Phase 1, Open-label, Dose-escalation and Expansion Study of TNB-486, a Bispecific Antibody Targeting CD19 in Subjects with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma.
Primary:
- Evaluate the safety and tolerability of TNB-486 when administered as monotherapy
- Determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for TNB-486 when administered as monotherapy
- Evaluate the pharmacokinetics (PK) of TNB-486 when administered as monotherapy.
Secondary:
- Evaluate the clinical activity of TNB-486 when administered as monotherapy.
- Evaluate anti-drug antibody titers for TNB-486 when administered as monotherapy
Exploratory:
- Evaluate pharmacodynamic and exploratory biomarkers and assess their association with safety, pharmacokinetics, and clinical activity.
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Matthew Matasar
- Principal Investigator
Inclusion Criteria
- Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
- For Arm B Only: Subject has biopsy proven DLBCL or HGBL
- For Arm C only: Subject has biopsy proven FL
- Subject has received at least 2 lines of therapy to which the subject has been either
refractory or has subsequently relapsed. In order to be eligible for this study
subjects must not be candidates for treatment regimens known to provide clinical
benefit in B-NHL.
- 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 a history of central nervous system (CNS) involvement by their B-NHL
- Subject has a history of leukemic presentation of their B-NHL.
- Subject has history or presence of clinically significant CNS pathology
- Subject has CNS involvement from active or history of autoimmune disease.
- 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.
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.