NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts.
Deyi Zhang, Hailey M Harris, Jonathan Chen...
https://pubmed.ncbi.nlm.nih.gov/36375120Actively Recruiting
Phase 1
Age: 18Years +
All Genders
ID04830137
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
Led by Nurix Therapeutics, Inc. · Updated on 2026-03-20
248
Participants Needed
16
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating NX-2127, an oral drug, in adults with relapsed or refractory B-cell malignancies. This first-in-human Phase 1a/1b open-label study aims to assess the safety, tolerability, and anti-cancer activity of NX-2127 in patients who have had multiple prior treatments and for whom no other therapies are known to provide benefit. The study includes various types of B-cell cancers such as chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, and others. The study consists of two parts: Phase 1a focuses on dose escalation to find the maximum tolerated dose and the recommended dose for Phase 1b. Phase 1b uses a two-stage design to further evaluate safety, tolerability, and preliminary efficacy at selected doses. Stage 1 enrolls about 10 participants per disease group for initial evaluation, while Stage 2 enrolls additional participants randomized to one of two dose levels. Participants receive multiple dose levels of NX-2127 orally, tailored to their specific type of B-cell malignancy and prior treatment history. Participants will be closely monitored for dose-limiting toxicities, adverse events, and clinical laboratory abnormalities for up to five years. Researchers will assess overall response rates, duration of response, progression-free survival, and overall survival as measures of clinical activity. Safety and tolerability data will be collected throughout the study. The study involves regular evaluations, including physical exams, laboratory tests, and disease response assessments, to track participants' health and treatment effects over time.
CONDITIONS
Brief Title
A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Patients must be 18 years of age or older
- Patients must have measurable disease per disease-specific response criteria
- Patients with indolent forms of NHL must meet criteria requiring systemic treatment
- Patients with transformed lymphoma are eligible except those with prolymphocytic leukemia, MCL with blastoid histology, pleomorphic morphology, or known TP53 mutation
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (non-PCNSL) or 0 to 2 (PCNSL patients)
- Adequate organ and bone marrow function
- Patients of child-bearing potential must use adequate contraceptive measures during the study
- Phase 1a patients must have histologically confirmed relapsed/refractory CLL, SLL, WM, MCL, MZL, FL, DLBCL, or PCNSL
- Phase 1a patients must have received at least 2 prior systemic therapies (or at least 1 for WM or PCNSL) with no other therapies known to provide clinical benefit
- Patients must require systemic therapy
- Phase 1b patients must have histologically documented relapsed/refractory B-cell malignancies fitting specified treatment failure criteria per disease type
You will not qualify if you...
- Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
- Known or suspected autoimmune diseases except alopecia, vitiligo, resolved childhood atopic dermatitis, and clinically euthyroid thyroid conditions
- Unable to swallow capsules or conditions interfering with drug delivery, absorption, or metabolism
- Bleeding disorders or other risks for acute blood loss
- Ongoing treatment with warfarin or equivalent within 7 days prior to first dose
- Prior radiotherapy within 2 weeks before starting study drug (except limited palliative radiation)
- Toxicities from previous anticancer therapies not resolved to baseline or Grade 1 (except specified exceptions)
- Active known second malignancy except non-metastatic non-melanoma skin cancer
- Major surgery within 4 weeks before first dose
- Infection with HIV-1 or HIV-2 unless well-controlled
- Active liver disease from any cause
- Active viral reactivation such as CMV or EBV
- Use of systemic corticosteroids exceeding specified doses within 15 days prior to study start
- Use of non-steroidal immunosuppressive drugs within 30 days prior to study start
- Clinically significant uncontrolled cardiac or cardiovascular disease or recent myocardial infarction
- Use of strong CYP3A inducers or inhibitors or P-glycoprotein inhibitors within specified timeframes before first dose
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
screening and enrollment visit
Treatment
Duration - Up to 24 months
Participants receive oral NX-2127 at various dose levels to evaluate safety, tolerability, and preliminary efficacy for relapsed/refractory B-cell malignancies.
Multiple visits for dosing and safety assessments during treatment
Follow-up
Duration - Up to 5 years
Participants are monitored for adverse events, treatment response, and survival outcomes after treatment completion.
Periodic visits over several years for long-term safety and efficacy monitoring
Trial Site Locations
Total: 16 locations
1
City of Hope
Duarte, California, United States, 91010
Actively Recruiting
2
University of California Irvine
Orange, California, United States, 92868
Completed
3
University of California San Francisco Medical Center
San Francisco, California, United States, 94143
Completed
4
Sarah Cannon Research Institute at Colorado Blood Cancer Institute
Denver, Colorado, United States, 80218
Actively Recruiting
5
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, United States, 33140
Completed
6
Sarah Cannon Research Institute at Florida Cancer Specialists
Sarasota, Florida, United States, 34203
Completed
7
The University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Actively Recruiting
8
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20814
Actively Recruiting
9
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Completed
10
University of Cincinnati Medical Center
Cincinnati, Ohio, United States, 45267
Completed
11
OSU Wexner Medical Center
Columbus, Ohio, United States, 43210
Completed
12
Tennessee Oncology
Nashville, Tennessee, United States, 37203
Actively Recruiting
13
Baylor University Medical Center
Dallas, Texas, United States, 75246
Completed
14
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
15
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States, 84112
Actively Recruiting
16
Swedish Cancer Institute
Seattle, Washington, United States, 98104
Completed
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Research Team
P
Patient Outreach
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
11
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