Chronic Lymphocytic Leukemia (CLL), Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), Marginal Zone Lymphoma (MZL), Primary Central Nervous System Lymphoma (PCNSL), Small Lymphocytic Lymphoma (SLL), Waldenstrom Macroglobulinemia (WM)
Conditions
Keywords
BTK Degrader, BTK Inhibitor, B-cell Malignancy, Lymphoma, IMiD, Lenalidomide, Pomalidomide, Bruton's Tyrosine Kinase, NX-2127, Targeted Protein Degradation, Chimeric Targeting Molecule (CTM), C481, C481S
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 (Dose Escalation) will 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 which no other therapies are known to provide clinical benefit. Phase 1b (Dose Optimization) will use a 2-stage design to further investigate the safety, tolerability, and preliminary efficacy of NX-2127 in R/R B-cell malignancies based on the dosage(s) selected in Phase 1a. Stage 1 will enroll approximately 10 participants per group based on B-cell lymphoma/leukemia indication at a specific dose selected from the first part of the study. The Sponsor may decide to open Stage 2 for any given group after review of safety and anti-tumor activity data from Stage 1. In Stage 2, an additional 10 participants will be enrolled at the dose from Stage 1 as well as 20 additional participants at a second alternative dose. Participants will be randomly assigned to one of the 2 dose levels in Stage 2.
Interventions
DRUGNX-2127
Oral NX-2127
Sponsors
Nurix Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 detailed in
Exclusion criteria
#1: 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, 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 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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Protocol Specified Dose-Limiting Toxicities | Up to 24 months | Phase 1a |
| To establish the MTD and/or recommended Phase 1b dosage(s) of NX-2127 | Up to 24 months | Phase 1a |
| 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 | Up to 4 years | Phase 1b |
| Number of Participants with Adverse Events and Clinical Laboratory Abnormalities | Up to 5 years | Phase 1a/1b |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Profile of NX-2127: Maximum Serum Concentration | Up to 5 years | Phase 1a/1b - Sampling following the first dose, pre and post-dose at selected cycles, and at the end of treatment |
| Duration of response (DOR) as assessed by the Investigator | Up to 5 years | Phase 1a/1b |
| Progression-free survival (PFS) as assessed by the Investigator | Up to 5 years | Phase 1a/1b |
| Overall survival (OS) as assessed by the Investigator | Up to 4 years | Phase 1b |
| 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 | Phase 1b |
| Complete response (CR) rate / CR with incomplete marrow recovery as assessed by the Investigator | Up to 5 years | Phase 1a/1b |
Countries
United States
Contacts
CONTACTPatient Outreach
STUDY_DIRECTORStudy Director
Nurix Therapeutics, Inc.
Outcome results
None listed