What's the purpose of this trial?
This is a first-in-human dose escalation and cohort expansion multicenter, open-label study designed to evaluate the safety and preliminary efficacy of NX-5948 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
* Patients must be ≥18 years of age.
* Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, DLBCL, FL, MCL, MZL, or WM.
* Patients in Phase 1a must meet the following:
o Received at least 2 prior systemic therapies (or at least 1 prior therapy for WM) and have no other therapies known to provide clinical benefit.
* Patients in Phase 1b (Cohort Expansion) must have histologically documented R/R CLL, SLL, DLBCL, FL, MCL, MZL, WM, PCNSL or any of these indications with CNS involvement.
* Patients in Phase 1b (Cohort Expansion) must meet criteria for systemic treatment and must have failed 2 prior lines of therapy (or at least 1 prior line of therapy for patients with WM, PCNSL, or secondary CNS involvement).
* Patients must have radiographically measurable disease per response criteria specific to the malignancy. Evaluable disease in bone marrow or other compartments is also allowed. Target lymph nodes must be \> 1.5 cm and extranodal lesions must be ≥ 1.0 cm in longest diameter. Other quantifiable disease (such as bone marrow infiltration, minimal residual disease, splenic enlargement) is also allowed.
* ECOG performance status of 0 or 1.
* Adequate organ and bone marrow function, in the absence of growth factors and without platelet transfusions as defined by lab parameters
Key Exclusion Criteria:
* Prior treatment for the indication under study for anti-cancer intent that includes:
1. Radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation).
2. Prior systemic chemotherapy within 4 weeks of planned start of study drug. Note: Use of intrathecal chemotherapy is allowed per Institutional guidelines.
3. Prior monoclonal antibody therapy within 4 weeks of planned start of study drug.
4. Prior small molecule therapy within 4 weeks or 5 half-lives (whichever is shorter) of planned start of study drug.
5. Autologous or allogeneic stem cell transplant within 100 days prior to planned start of study drug.
6. Chimeric antigen receptor T-cell (CAR-T) therapy within 100 days prior to start of study drug (within 30 days prior to start of study drug for Phase 1b). Must have evidence of B-cell recovery if patient received prior CAR-T therapy.
7. Use of systemic corticosteroids outside of dosing limits described below and within the 14 days prior to initiation of study treatment excepting those used as prophylaxis for radio diagnostic contrast. Patients with CNSL: no greater than 40 mg/day prednisone, or equivalent, CNSL patients using greater than 20 mg/day prednisone, or equivalent must be clinically stable at that dose for 14 days. All other diagnoses: no greater than 20 mg/day prednisone or equivalent.
8. Use of immunosuppressive drugs other than systemic corticosteroids within 30 days prior to first dose of study drug
* Active, uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia.
* Patient has any of the following:
1. Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, or placement of a coronary arterial stent within 6 months of planned start of study drug.
2. Uncontrolled atrial fibrillation or other clinically significant arrhythmias, conduction abnormalities, or New York Heart Association (NYHA) class III or IV heart failure within 6 months of planned start of study drug.
3. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage within 6 months of planned start of study drug.
4. Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, severe congenital heart disease, or persistent uncontrolled hypertension defined as systolic blood pressure \> 160 mmHg or diastolic blood pressure \> 100 mmHg despite optimal medical management) within 6 months of planned start of study drug.
* Bleeding diathesis, or other known risk for acute blood loss.
* History of Grade ≥ 2 hemorrhage within 28 days of planned start of study drug.
Additional Trial Information
Enrollment: 130 patients (estimated)