Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UC Irvine
Dates
study started
estimated 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
Study Type
Interventional
Last Updated