A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies
Study Details - NCT05131022
Diffuse Large B Cell Lymphoma (DLBCL)
Chronic Lymphocytic Leukemia (CLL)
Small Lymphocytic Lymphoma (SLL)
Follicular Lymphoma (FL)
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This is a first-in-human Phase 1a/1b multicenter, open-label study designed to evaluate the safety and anti-cancer activity of NX-5948 in patients with advanced B-cell malignancies.
Phase 1a is a dose escalation to evaluate the safety and tolerability of NX-5948 in adult patients with relapsed/refractory (R/R) B cell malignancies who have received at least 2 prior lines of therapy and for whom no other therapies are known to provide clinical benefit. Indications include: Chronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), non-germinal center B-cell subtype (non-GCB) Diffuse Large B-cell Lymphoma (DLBCL), Mantle Cell Lymphoma (MCL), Waldenstrom Macroglobulinemia (WM), Marginal Zone Lymphoma (MZL), Follicular Lymphoma (FL) including those with secondary CNS involvement in any disease indication listed, or Primary Central Nervous System Lymphoma (PCNSL).
Phase 1b will investigate the efficacy of NX-5948 at the dose(s) selected in Phase 1a in up to 4 cohorts of patients with histologically confirmed R/R B-cell malignancy indications who have received at least 2 prior lines of therapy (or at least 1 prior line for patients with WM or PCNSL):
CLL or SLL including those with secondary CNS involvement of their disease
Non-GCB DLBCL or MCL including those with secondary CNS involvement of their disease
MZL, WM, or FL including those with secondary CNS involvement of their disease
Phase: Phase 1
Clinical Trial ID: NCT05131022
Inclusion Criteria »
Exclusion Criteria »
Key Inclusion Criteria:
Age ≥18 years
Patients in Phase 1a (Dose Escalation) must have histologically confirmed R/R CLL, SLL, non-GCB DLBCL, Richter-transformed DLBCL, high-grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangements, high-grade B-cell lymphomas NOS, FL, MCL, MZL (EMZL, MALT, NMZL, SMZL), or WM, including those with secondary CNS involvement in any disease indication listed or PCNSL.
Patients in Phase 1a must meet the following:
o Received at least 2 prior lines of therapy and have no other therapies known to provide clinical benefit.
Patients in Phase 1b (Cohort Expansion) must have 1 of the following histologically documented R/R B-cell malignancies, must meet criteria for systemic treatment, and must have failed 2 prior lines of therapy: CLL or SLL, Non-GCB DLBCL, MCL, FL, MZL, WM, including those with secondary CNS involvement of their disease for all above indications, or PCNSL.
Radiographically measurable disease per response criteria specific to the malignancy. Target lymph nodes must be > 1.5 cm and extranodal lesions must be ≥ 1.0 cm in longest diameter.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0-2 for patients with PCNSL and secondary CNS involvement).
Adequate organ and bone marrow function
Prior treatment for the indication under study for anti-cancer intent that includes:
Radiotherapy within 2 weeks of planned start of study drug (excluding limited palliative radiation).
Prior systemic chemotherapy within 4 weeks of planned start of study drug. Note: Use of intrathecal chemotherapy is allowed per Institutional guidelines.
Prior monoclonal antibody therapy within 4 weeks of planned start of study drug.
Prior small molecule therapy within 4 weeks or 5 half-lives (whichever is shorter) of planned start of study drug.
Autologous or allogeneic stem cell transplant within 100 days prior to planned start of study drug.
Chimeric antigen receptor (CAR) T-cell 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-cell therapy.
Use of systemic corticosteroids outside of dosing limits described below and within 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, central nervous system lymphoma (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.
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 within 6 months of planned start of study drug:
Myocardial infarction, unstable angina, unstable symptomatic ischemic heart disease, or placement of a coronary arterial stent
Uncontrolled atrial fibrillation or other clinically significant arrhythmias, conduction abnormalities, or New York Heart Association (NYHA) class III or IV heart failure
Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events), stroke, or intracranial hemorrhage
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)
Bleeding diathesis, or other known risk for acute blood loss.
History of Grade ≥ 2 hemorrhage within 28 days of planned start of study drug.
11 Study Locations
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