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

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ClinicalTrials.gov Identifier: NCT04830137
Recruitment Status : Recruiting
First Posted : April 2, 2021
Last Update Posted : August 9, 2021
Sponsor:
Information provided by (Responsible Party):
Nurix Therapeutics, Inc.

Brief 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.

Condition or disease Intervention/treatment Phase
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) Drug: NX-2127 Phase 1

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)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 5, 2021
Estimated Primary Completion Date : October 2023
Estimated Study Completion Date : November 2023


Arm Intervention/treatment
Experimental: Phase 1a Dose Escalation
Multiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose
Drug: NX-2127
Oral NX-2127

Experimental: Phase 1b Dose Expansion in CLL or SLL with no BTK C481 mutation
CLL/SLL patients with no BTK C481 mutation whose disease has failed treatment with a BTK inhibitor
Drug: NX-2127
Oral NX-2127

Experimental: Phase 1b Dose Expansion in BTK C481 mutation-positive CLL/SLL
BTK C481 mutation-positive CLL/SLL patients whose disease has failed treatment with a BTK inhibitor
Drug: NX-2127
Oral NX-2127

Experimental: Phase 1b Dose Expansion in MCL, MZL or WM
MCL, MZL, or WM patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen
Drug: NX-2127
Oral NX-2127

Experimental: Phase 1b Dose Expansion in FL
FL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen
Drug: NX-2127
Oral NX-2127

Experimental: Phase 1b Dose Expansion in DLBCL
DLBCL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen and an anthracycline
Drug: NX-2127
Oral NX-2127




Primary Outcome Measures :
  1. Number of Participants with Protocol Specified Dose-Limiting Toxicities [ Time Frame: 10 months ]
    Phase 1a

  2. To establish the MTD and/or recommended Phase 1b dose of NX-2127 [ Time Frame: 10 months ]
    Phase 1a

  3. To evaluate the clinical activity of NX-2127 at the recommended Phase 1b dose based on overall response rate (ORR) as assessed by the Investigator [ Time Frame: Up to 24 months ]
    Phase 1b

  4. Number of Participants with Adverse Events and Clinical Laboratory Abnormalities [ Time Frame: Up to 3 years ]
    Phase 1a/1b


Secondary Outcome Measures :
  1. Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration [ Time Frame: Up to 3 years ]
    Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment

  2. Duration of response (DOR) as assessed by the Investigator [ Time Frame: Up to 3 Years ]
    Phase 1a/1b

  3. Progression-free survival (PFS) as assessed by the Investigator [ Time Frame: Up to 3 Years ]
    Phase 1a/1b

  4. Overall survival (OS) as assessed by the Investigator [ Time Frame: Up to 24 months ]
    Phase 1b

  5. 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 ]
    Phase 1b

  6. Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator [ Time Frame: Up to 3 years ]
    Phase 1a/1b



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04830137


Contacts
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Contact: Patient Outreach (415)-230-7806 ext 7806 nx2127001@nurixtx.com

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
University of California Irvine Recruiting
Orange, California, United States, 92868
United States, Colorado
Sarah Cannon Research Institute at Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States, 80218
United States, Florida
Sarah Cannon Research Institute at Florida Cancer Specialists Recruiting
Sarasota, Florida, United States, 34203
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
United States, Tennessee
Sarah Cannon Research Institute at Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Nurix Therapeutics, Inc.
Investigators
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Study Director: Robert J Brown, MD Nurix Therapeutics, Inc.
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Responsible Party: Nurix Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04830137    
Other Study ID Numbers: NX-2127-001
First Posted: April 2, 2021    Key Record Dates
Last Update Posted: August 9, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nurix Therapeutics, Inc.:
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)
Additional relevant MeSH terms:
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Lymphoma
Neoplasms
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell
Lymphoma, B-Cell
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders