Clinical Trials /

A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies

NCT04830137

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.

Related Conditions:
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • High Grade B-Cell Lymphoma with MYC and BCL2 and/or BCL6 Rearrangements
  • High Grade B-Cell Lymphoma, Not Otherwise Specified
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Waldenstrom Macroglobulinemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of NX-2127 in Adults With Relapsed/Refractory 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

Clinical Trial IDs

  • ORG STUDY ID: NX-2127-001
  • NCT ID: NCT04830137

Conditions

  • 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)

Interventions

DrugSynonymsArms
NX-2127Phase 1a Dose Escalation

Purpose

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.

Detailed Description

      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)
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1a Dose EscalationExperimentalMultiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose
  • NX-2127
Phase 1b Dose Expansion in CLL or SLL with no BTK C481 mutationExperimentalCLL/SLL patients with no BTK C481 mutation whose disease has failed treatment with a BTK inhibitor
  • NX-2127
Phase 1b Dose Expansion in BTK C481 mutation-positive CLL/SLLExperimentalBTK C481 mutation-positive CLL/SLL patients whose disease has failed treatment with a BTK inhibitor
  • NX-2127
Phase 1b Dose Expansion in MCL, MZL or WMExperimentalMCL, MZL, or WM patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen
  • NX-2127
Phase 1b Dose Expansion in FLExperimentalFL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen
  • NX-2127
Phase 1b Dose Expansion in DLBCLExperimentalDLBCL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen and an anthracycline
  • NX-2127

Eligibility Criteria

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants with Protocol Specified Dose-Limiting Toxicities
Time Frame:10 months
Safety Issue:
Description:Phase 1a

Secondary Outcome Measures

Measure:Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration
Time Frame:Up to 3 years
Safety Issue:
Description:Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment
Measure:Duration of response (DOR) as assessed by the Investigator
Time Frame:Up to 3 Years
Safety Issue:
Description:Phase 1a/1b
Measure:Progression-free survival (PFS) as assessed by the Investigator
Time Frame:Up to 3 Years
Safety Issue:
Description:Phase 1a/1b
Measure:Overall survival (OS) as assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:Phase 1b
Measure:To further evaluate the safety and tolerability of NX-2127 by collecting adverse events, treatment emergent adverse events, and incidence of all deaths
Time Frame:Up to 24 months
Safety Issue:
Description:Phase 1b
Measure:Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator
Time Frame:Up to 3 years
Safety Issue:
Description:Phase 1a/1b

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Nurix Therapeutics, Inc.

Trial Keywords

  • 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)

Last Updated

June 23, 2021