Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UC Irvine UCSF
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
  • University of California San Francisco Medical Center accepting new patients
    San Francisco California 94143 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
Last Updated