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 NX-2127

What's the purpose of this trial?

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.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

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

Additional Trial Information

Phase 1

Enrollment: 160 patients (estimated)

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.


City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

Chao Family Comprehensive Cancer Center University of California, Irvine

Orange, CA

Open and Accepting

UCSF Medical Center (Parnassus)

San Francisco, CA

Open and Accepting



Florida Cancer Specialists Sarasota Cattlemen

Sarasota, FL

Open and Accepting


University of Chicago Medicine Comprehensive Cancer Center

Chicago, IL

Open and Accepting


National Institutes of Health (Bethesda)

Bethesda, MD

Open and Accepting

New York

Memorial Sloan Kettering Cancer Center

New York, NY

Open and Accepting




MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting


Swedish Cancer Institute - Cherry Hill Campus

Seattle, WA

Open and Accepting
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