A Study of TNB-486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Number of subjects with Dose-limiting toxicities (DLT) [28 days]
- Number of subjects with adverse events (AEs) and/or serious adverse events (SAEs) [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.
- Maximum Observed Plasma Concentration of TNB-486 (Cmax) [4 weeks]
- Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) [4 weeks]
- Apparent terminal half-life (t1/2) of TNB-486 [From screening until 90 Days after end of treatment]
Secondary Outcome Measures
- Anti-Lymphoma Activity by Objective Response Rate (ORR) [48 months]
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) [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
- Anti-Lymphoma Activity by Duration of Objective Response (DOR) [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
- Anti-Lymphoma Activity by Clinical Benefit Rate [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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Biopsy proven B-NHL, including DLBCL, HGBL, mantle cell lymphoma (MCL) or FL.
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For Arm B Only: Subject has biopsy proven DLBCL or HGBL
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For Arm C only: Subject has biopsy proven FL
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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.
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Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
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Subject must have adequate liver, bone marrow and kidney function (eGFR ≥ 50 mL/min).
Exclusion Criteria:
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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.
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Subject has a history of central nervous system (CNS) involvement by their B-NHL
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Subject has a history of leukemic presentation of their B-NHL, with the exception of MCL.
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Subject has clinically significant CNS pathology
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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.
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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.
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Subject has a history of major cardiac abnormalities.
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If female, subject must not be pregnant or breastfeeding.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Moffitt Cancer Center | Tampa | Florida | United States | 33612 |
| 2 | Norton Cancer Institute | Louisville | Kentucky | United States | 40207 |
| 3 | Levine Cancer Institute/Atrium Health Charlotte NC | Charlotte | North Carolina | United States | 28204 |
| 4 | UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | United States | 15232 |
| 5 | The University of Texas MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 6 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
| 7 | Severance hospital, Yonsei University | Seoul | Korea, Republic of | 3722 | |
| 8 | Asan Medical Center | Seoul | Korea, Republic of | 5505 | |
| 9 | Seoul St Mary's Hospital | Seoul | Korea, Republic of | 6591 |
Sponsors and Collaborators
- TeneoTwo Inc.
Investigators
- Study Chair: Ben Buelow, MD, PhD, TeneoTwo Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TNB486.001