Tests NX-2127 in adults with returning or resistant B-cell blood cancers

Trial details

Who runs it

Nurix Therapeutics, Inc.

Trial code

NCT04830137

Record updated

20 March 2026

Original 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.Read full original descriptionShow less

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.

Inclusion: 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).

Exclusion: 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); Patient has had major surgery (e.g. requiring general anesthesia) within 4 weeks before the planned first dose of study drug; 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; 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; 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; Active known second malignancy. Exception: patients with non-metastatic, non-melanoma skin cancer are eligible; 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; Clinically significant, uncontrolled cardiac, cardiovascular disease, or history of myocardial infarction within 6 months of planned start of study drug; Active viral reactivation (e.g., CMV or EBV).

ClinicalTrials.gov NCT04830137