ClinicalTrials.gov record NCT04830137
A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies
A Phase 1, Dose Escalation, Safety and Tolerability Study of NX-2127, 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 Phase 1, open-label study evaluates oral NX-2127 in adults with relapsed or refractory B‑cell malignancies (CLL, SLL, WM, MCL, MZL, FL, DLBCL, PCNSL). Phase 1a uses dose escalation to assess safety and identify dose(s) for Phase 1b. Phase 1b is a two-stage dose‑optimization part; Stage 2 randomly assigns participants between two dose levels.
What it is studying. The study is testing how safe and tolerable NX-2127 is and whether it shows anti-cancer activity in several relapsed/refractory B‑cell malignancies. It also collects information on drug levels in the blood (pharmacokinetics) and measures clinical outcomes such as response, duration of response, progression-free survival, and overall survival as specified in the protocol.
What the researchers hope to learn. Scientific goals are to evaluate safety and tolerability, identify the maximum tolerated dose and recommended Phase 1b dose(s), assess clinical activity by overall response rate, characterize adverse events and laboratory abnormalities, and collect pharmacokinetic and clinical outcome data (duration of response, progression-free survival, overall survival).
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 oncology study designed to evaluate the safety and anti-cancer activity of NX-2127 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-2127
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Patients must be ≥ 18 years of age
- Patients must have measurable disease per disease-specific response criteria
- Patients with indolent forms of NHL must meet the criteria requiring systemic treatment (i.e., iwCLL, IWG, Lugano Classification of Lymphoma response criteria, or International PCNSL Collaborative Group response criteria)
- Patients with transformed lymphoma are eligible for the study with the exception of those detailed in
Exclusion criteria
- #1: Prolymphocytic leukemia, MCL with blastoid histology, MCL with pleomorphic morphology, or MCL with known TP53 mutation
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (non-PCNSL indications) or 0 - 2 (PCNSL patients)
- Adequate organ and bone marrow function
- Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol
- Inclusion Criteria for Patients in Phase 1a:
- Have histologically confirmed R/R CLL, SLL, WM, MCL, and MZL, FL, DLBCL, or PCNSL
- Received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL) and have no other therapies known to provide clinical benefit
- Must require systemic therapy
- Inclusion Criteria for Patients in Phase 1b:
- Must have one of the following histologically documented R/R B-cell malignancies:
- CLL/SLL whose disease has failed treatment with a BTKi;
- MCL whose disease has failed treatment with BTKi and an anti-CD20 mAb-based regimen
- FL or MZL whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTKi
- PCNSL whose disease failed at least 1 prior line of treatment
- DLBCL whose disease has failed treatment with an anti-CD20 mAb-based regimen and either: an anthracycline-based regimen; or an anti-CD19-based regimen, or another/ palliative regimen (either progressed post stem cell transplant or transplant-ineligible)
- Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
- History of known/suspected other autoimmune disease (exception(s): patients with alopecia, vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at screening are allowed.)
- Unable to swallow capsules or have a condition that may interfere in the delivery, absorption, or metabolism of the study drug
- Bleeding diathesis, or other known risk for acute blood loss
- Patients requiring ongoing treatment with warfarin or an equivalent vitamin K antagonist and within 7 days prior to the first dose of study drug
- Prior radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation)
- Toxicities from previous anticancer therapies must have resolved to baseline levels or to Grade 1 (except for alopecia, hypothyroidism with adequate replacement therapy, hypopituitarism with adequate replacement therapy, peripheral neuropathy or hematologic parameters meeting inclusion criteria).
- Active known second malignancy. Exception: patients with non-metastatic, non-melanoma skin cancer are eligible
- Patient has had major surgery (e.g. requiring general anesthesia) within 4 weeks before the planned first dose of study drug
- Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: patients with well-controlled HIV (e.g., CD4 > 350/mm3 and undetectable viral load) are eligible.
