RECRUITING

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

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2021-05-05

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04830137

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 * 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, 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

Inclusion Criteria

Exclusion 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
* 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, 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

Contacts and Locations

Study Contact

Patient Outreach

CONTACT

(415)-230-7806

nx2127001@nurixtx.com

Principal Investigator

Paula O'Connor, MD

STUDY_DIRECTOR

Nurix Therapeutics, Inc.

Study Locations (Sites)

City of Hope

Duarte, California, 91010

United States

University of California Irvine

Orange, California, 92868

United States

University of California San Francisco Medical Center

San Francisco, California, 94143

United States

Sarah Cannon Research Institute at Colorado Blood Cancer Institute

Denver, Colorado, 80218

United States

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140

United States

Sarah Cannon Research Institute at Florida Cancer Specialists

Sarasota, Florida, 34203

United States

The University of Chicago Medical Center

Chicago, Illinois, 60637

United States

National Institutes of Health Clinical Center

Bethesda, Maryland, 20814

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267

United States

OSU Wexner Medical Center

Columbus, Ohio, 43210

United States

Tennessee Oncology

Nashville, Tennessee, 37203

United States

Baylor University Medical Center

Dallas, Texas, 75246

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Huntsman Cancer Institute, University of Utah

Salt Lake City, Utah, 84112

United States

Swedish Cancer Institute

Seattle, Washington, 98104

United States

Collaborators and Investigators

Sponsor: Nurix Therapeutics, Inc.

Paula O'Connor, MD, STUDY_DIRECTOR, Nurix Therapeutics, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-05-05

Study Completion Date2026-12

Study Record Updates

Study Start Date2021-05-05

Study Completion Date2026-12

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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)

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

Conditions

Quick Navigation

Study Overview

Description

Official Title

Quick Facts

Study ID

Participation Criteria

Contacts and Locations

Study Contact

Principal Investigator

Study Locations (Sites)

Collaborators and Investigators

Study Record Dates

Study Registration Dates

Study Record Updates

Terms related to this study

Keywords Provided by Researchers

Additional Relevant MeSH Terms