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

NCT ID: NCT04830137

Last Updated: 2025-03-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

248 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-05

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Chronic Lymphocytic Leukemia (CLL) Small Lymphocytic Lymphoma (SLL) Waldenstrom Macroglobulinemia (WM) Mantle Cell Lymphoma (MCL) Marginal Zone Lymphoma (MZL) Follicular Lymphoma (FL) Diffuse Large B-cell Lymphoma (DLBCL) Primary Central Nervous System Lymphoma (PCNSL)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase 1a Dose Escalation

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

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

Group Type EXPERIMENTAL

NX-2127

Intervention Type DRUG

Oral NX-2127

Interventions

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NX-2127

Oral NX-2127

Intervention Type DRUG

Eligibility Criteria

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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)

* 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)

* 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

Exclusion Criteria

* 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


* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Nurix Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Paula O'Connor, MD

Role: STUDY_DIRECTOR

Nurix Therapeutics, Inc.

Locations

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City of Hope

Duarte, California, United States

Site Status RECRUITING

University of California Irvine

Orange, California, United States

Site Status COMPLETED

University of California San Francisco Medical Center

San Francisco, California, United States

Site Status COMPLETED

Sarah Cannon Research Institute at Colorado Blood Cancer Institute

Denver, Colorado, United States

Site Status RECRUITING

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Site Status COMPLETED

Sarah Cannon Research Institute at Florida Cancer Specialists

Sarasota, Florida, United States

Site Status COMPLETED

The University of Chicago Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status COMPLETED

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status COMPLETED

OSU Wexner Medical Center

Columbus, Ohio, United States

Site Status COMPLETED

Tennessee Oncology

Nashville, Tennessee, United States

Site Status RECRUITING

Baylor University Medical Center

Dallas, Texas, United States

Site Status COMPLETED

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Swedish Cancer Institute

Seattle, Washington, United States

Site Status COMPLETED

Countries

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United States

Central Contacts

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Patient Outreach

Role: CONTACT

(415)-230-7806 ext. 7806

References

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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.

Reference Type DERIVED
PMID: 36375120 (View on PubMed)

Other Identifiers

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NX-2127-001

Identifier Type: -

Identifier Source: org_study_id

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