Part 1 and Part 2
Measured: Up to 6 years
Time to next therapy
Phase 1a / Phase 1b Part 1 and Part 2
Measured: Up to 6 years
Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths
Phase 1b Part 2
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2021
- Study start13 Apr 2022
- Primary completionJan 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic Leukemia (CLL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 572 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nurix Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Nurix Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05131022
- Sponsor's protocol ID
- NX-5948-301
- Other IDs
- 2023-510541-25-00, 2021-003125-29, 2023
- Status last verified
- Jun 2026
- First submitted
- 12 Nov 2021
- Last updated
- 2 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhang D, Harris HM, Chen J, Judy J, James G, Kelly A, McIntosh J, Tenn-McClellan A, Ambing E, Tan YS, Lu H, Gajewski S, Clifton MC, Yung S, Robbins DW, Pirooznia M, Skanland SS, Gaglione E, Mhibik M, Underbayev C, Ahn IE, Sun C, Herman SEM, Noviski M, Wiestner A. NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts. Blood. 2023 Mar 30;141(13):1584-1596. doi: 10.1182/blood.2022016934.
PubMed 36375120
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05131022
- Acronym / sponsor ID
- NX-5948-301
- Conditions
- Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL)
- Keywords
- BTK Degrader, BTK Inhibitor, B-Cell Malignancy, Lymphoma, C481, C481S, Bruton's Tyrosine Kinase, NX-5948
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 572 participants (estimated)
- Lead sponsor
- Nurix Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Apr 2022 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 23 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.
Detailed description
Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) B cell malignancies who have received at least 2 prior lines of therapy, or at least 1 prior line of therapy for Primary Central Nervous System Lymphoma (PCNSL), and for whom no other therapies are known to provide clinical benefit. Indications include: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Diffuse Large B-cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL), Waldenstrom Macroglobulinemia (WM), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL), Primary Central Nervous System Lymphoma (PCNSL) or any of the above indications with disease in the central nervous system or Secondary Central Nervous System Lymphoma (SCNSL).
Phase 1b Part 1, called safety expansion, investigates the safety and anti-tumor activity of NX-5948 at the dose(s) selected in Phase 1a in up to 17 expansion cohorts of patients with histologically confirmed B-cell malignancy indications who have received specified prior therapies based on indication:
- CLL or SLL (patients may be randomized to one of two dose levels investigated for CLL/SLL until an optimal dose is selected)
- MCL
- MZL
- WM
- DLBCL
- FL
- PCNSL/SCNSL
Phase 1b Part 2, called cohort expansion, will further investigate the anti-tumor activity of NX-5948 at the dose(s) selected in Phase 1b par 1 in one additional expansion arm of CLL/SLL patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 19
| Arm | Type | Receives |
|---|---|---|
| Phase 1a Dose Escalation | Experimental | Drug: NX-5948Multiple dose levels of NX-5948 to be evaluated; determination of Maximum Tolerated Dose/Phase 1b recommended dose(s) |
| Phase 1b Part 1 Cohort 1 in CLL or SLL with prior BTKi and BCL2i | Experimental | Drug: NX-5948CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor, unless previously deemed ineligible for a BCL-2i. Patients enrolled in CLL/SLL arm will be randomized to one of two dose levels. |
| Phase 1b Part 1 Cohort 2 in CLL/SLL with non-C481S BTK mutations | Experimental | Drug: NX-5948Prior exposure to both BTKi and BCL-2i (unless deemed ineligible for BCL-2i by Investigator at the time of study enrollment) and documented BTK mutation other than C481S within 6 months prior to study entry |
| Phase 1b Part 1 Cohort 3 in CLL/SLL with prior non-covalent BTKi | Experimental | Drug: NX-5948CLL/SLL with prior exposure to ncBTKi and are BCL-2i naïve. |
