Clinical Trials /

A Study of TNB-486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

NCT04594642

Description:

This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) who have received 2 or more prior lines of therapy. The study consists of 3 parts, a monotherapy dose escalation (Arm A), a monotherapy dose expansion in subjects with diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL) (Arm B), and a monotherapy dose expansion in subjects with follicular lymphoma (FL) (Arm C). Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified in Arm A, Arm B and Arm C will be initiated to further characterize the safety, tolerability and pharmacokinetic (PK) profile of the MTD/RP2D dose of TNB-486 monotherapy in subsets of subjects with DLBCL/HGBL or FL.

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Richter Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of TNB-486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
  • Official Title: A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of TNB-486, a Bispecific Antibody, in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: TNB486.001
  • NCT ID: NCT04594642

Conditions

  • B-cell Non Hodgkin Lymphoma
  • Diffuse Large B Cell Lymphoma
  • High-grade B-cell Lymphoma
  • Follicular Lymphoma

Interventions

DrugSynonymsArms
TNB-486Dose Escalation

Purpose

This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of TNB-486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) who have received 2 or more prior lines of therapy. The study consists of 3 parts, a monotherapy dose escalation (Arm A), a monotherapy dose expansion in subjects with diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL) (Arm B), and a monotherapy dose expansion in subjects with follicular lymphoma (FL) (Arm C). Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified in Arm A, Arm B and Arm C will be initiated to further characterize the safety, tolerability and pharmacokinetic (PK) profile of the MTD/RP2D dose of TNB-486 monotherapy in subsets of subjects with DLBCL/HGBL or FL.

Trial Arms

NameTypeDescriptionInterventions
Dose EscalationExperimentalSequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.
  • TNB-486
Dose Expansion in Subjects with DLBCL or HGBLExperimentalAn expansion cohort in subjects with DLBCL or HGBL will be enrolled after RP2D is established.
  • TNB-486
Dose Expansion in Subjects with FLExperimentalAn expansion cohort in subjects with FL will be enrolled after RP2D is established.
  • TNB-486

Eligibility Criteria

        Inclusion Criteria:

          -  Biopsy proven B-NHL, including DLBCL, HGBL, transformed indolent NHL including
             Richter's transformation, mantle cell lymphoma (MCL), FL, or marginal zone lymphoma
             (MZL).

          -  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).

        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, with the exception of
             MCL or MZL.

          -  Subject has clinically significant CNS pathology

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of subjects with Dose-limiting toxicities (DLT)
Time Frame:28 days
Safety Issue:
Description:The incidence, timing, seriousness, and relationship to study treatments of adverse events will be evaluated. An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect.

Secondary Outcome Measures

Measure:Anti-Lymphoma Activity by Objective Response Rate (ORR)
Time Frame:48 months
Safety Issue:
Description:Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
Measure:Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Time Frame:48 months
Safety Issue:
Description:Progression-free survival time is defined as the time from the first dose of TNB-486 to progression or death, whichever occurs first
Measure:Anti-Lymphoma Activity by Duration of Objective Response (DOR)
Time Frame:48 months
Safety Issue:
Description:The duration of objective response for a subject is defined as the time from the initial objective response to disease progression or death, whichever occurs first
Measure:Anti-Lymphoma Activity by Clinical Benefit Rate
Time Frame:48 months
Safety Issue:
Description:Clinical benefit rate is defined as the proportion of subjects with a confirmed complete response, partial response or minor response, or stable disease for at least 24 weeks after responding to treatment

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Teneobio, Inc.

Trial Keywords

  • NHL
  • DLBCL
  • HGBL
  • CD19
  • FL

Last Updated

October 13, 2020