A Study of NX-2127 in Adults With Relapsed/Refractory B-cell Malignancies
Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Waldenstrom Macroglobulinemia (WM)
About this trial
This is an interventional treatment trial for Chronic Lymphocytic Leukemia (CLL) focused on measuring BTK Degrader, BTK Inhibitor, B-cell Malignancy, Lymphoma, C481, C481S, IMiD, Lenalidomide, Pomalidomide, Bruton's Tyrosine Kinase, NX-2127, Targeted Protein Degradation, Chimeric Targeting Molecule (CTM)
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, 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), non-GCB 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
- FL (grade 1 - 3b) or MZL whose disease has failed treatment with anti-CD20 mAb-based regimen; or PCNSL whose disease failed treatment with a BTKi
- Non-GCB 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) or WM whose disease has failed treatment with 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
Sites / Locations
- City of HopeRecruiting
- University of California IrvineRecruiting
- University of California San Francisco Medical CenterRecruiting
- Sarah Cannon Research Institute at Colorado Blood Cancer InstituteRecruiting
- Mount Sinai Comprehensive Cancer CenterRecruiting
- Sarah Cannon Research Institute at Florida Cancer SpecialistsRecruiting
- The University of Chicago Medical CenterRecruiting
- National Institutes of Health Clinical CenterRecruiting
- Memorial Sloan Kettering Cancer CenterRecruiting
- University of Cincinnati Medical CenterRecruiting
- OSU Wexner Medical CenterRecruiting
- Sarah Cannon Research Institute at Tennessee OncologyRecruiting
- Baylor University Medical CenterRecruiting
- MD Anderson Cancer CenterRecruiting
- Huntsman Cancer Institute, University of UtahRecruiting
- Swedish Cancer InstituteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Phase 1a Dose Escalation
Phase 1b Dose Expansion in CLL or SLL with no BTK C481 mutation
Phase 1b Dose Expansion in BTK C481 mutation-positive CLL/SLL
Phase 1b Dose Expansion in MCL
Phase 1b Dose Expansion in FL, MZL or PCNSL
Phase 1b Dose Expansion in DLBCL or WM
Multiple dose levels of NX-2127 to be evaluated; determination of MTD/Phase 1b recommended dose
CLL/SLL patients with no BTK C481 mutation whose disease has failed treatment with a BTK inhibitor
BTK C481 mutation-positive CLL/SLL patients whose disease has failed treatment with a BTK inhibitor
MCL patients whose disease has failed treatment with a BTK inhibitor and an anti-CD20 monoclonal antibody (mAb) based regimen
FL or MZL patients whose disease has failed treatment with an anti-CD20 mAb-based regimen; or PCNSL whose disease has failed at least 1 prior line of treatment
DLBCL patients 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; or WM patients whose disease has failed treatment with a BTK inhibitor