| Phase 1b Part 1 Cohort 4 in CLL/SLL with TP53 or 17p deletion, 2L, prior BTKi | Experimental | Drug: NX-5948Patients with documented TP53 mutation or 17p deletion and 1 prior line of therapy that included a BTKi and are BCL-2i naïve. |
| Phase 1b Part 1 Cohort 5 in CLL/SLL with 2L+, prior BTKi | Experimental | Drug: NX-5948Patients with at least 1 prior line of therapy that included a BTKi and are BCL-2i naïve. |
| Phase 1b Part 1 Cohort 6 in MCL | Experimental | Drug: NX-5948Non-blastoid MCL with prior exposure to a BTKi and an anti-CD20 monoclonal antibody (mAb)-based chemoimmunotherapy regimen |
| Phase 1b Part 1 Cohort 7 in MZL | Experimental | Drug: NX-5948MZL (EMZL, MALT, NMZL, SMZL) with prior exposure to an anti-CD20 mAb-based chemo-immunotherapy regimen and an additional line of therapy |
| Phase 1b Part 1 Cohort 8 in WM (3L+) | Experimental | Drug: NX-5948WM with prior exposure to a BTKi and at least an additional line of therapy |
| Phase 1b Part 1 Cohort 9 in WM (2L) | Experimental | Drug: NX-5948WM following upfront therapy with a BTKi |
| Phase 1b Part 1 Cohort 10 in DLBCL | Experimental | Drug: NX-5948DLBCL which transformed from indolent lymphoma or Richters transformation with prior exposure to an anthracycline (unless previously deemed ineligible to receive), an anti-CD20 mAb-based chemoimmunotherapy regimen, and an additional line of therapy |
| Phase 1b Part 1 Cohort 11 in FL | Experimental | Drug: NX-5948FL (grade 1-3a) with prior exposure to an anti-CD20 mAb-based chemoimmunotherapy regimen and an additional line of therapy |
| Phase 1b Part 1 Cohort 12 in PCNSL/SCNSL | Experimental | Drug: NX-5948PCNSL following at least 1 prior line of therapy that included a BTKi (2L+) or following 2 or more prior lines of therapy (3L+), or SCNSL patients meeting criteria for a non-CLL/SLL cohort enrolling that disease with secondary CNS involvement of lymphoma |
| Phase 1b Part 1 Cohort 13 in PCNSL | Experimental | Drug: NX-5948PCNSL following upfront therapy and with no prior exposure to a BTKi (2L). |
| Phase 1b Part 2 in CLL or SLL with prior BTKi and BCL-2i | Experimental | Drug: NX-5948CLL or SLL with prior exposure to both a Bruton's tyrosine kinase inhibitor (BTKi) and BCL-2 inhibitor |
| Phase 1b Part 1 Cohort 14 in first-line WM | Experimental | Drug: NX-5948Treatment-naïve WM deemed unfit for chemoimmunotherapy |
| Phase 1b Part 1 Cohort 15 in BTKi-naive CLL/SLL | Experimental | Drug: NX-5948First-line (1L) or second-line+ (2L)+ CLL/SLL with no prior exposure to a BTKi |
| Phase 1b Part 1 Cohort 16 in CLL/SLL with secondary warm autoimmune hemolytic anemia (wAIHA) | Experimental | Drug: NX-5948BTKi-exposed R/R CLL or SLL with secondary wAIHA |
| Phase 1b Part 1 Cohort 17 in CLL/SLL with CNS involvement | Experimental | Drug: NX-5948BTKi-exposed R/R CLL or SLL with CNS involvement |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age ≥18 years
- Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, DLBCL (subgroups include Richter-transformed DLBCL, germinal center B-cell type, activated B-cell type, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS), FL, MCL, MZL (subtypes include EMZL, MALT, NMZL, SMZL), WM, or PCNSL.
- Patients in Phase 1a must meet the following:
- o For non-PCNSL indications, received at least 2 prior lines of therapy and have no other available therapies known to provide clinical benefit. For PCNSL, received at least 1 prior line of therapy
- Patients in Phase 1b (Safety and Cohort Expansion) must have 1 of the following histologically documented B-cell malignancies, must meet criteria for systemic treatment, and must have received prior therapies and/or molecular features based on details described for each cohort: CLL or SLL, DLBCL, MCL, FL, MZL, WM, or PCNSL/SCNSL.
Key exclusion criteria (20 listed)
- Known or suspected active prolymphocytic leukemia or Richter's transformation to Hodgkin's lymphoma prior to study enrollment
- Prior treatment for the indication under study for anti-cancer intent that includes:
- Active, uncontrolled autoimmune hemolytic anemia (except for patients enrolling in Cohort 16) or active, uncontrolled autoimmune thrombocytopenia.