- Current active liver disease from any cause
- Active viral reactivation (e.g., CMV or EBV)
- Use of systemic corticosteroids exceeding 20 mg/day prednisone (or equivalent) for non-PCNSL indications within 15 days prior to the planned start of study drug. PCNSL patients may not exceed corticosteroid doses of 40 mg/day prednisone (or equivalent) and should be on a stable or decreasing dose for 7 days prior to planned study start.
- Use of non-steroidal immunosuppressive drugs within 30 days prior to start of the study
- Clinically significant, uncontrolled cardiac, cardiovascular disease, or history of myocardial infarction within 6 months of planned start of study drug
- Administration of any strong cytochrome P450 3A (CYP3A) inducers or inhibitors for 14 days prior to the first dose of study drug, and any P-glycoprotein inhibitors (for 2 days) or moderate inducers of CYP3A for 7 days
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
Phase 1a (Dose Escalation) will evaluate the safety and tolerability of NX-2127 in adult patients with relapsed/refractory (R/R) B-cell malignancies, who have required and received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL) and for which no other therapies are known to provide clinical benefit. Phase 1b (Dose Optimization) will use a 2-stage design to further investigate the safety, tolerability, and preliminary efficacy of NX-2127 in R/R B-cell malignancies based on the dosage(s) selected in Phase 1a. Stage 1 will enroll approximately 10 participants per group based on B-cell lymphoma/leukemia indication at a specific dose selected from the first part of the study. The Sponsor may decide to open Stage 2 for any given group after review of safety and anti-tumor activity data from Stage 1. In Stage 2, an additional 10 participants will be enrolled at the dose from Stage 1 as well as 20 additional participants at a second alternative dose. Participants will be randomly assigned to one of the 2 dose levels in Stage 2.
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 take oral NX-2127 and make regular clinic visits for safety checks and assessments of their disease. The study team will collect samples for drug-level (pharmacokinetic) testing at specified times (after the first dose, before and after doses in selected treatment cycles, and at the end of treatment) and will record side effects and laboratory results. Disease response will be evaluated using disease-specific response criteria. In Phase 1a doses are escalated to identify a recommended dose; in Phase 1b some groups may be randomized to one of two dose levels, and monitoring/assessments may continue for months to years as specified by the study.
How the study is structured. This is an interventional (treatment) study of an oral drug. Phase 1a is an open-label dose-escalation stage to find dose-limiting toxicities and recommend dose(s) for Phase 1b. Phase 1b uses a two-stage design: Stage 1 enrolls groups by disease at a selected dose; Stage 2 may open to enroll more participants and randomize them between two dose levels. All arms receive NX-2127; there is no masking.
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 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
- May 5, 2021
- Primary completion
- May 2026 (estimated)
- Study completion
- May 2027 (estimated)
- Target enrollment
- 248 participants (estimated)
- Last updated on registry
- Mar 20, 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.
- Patient Outreach 📞 (415)-230-7806 ext. 7806 ✉ nx2127001@nurixtx.com
Participating sites (16)
- City of HopeRecruiting
Duarte, California, 91010 · United States
- University of California IrvineCompleted
Orange, California, 92868 · United States
- University of California San Francisco Medical CenterCompleted
San Francisco, California, 94143 · United States
- Sarah Cannon Research Institute at Colorado Blood Cancer InstituteRecruiting
Denver, Colorado, 80218 · United States
- Mount Sinai Comprehensive Cancer CenterCompleted
Miami Beach, Florida, 33140 · United States
- Sarah Cannon Research Institute at Florida Cancer SpecialistsCompleted
Sarasota, Florida, 34203 · United States
- The University of Chicago Medical CenterRecruiting
Chicago, Illinois, 60637 · United States
- National Institutes of Health Clinical CenterRecruiting
Bethesda, Maryland, 20814 · United States
- Memorial Sloan Kettering Cancer CenterCompleted
New York, New York, 10065 · United States
- University of Cincinnati Medical CenterCompleted
Cincinnati, Ohio, 45267 · 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.
- 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.
- 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.
- 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 therapy
- 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.
- 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.
- at screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- 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.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- 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.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- Dose Escalation
- Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
- 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.
- Sponsor
- The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
- randomly assigned
- 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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