Recruiting
Phase 1

NX-2127

Sponsor:

Nurix Therapeutics, Inc.

Code:

NCT04830137

Conditions

Chronic Lymphocytic Leukemia (CLL)

Small Lymphocytic Lymphoma (SLL)

Waldenstrom Macroglobulinemia (WM)

Mantle Cell Lymphoma (MCL)

Marginal Zone Lymphoma (MZL)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

NX-2127

Study Details

Brief 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.

Conditions

Chronic Lymphocytic Leukemia (CLL)

Small Lymphocytic Lymphoma (SLL)

Waldenstrom Macroglobulinemia (WM)

Mantle Cell Lymphoma (MCL)

Marginal Zone Lymphoma (MZL)

Study ID

NCT04830137

Start date

May 5, 2021

Status verified date

Mar, 2026

Completion date

May, 2027

Anticipated

Primary completion date

May, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Exclusion Criteria:

  • 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 Design

Enrollment

248 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1a Dose Escalation

Multiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose

experimental: Phase 1b Dose Optimization Stage 1 in CLL or SLL (Dose A)

CLL/SLL patients whose disease has failed treatment with a BTK inhibitor

experimental: Phase 1b Dose Optimization Stage 1 in MCL (Dose A)

MCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen

experimental: Phase 1b Dose Optimization Stage 1 in FL, MZL or WM (Dose A)

FL 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

experimental: Phase 1b Dose Optimization Stage 1 in DLBCL (Dose A)

DLBCL 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

experimental: Phase 1b Dose Optimization Stage 1 in PCNSL (Dose A)

PCNSL patients whose disease has failed at least 1 prior line of treatment

experimental: Phase 1b Dose Optimization Stage 2 in CLL or SLL (Randomized to Dose A or Dose B)

CLL/SLL patients whose disease has failed treatment with a BTK inhibitor

experimental: Phase 1b Dose Optimization Stage 2 in MCL (Randomized to Dose A or Dose B)

MCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen

experimental: Phase 1b Dose Optimization Stage 2 in FL, MZL or WM (Randomized to Dose A or Dose B)

FL 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

experimental: Phase 1b Dose Optimization Stage 2 in DLBCL (Randomized to Dose A or Dose B)

DLBCL 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

experimental: Phase 1b Dose Optimization Stage 2 in PCNSL (Randomized to Dose A or Dose B)

PCNSL patients whose disease has failed at least 1 prior line of treatment

Interventions

NX-2127

Oral NX-2127

Primary outcome measure

  • Number of Participants with Protocol Specified Dose-Limiting Toxicities [ Time Frame: Up to 24 months ]
  • To establish the MTD and/or recommended Phase 1b dosage(s) of NX-2127 [ Time Frame: Up to 24 months ]
  • 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 [ Time Frame: Up to 4 years ]
  • Number of Participants with Adverse Events and Clinical Laboratory Abnormalities [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

Patient Outreach

(415)-230-7806nx2127001@nurixtx.com

Locations

City of Hope

Recruiting

Duarte, California, United States, 91010

Sarah Cannon Research Institute at Colorado Blood Cancer Institute

Recruiting

Denver, Colorado, United States, 80218

The University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637

National Institutes of Health Clinical Center

Recruiting

Bethesda, Maryland, United States, 20814

Tennessee Oncology

Recruiting

Nashville, Tennessee, United States, 37203

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Huntsman Cancer Institute, University of Utah

Recruiting

Salt Lake City, Utah, United States, 84112

More Information

Sponsor

Nurix Therapeutics, Inc.

Last update posted

Mar 20, 2026

Last verified

Mar, 2026

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-27. This information was provided to ClinicalTrials.gov by Nurix Therapeutics, Inc. on 2026-03-20. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.