- Patient has any of the following within 6 months of planned start of study drug:
- Bleeding diathesis, or other known risk for acute blood loss.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NX-5948Oral NX-5948 | Drug | Phase 1a Dose Escalation, Phase 1b Part 1 Cohort 1 in CLL or SLL with prior BTKi and BCL2i, Phase 1b Part 1 Cohort 10 in DLBCL, Phase 1b Part 1 Cohort 11 in FL, Phase 1b Part 1 Cohort 12 in PCNSL/SCNSL, Phase 1b Part 1 Cohort 13 in PCNSL, Phase 1b Part 1 Cohort 14 in first-line WM, Phase 1b Part 1 Cohort 15 in BTKi-naive CLL/SLL, Phase 1b Part 1 Cohort 16 in CLL/SLL with secondary warm autoimmune hemolytic anemia (wAIHA), Phase 1b Part 1 Cohort 17 in CLL/SLL with CNS involvement, Phase 1b Part 1 Cohort 2 in CLL/SLL with non-C481S BTK mutations, Phase 1b Part 1 Cohort 3 in CLL/SLL with prior non-covalent BTKi, Phase 1b Part 1 Cohort 4 in CLL/SLL with TP53 or 17p deletion, 2L, prior BTKi, Phase 1b Part 1 Cohort 5 in CLL/SLL with 2L+, prior BTKi, Phase 1b Part 1 Cohort 6 in MCL, Phase 1b Part 1 Cohort 7 in MZL, Phase 1b Part 1 Cohort 8 in WM (3L+), Phase 1b Part 1 Cohort 9 in WM (2L), Phase 1b Part 2 in CLL or SLL with prior BTKi and BCL-2i |
Primary outcome
Number of participants with protocol specified dose-limiting toxicities
Time frame: Up to 24 months
Phase 1a
To establish the maximum tolerated dose and/or recommended Phase 1b dose(s)
Time frame: Up to 24 months
Phase 1a
To evaluate the anti-tumor activity of NX-5948 in the dose levels selected for Phase 1b safety expansion based on overall response rate (ORR) as assessed by Investigator
Time frame: Up to 3 years
Phase 1b Part 1
Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths
Time frame: Up to 6 years
Phase 1a / Phase 1b Part 1
To further evaluate the anti-tumor activity of NX-5948 in patients with CLL/SLL at the dose identified in Phase 1b Part 1 based on overall response rate (ORR) as assessed by Investigator
Time frame: Up to 3 years
Phase 1b Part 2
7 secondary outcomes
Pharmacokinetic (PK) profile of NX-5948: Maximum Serum Concentration
Time frame: Up to 6 years
Pharmacodynamic (PD) profile of NX-5948: Changes from baseline of BTK levels in B-cells
Time frame: Up to 6 years
Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator
Time frame: Up to 6 years
Duration of response (DOR) as assessed by the Investigator
Time frame: Up to 6 years
Progression-free survival (PFS) as assessed by the Investigator
Time frame: Up to 6 years
Time to next therapy
Time frame: Up to 6 years
Number of participants with treatment-emergent adverse events (TEAEs); Grade 3, 4, 5 TEAEs, serious adverse events (SAEs), TEAEs leading to study drug discontinuation, deaths due to TEAEs, and all deaths
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2026.
- Derived from this study: PubMed 36375120Zhang D, Harris HM, Chen J, Judy J, James G, Kelly A, McIntosh J, Tenn-McClellan A, Ambing E, Tan YS, Lu H, Gajewski S, Clifton MC, Yung S, Robbins DW, Pirooznia M, Skanland SS, Gaglione E, Mhibik M, Underbayev C, Ahn IE, Sun C, Herman SEM, Noviski M, Wiestner A. NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts. Blood. 2023 Mar 30;141(13):1584-1596. doi: 10.1182/blood.2022016934.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Study Director study director
Nurix Therapeutics, Inc.
62 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing NX-5948 in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by Nurix Therapeutics, Inc. at 62 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 62 sites in United States, United Kingdom, France, Poland, Switzerland and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Additional Site Contact Information (+1 (415) 417-3418, clinicaltrials@nurixtx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with protocol specified dose-limiting toxicities (time frame: Up to 24 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05131022, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2026.