A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies
a study on Chronic Lymphocytic Leukemia Leukemia Lymphoma Small Lymphocytic Lymphoma Waldenstrom Macroglobulinemia Mantle Cell Lymphoma Diffuse Large B-Cell Lymphoma Non-Hodgkin Lymphoma
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Location
- at Orange, California and other locations
- Dates
- study startedestimated completion
Description
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.
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
Details
Phase 1a is a dose escalation to 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 1 prior therapy for patients with WM) and for whom no other therapies are known to provide clinical benefit. Phase 1b will investigate the efficacy of NX-2127 at the dose selected in Phase 1a in up to 5 cohorts of patients with R/R B-cell malignancy indications who have received at least 2 prior systemic therapies (or 1 prior therapy for patients with WM): - Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with no BTK C481 mutation - BTK C481 mutation-positive CLL/SLL - Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL) or Waldenstrom Macroglobulinemia (WM) - Follicular lymphoma (FL) - Diffuse Large B-cell Lymphoma (DLBCL)
Keywords
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) BTK Degrader BTK Inhibitor B-cell Malignancy Lymphoma C481 C481S IMiD Lenalidomide Pomalidomide Bruton's Tyrosine Kinase NX-2127 Targeted Protein Degradation Chimeric Targeting Molecule (CTM) Neoplasms Leukemia, Lymphocytic, Chronic, B-Cell Lymphoma, Mantle-Cell Lymphoma, Large B-Cell, Diffuse Waldenstrom Macroglobulinemia
Eligibility
You can join if…
Open to people ages 18 years and up
- 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, or Lugano Classification of Lymphoma response criteria)
- Patients with transformed lymphoma are eligible for the study with the exception of those who have Richter's transformation, prolymphocytic leukemia, or blastoid lymphoma prior to planned start of study drug
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Adequate organ and bone marrow function, in the absence of growth factors
- 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(grade 1 - 3b), and DLBCL (High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements and high-grade B-cell lymphoma NOS)
- Received at least 2 prior systemic therapies (or 1 prior therapy for patients with WM) 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 with no BTK C481 mutation whose disease has failed treatment with a BTKi;
- BTK C481 mutation-positive CLL/SLL whose disease has failed treatment with a BTKi;
- MCL or MZL whose disease has failed treatment with BTKi and an anti-CD20 mAb-based regimen or WM whose disease has failed treatment with BTKi
- FL (grade 1 - 3b) whose disease has failed treatment with anti-CD20 mAb-based regimen;
- DLBCL whose disease has failed treatment with an anti-CD20 mAb-based regimen and an anthracycline (either progressed post stem cell transplant or transplant-ineligible)
- DLBCL histologies include high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements and high-grade B-cell lymphoma NOS
You CAN'T join if...
- History of CNS lymphoma/leukemia in remission for less than 2 years
- Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
- History of known/suspected other autoimmune disease (exception(s): patients with 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 chronic, therapeutic anticoagulation with warfarin or patients treated with dual anti-platelet therapy and vitamin K antagonists
- 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 with the exception of any of the following:
- Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer;
- Adequately treated Stage I cancer from which the patient is currently in remission and has been in remission for ≥ 2 years;
- Low-risk prostate cancer with Gleason score < 7 and prostate-specific antigen < 10 ng/mL; or
- Any other cancer from which the patient has been disease-free for ≥ 2 years
- 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 (> 20 mg/day prednisone or equivalent)
- Clinically significant, uncontrolled cardiac, cardiovascular disease, or history of myocardial infarction within 6 months of planned start of study drug
- Patient is taking strong or moderate cytochrome P450 3A (CYP3A) inducers or inhibitors or inhibitors of P-glycoprotein
Locations
- University of California Irvine
accepting new patients
Orange California 92868 United States - City of Hope
accepting new patients
Duarte California 91010 United States
Details
- Status
- accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Nurix Therapeutics, Inc.
- ID
- NCT04830137
- Phase
- Phase 1 research study
- Study Type
- Interventional
- Participants
- Expecting 130 study participants
- Last Updated
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