a study of azd0486 in subjects with b-cell non-hodgkin lymphoma

Conditions: B-cell Non Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; High-grade B-cell Lymphoma; Follicular Lymphoma

Summary: this phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of azd0486, a cd19 x cd3 t-cell engaging bispecific antibody, in subjects with b-cell non-hodgkin lymphoma (b-nhl).

this dose escalation and optimization study, is evaluating the safety, tolerability, pk, pd and clinical activity of azd0486 monotherapy.

Eligibility criteria:
inclusion criteria: * biopsy proven b-nhl, including dlbcl, hgbl, or fl. * relapsed/refractory cohorts: in order to be eligible subjects must have received at least 2 prior lines of therapy and not be candidates for treatment regimens known to provide clinical benefit in b-nhl. car t-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to car t cell therapies. * 1l fl cohorts: subject has biopsy-proven fl grade 1-3a per who 2016 classification, stage ii-iv, fl international prognostic index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on gelf criteria. radiation to localized disease prior to study entry is allowed if \>14 days from first dose. * all cohorts: subject has an eastern cooperative oncology group (ecog) performance status of ≤ 2. * subject must have adequate liver, bone marrow and kidney function (egfr ≥ 50 ml/min). * subject must have locally confirmed cd19 positivity (must be documented after time of progression from last cd19-targeted therapy, if received) * subject must have at least 1 measurable disease site * subject must have anc \>/= 1000/mm3, platelets \>/= 50,000 mm3, hemoglobin \>/= 8.0 g/dl. transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening * subject must have a total bilirubin \<1.5x uln, ast/alt \< 3xuln exclusion criteria: * subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen. * subject has active central nervous system (cns) involvement by their b-nhl. --subjects may be eligible with a distant history of cns involvement that has been adequately treated with no evidence of recurrence within last 6 months from screening. * subject has a history of leukemic presentation of their b-nhl (\>5,000 circulating lymphoma cells/ul in the peripheral blood). * subject has history or presence of clinically significant cns pathology * subject has cns involvement from active or history of autoimmune disease. * subject received cd19 car t therapy within 3 months prior to first dose. * subject experienced grade ≥ 3 cytokine release syndrome (crs) following prior t-cell engager (tce) or car t-cell therapy. * subject experienced grade ≥ 2 neurotoxicity/immune effector cell-associated neurotoxicity syndrome (icans) following prior tce or car t-cell therapy. * subject has received a peripheral autologous stem cell transplant (sct) within 12 weeks, or an allogeneic sct within 1 year of the first dose of study drug treatment or has received an sct and requires ongoing immunosuppressive therapy. * subjects with human immunodeficiency virus (hiv) infection, or subjects with chronic or active infection with hepatitis b virus (hbv) or hepatitis c virus (hcv). hiv-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. subjects with chronic hbv may be enrolled if the hbv viral load is undetectable on suppressive therapy, or if the subject has a documented cure. subjects with hcv who have a documented cure may be enrolled. * subject has a history of major cardiac abnormalities. * if female, subject must not be pregnant or breastfeeding.

Keywords: nhl dlbcl hgbl cd19 fl