Back to resultsA Study of TNB-486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Primary Purpose
B-cell Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma
Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
TNB-486
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Non Hodgkin Lymphoma focused on measuring NHL, DLBCL, HGBL, CD19, FL
Eligibility 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.
Sites / Locations
- Moffitt Cancer CenterRecruiting
- Norton Cancer InstituteRecruiting
- Levine Cancer Institute/Atrium Health Charlotte NCRecruiting
- UPMC Hillman Cancer CenterRecruiting
- The University of Texas MD Anderson Cancer CenterRecruiting
- Medical College of WisconsinRecruiting
- Severance hospital, Yonsei UniversityRecruiting
- Asan Medical CenterRecruiting
- Seoul St Mary's HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Dose Escalation
Dose Expansion in Subjects with DLBCL or HGBL
Dose Expansion in Subjects with FL
Arm Description
Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.
An expansion cohort in subjects with DLBCL or HGBL will be enrolled after RP2D is established.
An expansion cohort in subjects with FL will be enrolled after RP2D is established.
Outcomes
Primary Outcome Measures
Number of subjects with Dose-limiting toxicities (DLT)
Number of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
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.
Maximum Observed Plasma Concentration of TNB-486 (Cmax)
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
Apparent terminal half-life (t1/2) of TNB-486
Secondary Outcome Measures
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Progression-free survival time is defined as the time from the first dose of TNB-486 to progression or death, whichever occurs first
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
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
Anti-Lymphoma Activity by Clinical Benefit Rate
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04594642
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 Targeting CD19 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 2, 2021 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
May 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TeneoTwo Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Follicular Lymphoma
Keywords
NHL, DLBCL, HGBL, CD19, FL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
116 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dose Escalation
Arm Type
Experimental
Arm Description
Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.
Arm Title
Dose Expansion in Subjects with DLBCL or HGBL
Arm Type
Experimental
Arm Description
An expansion cohort in subjects with DLBCL or HGBL will be enrolled after RP2D is established.
Arm Title
Dose Expansion in Subjects with FL
Arm Type
Experimental
Arm Description
An expansion cohort in subjects with FL will be enrolled after RP2D is established.
Intervention Type
Drug
Intervention Name(s)
TNB-486
Intervention Description
TNB-486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells.
Primary Outcome Measure Information:
Title
Number of subjects with Dose-limiting toxicities (DLT)
Time Frame
28 days
Title
Number of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
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.
Time Frame
From screening until 90 Days after end of treatment
Title
Maximum Observed Plasma Concentration of TNB-486 (Cmax)
Time Frame
4 weeks
Title
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
Title
Apparent terminal half-life (t1/2) of TNB-486
Time Frame
From screening until 90 Days after end of treatment
Secondary Outcome Measure Information:
Title
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Description
Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
Time Frame
48 months
Title
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Description
Progression-free survival time is defined as the time from the first dose of TNB-486 to progression or death, whichever occurs first
Time Frame
48 months
Title
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
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
Time Frame
48 months
Title
Anti-Lymphoma Activity by Clinical Benefit Rate
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
Time Frame
48 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ben Buelow, MD, PhD
Phone
(650) 955-6865
Email
studydirector@ancorabiotech.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ben Buelow, MD, PhD
Organizational Affiliation
TeneoTwo Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Name
Norton Cancer Institute
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40207
Country
United States
Individual Site Status
Recruiting
Facility Name
Levine Cancer Institute/Atrium Health Charlotte NC
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Individual Site Status
Recruiting
Facility Name
UPMC Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Recruiting
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Name
Severance hospital, Yonsei University
City
Seoul
ZIP/Postal Code
3722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
5505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul St Mary's Hospital
City
Seoul
ZIP/Postal Code
6591
Country
Korea, Republic of
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study of TNB-486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
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