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 Neoplasms
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Location
- at Orange, California and other locations
- Dates
- study startedcompletion around
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 (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.
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), Primary Central Nervous System Lymphoma (PCNSL), 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, Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell, Mantle-Cell Lymphoma, 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, 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
You CAN'T join if...
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
Locations
- University of California Irvine
in progress, not accepting new patients
Orange California 92868 United States - City of Hope
accepting new patients
Duarte California 91010 United States - Huntsman Cancer Institute, University of Utah
accepting new patients
Salt Lake City Utah 84112 United States
Details
- Status
- accepting new patients at some sites,
but this study is not currently recruiting here - Start Date
- Completion Date
- (estimated)
- Sponsor
- Nurix Therapeutics, Inc.
- ID
- NCT04830137
- Phase
- Phase 1 research study
- Study Type
- Interventional
- Participants
- Expecting 248 study participants
- Last Updated