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Chronic Lymphocytic Leukemia (CLL)Phase 1NCT04830137

A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies

A Phase 1 study testing NX-2127 in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by Nurix Therapeutics, Inc. at 16 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
NX-2127
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
248 participants
Where
16 sitesUnited States
Study dates
5 May 2021to May 2027
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

  • 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
Show all 16Show fewer
  • Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol
  • 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
  • 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)

Who cannot join

  • 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)
Show all 16Show fewer
  • 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

Trial locations and contacts

16 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Patient Outreach contact

(415)-230-7806 ext. 7806

nx2127001@nurixtx.com

16 sites in 1 country

United States16 sites, 7 recruiting

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20814

    Recruiting

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

    Recruiting

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

    Completed

  • OSU Wexner Medical Center

    Columbus, Ohio, 43210

    Completed

  • Baylor University Medical Center

    Dallas, Texas, 75246

    Completed

  • Sarah Cannon Research Institute at Colorado Blood Cancer Institute

    Denver, Colorado, 80218

    Recruiting

  • City of Hope

    Duarte, California, 91010

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • Mount Sinai Comprehensive Cancer Center

    Miami Beach, Florida, 33140

    Completed

  • Tennessee Oncology

    Nashville, Tennessee, 37203

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Completed

  • University of California Irvine

    Orange, California, 92868

    Completed

  • Huntsman Cancer Institute, University of Utah

    Salt Lake City, Utah, 84112

    Recruiting

  • University of California San Francisco Medical Center

    San Francisco, California, 94143

    Completed

  • Sarah Cannon Research Institute at Florida Cancer Specialists

    Sarasota, Florida, 34203

    Completed

  • Swedish Cancer Institute

    Seattle, Washington, 98104

    Completed

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

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.

Being tested
NX-2127
Keywords
BTK Degrader, BTK Inhibitor, B-cell Malignancy, Lymphoma, IMiD, Lenalidomide, Pomalidomide, Bruton's Tyrosine Kinase, NX-2127, Targeted Protein Degradation, Chimeric Targeting Molecule (CTM), C481, C481S
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Waldenstrom Macroglobulinemia, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Follicular, Lymphoma, Large B-Cell, Diffuse, Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NX-2127Drug

    Oral NX-2127

Study groups in NCT04830137
Study groupRoleWhat they receive
Phase 1a Dose EscalationExperimentalMultiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 1 in CLL or SLL (Dose A)ExperimentalCLL/SLL patients whose disease has failed treatment with a BTK inhibitor
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 1 in MCL (Dose A)ExperimentalMCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 1 in FL, MZL or WM (Dose A)ExperimentalFL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTK inhibitor
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 1 in DLBCL (Dose A)ExperimentalDLBCL patients 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
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 1 in PCNSL (Dose A)ExperimentalPCNSL patients whose disease has failed at least 1 prior line of treatment
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 2 in CLL or SLL (Randomized to Dose A or Dose B)ExperimentalCLL/SLL patients whose disease has failed treatment with a BTK inhibitor
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 2 in MCL (Randomized to Dose A or Dose B)ExperimentalMCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 2 in FL, MZL or WM (Randomized to Dose A or Dose B)ExperimentalFL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTK inhibitor
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 2 in DLBCL (Randomized to Dose A or Dose B)ExperimentalDLBCL patients 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
Receives: Drug: NX-2127
Phase 1b Dose Optimization Stage 2 in PCNSL (Randomized to Dose A or Dose B)ExperimentalPCNSL patients whose disease has failed at least 1 prior line of treatment
Receives: Drug: NX-2127

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with Protocol Specified Dose-Limiting Toxicities

    Phase 1a

    Measured: Up to 24 months

  2. To establish the MTD and/or recommended Phase 1b dosage(s) of NX-2127

    Phase 1a

    Measured: Up to 24 months

  3. To evaluate the clinical activity of NX-2127 at the recommended Phase 1b dosage(s) based on overall response rate (ORR) as assessed by the Investigator

    Phase 1b

    Measured: Up to 4 years

  4. Number of Participants with Adverse Events and Clinical Laboratory Abnormalities

    Phase 1a/1b

    Measured: Up to 5 years

Secondary outcomes (6)

  1. Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration

    Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment

    Measured: Up to 5 years

  2. Duration of response (DOR) as assessed by the Investigator

    Phase 1a/1b

    Measured: Up to 5 years

  3. Progression-free survival (PFS) as assessed by the Investigator

    Phase 1a/1b

    Measured: Up to 5 years

  4. Overall survival (OS) as assessed by the Investigator

    Phase 1b

    Measured: Up to 4 years

  5. To further evaluate the safety and tolerability of NX-2127 by collecting adverse events, treatment emergent adverse events, and incidence of all deaths

    Phase 1b

    Measured: Up to 4 years

  6. Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator

    Phase 1a/1b

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2021
  2. Study start5 May 2021
  3. Primary completionMay 2026 (estimated)
  4. Study completionMay 2027 (estimated)

Resources

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
248 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04830137
Sponsor's protocol ID
NX-2127-001
Status last verified
Mar 2026
First submitted
29 Mar 2021
Last updated
20 Mar 2026
Results posted
No
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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing NX-2127 in people with Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL), run by Nurix Therapeutics, Inc. at 16 sites in United States.

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 16 inclusion and 16 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 20 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. 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 Patient Outreach ((415)-230-7806 ext. 7806, nx2127001@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 4 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 NCT04830137, 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 20 Mar 2026.

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