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
1 other identifier
interventional
248
1 country
16
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2021
Longer than P75 for phase_1
16 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 29, 2021
CompletedFirst Posted
Study publicly available on registry
April 2, 2021
CompletedStudy Start
First participant enrolled
May 5, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
May 1, 2027
ExpectedMarch 20, 2026
March 1, 2026
5 years
March 29, 2021
March 18, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of Participants with Protocol Specified Dose-Limiting Toxicities
Phase 1a
Up to 24 months
To establish the MTD and/or recommended Phase 1b dosage(s) of NX-2127
Phase 1a
Up to 24 months
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
Number of Participants with Adverse Events and Clinical Laboratory Abnormalities
Phase 1a/1b
Up to 5 years
Secondary Outcomes (6)
Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration
Up to 5 years
Duration of response (DOR) as assessed by the Investigator
Up to 5 years
Progression-free survival (PFS) as assessed by the Investigator
Up to 5 years
Overall survival (OS) as assessed by the Investigator
Up to 4 years
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 4 years
- +1 more secondary outcomes
Study Arms (11)
Phase 1a Dose Escalation
EXPERIMENTALMultiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose
Phase 1b Dose Optimization Stage 1 in CLL or SLL (Dose A)
EXPERIMENTALCLL/SLL patients whose disease has failed treatment with a BTK inhibitor
Phase 1b Dose Optimization Stage 1 in MCL (Dose A)
EXPERIMENTALMCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen
Phase 1b Dose Optimization Stage 1 in FL, MZL or WM (Dose A)
EXPERIMENTALFL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTK inhibitor
Phase 1b Dose Optimization Stage 1 in DLBCL (Dose A)
EXPERIMENTALDLBCL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen and either: an anthracycline-based regimen; or an anti-CD19-based regimen; or another/palliative regimen
Phase 1b Dose Optimization Stage 1 in PCNSL (Dose A)
EXPERIMENTALPCNSL patients whose disease has failed at least 1 prior line of treatment
Phase 1b Dose Optimization Stage 2 in CLL or SLL (Randomized to Dose A or Dose B)
EXPERIMENTALCLL/SLL patients whose disease has failed treatment with a BTK inhibitor
Phase 1b Dose Optimization Stage 2 in MCL (Randomized to Dose A or Dose B)
EXPERIMENTALMCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen
Phase 1b Dose Optimization Stage 2 in FL, MZL or WM (Randomized to Dose A or Dose B)
EXPERIMENTALFL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTK inhibitor
Phase 1b Dose Optimization Stage 2 in DLBCL (Randomized to Dose A or Dose B)
EXPERIMENTALDLBCL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen and either: an anthracycline-based regimen; or an anti-CD19-based regimen; or another/palliative regimen
Phase 1b Dose Optimization Stage 2 in PCNSL (Randomized to Dose A or Dose B)
EXPERIMENTALPCNSL patients whose disease has failed at least 1 prior line of treatment
Interventions
Oral NX-2127
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
- Have histologically confirmed R/R CLL, SLL, WM, MCL, and MZL, FL, 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
- Must have one of the following histologically documented R/R B-cell malignancies:
- 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
- FL or MZL whose disease has failed treatment with an anti-CD20 mAb-based regimen; or WM whose disease has failed treatment with a BTKi
- 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-based regimen; or an anti-CD19-based regimen, or another/ palliative regimen (either progressed post stem cell transplant or transplant-ineligible)
- 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
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (16)
City of Hope
Duarte, California, 91010, United States
University of California Irvine
Orange, California, 92868, United States
University of California San Francisco Medical Center
San Francisco, California, 94143, United States
Sarah Cannon Research Institute at Colorado Blood Cancer Institute
Denver, Colorado, 80218, United States
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140, United States
Sarah Cannon Research Institute at Florida Cancer Specialists
Sarasota, Florida, 34203, United States
The University of Chicago Medical Center
Chicago, Illinois, 60637, United States
National Institutes of Health Clinical Center
Bethesda, Maryland, 20814, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267, United States
OSU Wexner Medical Center
Columbus, Ohio, 43210, United States
Tennessee Oncology
Nashville, Tennessee, 37203, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, 84112, United States
Swedish Cancer Institute
Seattle, Washington, 98104, United States
Related Publications (1)
Zhang D, Harris HM, Chen J, Judy J, James G, Kelly A, McIntosh J, Tenn-McClellan A, Ambing E, Tan YS, Lu H, Gajewski S, Clifton MC, Yung S, Robbins DW, Pirooznia M, Skanland SS, Gaglione E, Mhibik M, Underbayev C, Ahn IE, Sun C, Herman SEM, Noviski M, Wiestner A. NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts. Blood. 2023 Mar 30;141(13):1584-1596. doi: 10.1182/blood.2022016934.
PMID: 36375120DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Study Director
Nurix Therapeutics, Inc.
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 29, 2021
First Posted
April 2, 2021
Study Start
May 5, 2021
Primary Completion
May 1, 2026
Study Completion (Estimated)
May 1, 2027
Last Updated
March 20, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share