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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04594642
Recruitment Status : Recruiting
First Posted : October 20, 2020
Last Update Posted : October 19, 2022
Sponsor:
Information provided by (Responsible Party):
TeneoTwo Inc.

Brief Summary:
This is a phase 1, open-label study evaluating the safety, tolerability, pharmacokinetic, pharmacodynamic, 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.

Condition or disease Intervention/treatment Phase
B-cell Non Hodgkin Lymphoma Diffuse Large B Cell Lymphoma High-grade B-cell Lymphoma Follicular Lymphoma Drug: TNB-486 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 116 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, 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
Actual Study Start Date : March 2, 2021
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : May 2024


Arm Intervention/treatment
Experimental: Dose Escalation
Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.
Drug: TNB-486
TNB-486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells.

Experimental: Dose Expansion in Subjects with DLBCL or HGBL
An expansion cohort in subjects with DLBCL or HGBL will be enrolled after RP2D is established.
Drug: TNB-486
TNB-486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells.

Experimental: Dose Expansion in Subjects with FL
An expansion cohort in subjects with FL will be enrolled after RP2D is established.
Drug: TNB-486
TNB-486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells.




Primary Outcome Measures :
  1. Number of subjects with Dose-limiting toxicities (DLT) [ Time Frame: 28 days ]
  2. Number of subjects with adverse events (AEs) and/or serious adverse events (SAEs) [ Time Frame: From screening until 90 Days after end of treatment ]
    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.

  3. Maximum Observed Plasma Concentration of TNB-486 (Cmax) [ Time Frame: 4 weeks ]
  4. Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) [ Time Frame: 4 weeks ]
  5. Apparent terminal half-life (t1/2) of TNB-486 [ Time Frame: From screening until 90 Days after end of treatment ]

Secondary Outcome Measures :
  1. Anti-Lymphoma Activity by Objective Response Rate (ORR) [ Time Frame: 48 months ]
    Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment

  2. Anti-Lymphoma Activity by Progression-Free Survival (PFS) [ Time Frame: 48 months ]
    Progression-free survival time is defined as the time from the first dose of TNB-486 to progression or death, whichever occurs first

  3. Anti-Lymphoma Activity by Duration of Objective Response (DOR) [ Time Frame: 48 months ]
    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

  4. Anti-Lymphoma Activity by Clinical Benefit Rate [ Time Frame: 48 months ]
    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



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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).

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04594642


Contacts
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Contact: Ben Buelow, MD, PhD (650) 955-6865 studydirector@ancorabiotech.com

Locations
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United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33612
United States, Kentucky
Norton Cancer Institute Recruiting
Louisville, Kentucky, United States, 40207
United States, North Carolina
Levine Cancer Institute/Atrium Health Charlotte NC Recruiting
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
UPMC Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Korea, Republic of
Severance hospital, Yonsei University Recruiting
Seoul, Korea, Republic of, 3722
Asan Medical Center Recruiting
Seoul, Korea, Republic of, 5505
Seoul St Mary's Hospital Recruiting
Seoul, Korea, Republic of, 6591
Sponsors and Collaborators
TeneoTwo Inc.
Investigators
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Study Chair: Ben Buelow, MD, PhD TeneoTwo Inc.
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Responsible Party: TeneoTwo Inc.
ClinicalTrials.gov Identifier: NCT04594642    
Other Study ID Numbers: TNB486.001
First Posted: October 20, 2020    Key Record Dates
Last Update Posted: October 19, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by TeneoTwo Inc.:
NHL
DLBCL
HGBL
CD19
FL
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases