ClinicalTrials.gov record NCT05131022
A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies
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
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This first-in-human Phase 1 trial studies oral NX-5948 in adults with relapsed or refractory B-cell malignancies. It begins with dose escalation to find tolerated dose(s) and then opens multiple disease-specific expansion cohorts. The study is open-label and evaluates safety, side effects, and anti-tumor activity.
What it is studying. The study is testing oral NX-5948 to determine safe dose levels, to characterize its side-effect profile and how the drug behaves in the body, and to assess anti-tumor activity across several B-cell malignancy types.
What the researchers hope to learn. Scientific goals are to establish maximum tolerated dose and/or recommended Phase 1b dose(s); record treatment-emergent adverse events and serious adverse events; evaluate anti-tumor activity (overall response rate, complete response rate, duration of response, progression-free survival); and describe pharmacokinetic and pharmacodynamic effects including changes in BTK levels.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- NX-5948
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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
- Key
Exclusion criteria
- 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.
- 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).
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
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.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants receive oral NX-5948 as part of a Phase 1 dose-escalation or cohort-expansion treatment plan. You will attend regular clinic visits for safety checks and assessments of cancer response; some CLL/SLL participants may be randomized to one of two dose levels. Blood samples will be collected at screening, after the first dose, before and after dosing at selected cycles, and at the end of treatment to measure drug levels (pharmacokinetics) and BTK levels in B-cells (pharmacodynamics). The study team will record side effects and response outcomes over the follow-up period described in the protocol.
How the study is structured. Open-label Phase 1 study with a dose-escalation stage (Phase 1a) followed by Phase 1b safety and cohort expansion. The dose-escalation finds dose-limiting toxicities and recommended Phase 1b dose(s). Phase 1b includes up to 17 disease-specific cohorts; one CLL/SLL cohort may randomize patients between two dose levels until an optimal dose is selected. The study is sequential and not masked.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The listed sites are in France, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Apr 13, 2022
- Primary completion
- January 2027 (estimated)
- Study completion
- January 2028 (estimated)
- Target enrollment
- 572 participants (estimated)
- Last updated on registry
- Jul 2, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Nurix Therapeutics, Inc.
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Additional Site Contact Information 📞 +1 (415) 417-3418 ✉ clinicaltrials@nurixtx.com
Participating sites (62)
- City of HopeRecruiting
Duarte, California, 91010 · United States
- University of California, San FranciscoRecruiting
San Francisco, California, 94143 · United States
- Colorado Blood Cancer InstituteRecruiting
Denver, Colorado, 80218 · United States
- Yale Cancer CenterRecruiting
New Haven, Connecticut, 06510 · United States
- University of MiamiRecruiting
Miami, Florida, 33136 · United States
- Florida Cancer SpecialistsRecruiting
Sarasota, Florida, 34232 · United States
- Winship Cancer Institute of Emory UniversityRecruiting
Atlanta, Georgia, 30322 · United States
- Northwestern UniversityRecruiting
Chicago, Illinois, 60611 · United States
- National Institute of HealthRecruiting
Bethesda, Maryland, 20814 · United States
- Cayuga Medical CenterWithdrawn
Ithaca, New York, 14850 · United States
Terms used on this page · explanations by MedicalUpdates.ai
- first-in-human
- The first study in which a treatment is given to people. Safety is the main question and the number of participants is usually small.
- open-label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- Dose Escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- histologically confirmed
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- prior lines
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- Cohort
- A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- washout period
- A period during which a participant stops a previous treatment before starting the study treatment, so the earlier treatment does not affect the results.
- 5 half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- allogeneic stem cell transplant
- A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
- Chimeric antigen receptor
- A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- Key Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Key Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- relapsed/refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- randomized
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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