TLN-121 in Relapsed or Refractory Non-Hodgkin Lymphomas

Official title

An Open-Label, Multicenter, Phase 1 Trial to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of TLN-121 as a Single Agent and in Combination With Other Anti-Lymphoma Agents, in Patients With Relapsed or Refractory Non-Hodgkin Lymphomas

Overview

The primary purpose of this study is to evaluate the safety, pharmacokinetics,, and preliminary anti-tumor activity of TLN-121 as a single agent and in combination with other anti-lymphoma therapies in patients with relapsed or refractory Non-Hodgkin Lymphomas

Interventions

• Drug TLN-121
  Specified dose on specified days.
• Drug TLN-254
  Specified dose on specified days.
• Drug TLN-121
  Specified dose on specified days.

Primary outcome measures

• Number of participants experiencing adverse events (AEs) that meet protocol-defined dose-limiting toxicity (DLT) criteria following administration of TLN-121 alone or in combination with TLN-254. [Time frame: Up to 2 years]
• Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) [Time frame: Up to 2 years]
• Clinically significant ECG QT Interval from baseline in safety laboratory test results, assessed as per NCI CTCAE v5.0 [Time frame: Up to 2 years]
• Clinically significant laboratory abnormalities from baseline in safety laboratory test results, assessed as per NCI CTCAE v5.0 [Time frame: Up to 2 years]

Secondary outcome measures (7)

• Maximum Observed Plasma Concentration (Cmax) of TLN-121 [Time frame: Up to 2 years]
• Time to Maximum Plasma Concentration (Tmax) of TLN-121 [Time frame: Up to 2 years]
• Minimum Observed Plasma Concentration (Cmin) of TLN-121 [Time frame: Up to 2 years]
• Area Under the Plasma Concentration-Time Curve (AUC) of TLN-121 [Time frame: Up to 2 years]
• Anti-tumor activity of TLN-121 and TLN-121 in combination with TLN-254 by evaluating the objective response rate (ORR) according to the Lugano response criteria for Non-Hodgkin Lymphoma [Time frame: Up to 2 years]
• Anti-tumor activity of TLN-121 and TLN-121 in combination with TLN-254 by evaluating the complete response rate (CR) according to the Lugano response criteria for Non-Hodgkin Lymphoma [Time frame: Up to 2 years.]
• Anti-tumor activity of TLN-121 and TLN-121 in combination with TLN-254 by evaluating the duration of response (DOR) as assessed by the time from the date of first objective response to the date of disease progression [Time frame: Up to 2 years]

Eligibility criteria

Inclusion criteria

Disease Characteristics

• Participant must have measurable disease at study entry
• Participants must have one of the following histologically documented hematologic malignancies:

• Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (DLBCL, NOS), Follicular lymphoma (FL) grade 3b, or transformed lymphoma from FL following at least 2 prior lines of therapy.
• FL grade 1-3a that requires treatment following at least 2 prior lines of therapy.
• The following Peripheral T-cell lymphoma (PTCL) subtypes that have relapsed after, or not responded to at least 1 prior systemic treatment regimen:

• Nodal T-follicular helper (Tfh) cell lymphoma angioimmunoblastic; Follicular helper T-cell lymphoma, angioimmunoblastic type (AITL).
• Nodal Tfh cell lymphoma, follicular type; Follicular helper T-cell lymphoma, follicular type.
• Nodal Tfh cell lymphoma, NOS; Follicular helper T-cell lymphoma, NOS.
• High-Grade B-Cell Lymphoma that has relapsed after, or not responded to at least 2 prior systemic treatment regimens.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion criteria

• Participants must not have current central nervous system (CNS) involvement. Participants with past history of CNS involvement of lymphoma must have had CNS disease fully treated with no evidence of recurrence within 12 months.
• Participant must not have a history of autologous stem cell transplantation within 60 days or allogeneic stem cell transplantation within 90 days prior to the start of the study.
• Participant must not have a history of CAR T-cell or other T-cell targeting treatment ≤ 4 weeks prior to the start of the study.
• Participant must not have major surgery or severe trauma within 4 weeks prior to the start of the study.
• Participants must not have any condition, including significant acute or chronic medical illness, active or uncontrolled infection, or the presence of laboratory abnormalities, that places participants at unacceptable risk if participating in this study.
• Pregnant or lactating.
• Conditions that could affect drug absorption.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 8 centers

• Stanford Medicine Cancer Center — Palo Alto
• The START Center for Cancer Care - Midwest — Grand Rapids
• Washington University School of Medicine — St Louis
• Memorial Sloan Kettering Cancer Center — New York
• Weill Cornell Medicine - New York Presbyterian Hospital — New York
• Hospital of the University of Pennsylvania — Philadelphia
• SCRI Oncology Partners — Nashville
• The University of Texas MD Anderson Cancer Center — Houston

Australia · 5 centers

• Macquarie University Hospital — Macquarie Park
• Princess Alexandra Hospital — Woolloongabba
• Cabrini Health — Malvern
• Peter MacCallum Cancer Centre — Melbourne
• Linear Clinical Research — Perth

Canada · 1 center

• BC Cancer - Vancouver — Vancouver

Identifiers

NCT: NCT07082803 · TLN-121-2501

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