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

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

Sponsors

Lead Sponsor: Nurix Therapeutics, Inc.

Source 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.

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)

Overall Status Recruiting
Start Date 2021-05-05
Completion Date 2023-11-01
Primary Completion Date 2023-10-01
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of Participants with Protocol Specified Dose-Limiting Toxicities 10 months
To establish the MTD and/or recommended Phase 1b dose of NX-2127 10 months
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 Up to 24 months
Number of Participants with Adverse Events and Clinical Laboratory Abnormalities Up to 3 years
Secondary Outcome
Measure Time Frame
Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration Up to 3 years
Duration of response (DOR) as assessed by the Investigator Up to 3 Years
Progression-free survival (PFS) as assessed by the Investigator Up to 3 Years
Overall survival (OS) as assessed by the Investigator Up to 24 months
To further evaluate the safety and tolerability of NX-2127 by collecting adverse events, treatment emergent adverse events, and incidence of all deaths Up to 24 months
Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator Up to 3 years
Enrollment 130
Condition
Intervention

Intervention Type: Drug

Intervention Name: NX-2127

Description: Oral 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

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Official
Last Name Role Affiliation
Robert J Brown, MD Study Director Nurix Therapeutics, Inc.
Overall Contact

Last Name: Patient Outreach

Phone: (415)-230-7806

Phone Ext.: 7806

Email: [email protected]

Location
Facility: Status:
City of Hope | Duarte, California, 91010, United States Recruiting
University of California Irvine | Orange, California, 92868, United States Recruiting
Sarah Cannon Research Institute at Colorado Blood Cancer Institute | Denver, Colorado, 80218, United States Recruiting
Sarah Cannon Research Institute at Florida Cancer Specialists | Sarasota, Florida, 34203, United States Recruiting
Memorial Sloan Kettering Cancer Center | New York, New York, 10065, United States Recruiting
Sarah Cannon Research Institute at Tennessee Oncology | Nashville, Tennessee, 37203, United States Recruiting
MD Anderson Cancer Center | Houston, Texas, 77030, United States Recruiting
Location Countries

United States

Verification Date

2021-08-01

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 6
Arm Group

Label: Phase 1a Dose Escalation

Type: Experimental

Description: Multiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose

Label: Phase 1b Dose Expansion in CLL or SLL with no BTK C481 mutation

Type: Experimental

Description: CLL/SLL patients with no BTK C481 mutation whose disease has failed treatment with a BTK inhibitor

Label: Phase 1b Dose Expansion in BTK C481 mutation-positive CLL/SLL

Type: Experimental

Description: BTK C481 mutation-positive CLL/SLL patients whose disease has failed treatment with a BTK inhibitor

Label: Phase 1b Dose Expansion in MCL, MZL or WM

Type: Experimental

Description: MCL, MZL, or WM patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen

Label: Phase 1b Dose Expansion in FL

Type: Experimental

Description: FL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen

Label: Phase 1b Dose Expansion in DLBCL

Type: Experimental

Description: DLBCL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen and an anthracycline

Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

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