Evaluating NX-2127 for adults with advanced B-cell cancers

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

This study is testing a new treatment called NX-2127 to see if it can help adults with advanced B-cell cancers feel better and fight their disease.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 248 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Nurix Therapeutics, Inc. (Industry-sponsored)
• Drugs / interventions: radiation, prednisone
• Locations: 16 sites (Duarte, California and 15 other locations)
• Trial ID: NCT04830137 on ClinicalTrials.gov

What this trial studies

This Phase 1a/1b multicenter, open-label study aims to assess the safety and anti-cancer activity of NX-2127 in adults with relapsed or refractory B-cell malignancies. The study consists of two phases: Phase 1a focuses on dose escalation to determine safety and tolerability, while Phase 1b will optimize the dosage based on findings from Phase 1a. Participants will be enrolled based on specific B-cell malignancy indications and will receive NX-2127, with random assignment to different dose levels in the second stage of Phase 1b.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with relapsed or refractory B-cell malignancies who have received at least two prior systemic therapies.

Not a fit: Patients with certain aggressive forms of lymphoma or specific genetic mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced B-cell malignancies who have limited treatment alternatives.

How similar studies have performed: While this approach is novel, similar studies targeting B-cell malignancies have shown promise, indicating potential for success.

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 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)

Exclusion Criteria:

* 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. Exception: patients with non-metastatic, non-melanoma skin cancer are eligible
* 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 (for 2 days) or moderate inducers of CYP3A for 7 days

Where this trial is running

Duarte, California and 15 other locations

• City of Hope — Duarte, California, United States (Recruiting)
• University of California Irvine — Orange, California, United States (Completed)
• University of California San Francisco Medical Center — San Francisco, California, United States (Completed)
• Sarah Cannon Research Institute at Colorado Blood Cancer Institute — Denver, Colorado, United States (Recruiting)
• Mount Sinai Comprehensive Cancer Center — Miami Beach, Florida, United States (Completed)
• Sarah Cannon Research Institute at Florida Cancer Specialists — Sarasota, Florida, United States (Completed)
• The University of Chicago Medical Center — Chicago, Illinois, United States (Recruiting)
• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Completed)
• University of Cincinnati Medical Center — Cincinnati, Ohio, United States (Completed)
• OSU Wexner Medical Center — Columbus, Ohio, United States (Completed)
• Tennessee Oncology — Nashville, Tennessee, United States (Recruiting)
• Baylor University Medical Center — Dallas, Texas, United States (Completed)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• Huntsman Cancer Institute, University of Utah — Salt Lake City, Utah, United States (Recruiting)
• Swedish Cancer Institute — Seattle, Washington, United States (Completed)

Study contacts

• Study coordinator: Patient Outreach

Conditions Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Waldenstrom Macroglobulinemia; Mantle Cell Lymphoma; Marginal Zone Lymphoma; Follicular Lymphoma; Diffuse Large B-cell Lymphoma; Primary Central Nervous System Lymphoma