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

Chronic Lymphocytic Leukemia (CLL) Clinical Trial

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 Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04830137
• Other study ID #: NX-2127-001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: May 5, 2021
• Est. completion date: December 2025

Study information

• Verified date: November 2023
• Source: Nurix Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 at least 1 prior therapy for patients with WM or PCNSL) and for whom no other therapies are known to provide clinical benefit. Phase 1b will investigate the efficacy of NX-2127 at the dosage(s) 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 at least 1 prior therapy for patients with WM or PCNSL):

• Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with no BTK C481 mutation

• BTK C481 mutation-positive CLL/SLL

• Mantle Cell Lymphoma (MCL)

• Follicular lymphoma (FL) or Marginal Zone Lymphoma (MZL); or Primary Central Nervous System Lymphoma (PCNSL)

• Diffuse Large B-cell Lymphoma (DLBCL) or Waldenstrom Macroglobulinemia (WM)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 160
• Est. completion date: December 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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, Lugano Classification of Lymphoma response criteria, or International PCNSL Collaborative Group response criteria)

• Patients with transformed lymphoma are eligible for the study with the exception of those who have prolymphocytic leukemia, MCL with blastoid histology, MCL with pleomorphic morphology, or MCL with known TP53 mutation

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (non-PCNSL indications) or 0 - 2 (PCNSL patients)

• Adequate organ and bone marrow function

• 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), DLBCL, or PCNSL

• Received at least 2 prior systemic therapies (or at least 1 prior therapy for patients with WM or PCNSL) 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 whose disease has failed treatment with BTKi and an anti-CD20 mAb-based regimen, excluding patients with blastoid morphology, pleomorphic morphology, or a known TP53 mutation

• FL (grade 1 - 3b) or MZL whose disease has failed treatment with anti-CD20 mAb-based regimen; or PCNSL whose disease failed at least 1 prior line of treatment

• DLBCL whose disease has failed treatment with an anti-CD20 mAb-based regimen and either: an anthracycline, an anti-CD19-based regimen, or another/ palliative regimen (either progressed post stem cell transplant or transplant-ineligible); or WM whose disease has failed treatment with a BTKi

Exclusion Criteria:

• History of central nervous system (CNS) lymphoma/leukemia in remission for less than 2 years (non-PCNSL indications) or evidence of disease outside of the CNS (other than ocular involvement) or disease involving the brain stem (PCNSL patients)

• Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia

• History of known/suspected other autoimmune disease (exception(s): patients with alopecia, 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 warfarin or an equivalent vitamin K antagonist and within 7 days prior to the first dose of study drug

• 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

• 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 exceeding 20 mg/day prednisone (or equivalent) for non-PCNSL indications within 15 days prior to the planned start of study drug. PCNSL patients may not exceed corticosteroid doses of 40 mg/day prednisone (or equivalent) and should be on a stable or decreasing dose for 7 days prior to planned study start.

• Use of non-steroidal immunosuppressive drugs within 30 days prior to start of the study

• Clinically significant, uncontrolled cardiac, cardiovascular disease, or history of myocardial infarction within 6 months of planned start of study drug

• Administration of any strong cytochrome P450 3A (CYP3A) inducers or inhibitors for 14 days prior to the first dose of study drug, and any P-glycoprotein inhibitors or moderate inducers of CYP3A for 7 days

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia (CLL)
• Diffuse Large B-cell Lymphoma (DLBCL)
• Follicular Lymphoma (FL)
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma (MCL)
• Marginal Zone Lymphoma (MZL)
• Neoplasms
• Primary Central Nervous System Lymphoma (PCNSL)
• Small Lymphocytic Lymphoma (SLL)
• Waldenstrom Macroglobulinemia
• Waldenstrom Macroglobulinemia (WM)

Intervention

Drug:
• NX-2127
Oral NX-2127

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	The University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Baylor University Medical Center	Dallas	Texas
United States	Sarah Cannon Research Institute at Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Mount Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Sarah Cannon Research Institute at Tennessee Oncology	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of California Irvine	Orange	California
United States	Huntsman Cancer Institute, University of Utah	Salt Lake City	Utah
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Sarah Cannon Research Institute at Florida Cancer Specialists	Sarasota	Florida
United States	Swedish Cancer Institute	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Nurix Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with Protocol Specified Dose-Limiting Toxicities	Phase 1a	Up to 24 months
Primary	To establish the MTD and/or recommended Phase 1b dosage(s) of NX-2127	Phase 1a	Up to 24 months
Primary	To evaluate the clinical activity of NX-2127 at the recommended Phase 1b dosage(s) based on overall response rate (ORR) as assessed by the Investigator	Phase 1b	Up to 4 years
Primary	Number of Participants with Adverse Events and Clinical Laboratory Abnormalities	Phase 1a/1b	Up to 5 years
Secondary	Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration	Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment	Up to 5 years
Secondary	Duration of response (DOR) as assessed by the Investigator	Phase 1a/1b	Up to 5 years
Secondary	Progression-free survival (PFS) as assessed by the Investigator	Phase 1a/1b	Up to 5 years
Secondary	Overall survival (OS) as assessed by the Investigator	Phase 1b	Up to 4 years
Secondary	To further evaluate the safety and tolerability of NX-2127 by collecting adverse events, treatment emergent adverse events, and incidence of all deaths	Phase 1b	Up to 4 years
Secondary	Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator	Phase 1a/1b	Up to 5 years