TDT-3

Table of contents

• What is TDT-3?
• How does TDT-3 work?
• Which conditions is TDT-3 studied for?
• How is TDT-3 given?
• What do the clinical trials show?
• What side effects are known?

What is TDT-3?

TDT-3 is an investigational cell therapy being developed for the treatment of certain blood cancers. It is a type of autologous TCR T-cell therapy, meaning it is made from a patient's own immune cells (T cells) that are collected, modified in a laboratory, and then given back to the same patient.^[1] The substance is classified in the registry as a structurally diverse substance of cell therapy origin and has no marketing authorisation in the product records, confirming its status as an investigational medicine.^[1] The product is supplied by Oslo University Hospital.^[1]

How does TDT-3 work?

TDT-3 is designed to target a protein called TdT (terminal deoxynucleotidyl transferase), which is found on the surface of certain leukemia and lymphoma cells. The patient's T cells are engineered to recognise and attack cells that carry this TdT protein.^[1] The therapy is restricted to patients whose immune system type is HLA-A*02:01 positive, because the engineered T cells recognise the TdT protein only when it is presented by this specific immune marker.^[1]

Which conditions is TDT-3 studied for?

• Acute lymphoblastic leukemia (ALL) — a fast-growing cancer of the blood and bone marrow that affects white blood cells called lymphocytes.
• Lymphoblastic lymphoma (LBL) — a rare type of non-Hodgkin lymphoma that closely resembles ALL and affects lymphocytes in the lymph nodes and other tissues.

In the current trial, patients must have relapsed or refractory disease, meaning the cancer has returned after previous treatment or has not responded to standard therapy.^[1]

How is TDT-3 given?

TDT-3 is given as a dispersion for infusion, administered directly into the bloodstream through a vein (intravenous infusion).^[1] The trial tests two forms of the product: a weight-based dose and a non-weight-based dose.^[1] Before receiving TDT-3, patients in the trial receive a conditioning regimen of fludarabine and cyclophosphamide, which are chemotherapy drugs used to prepare the body for the cell therapy.^[1]

What do the clinical trials show?

There is one authorised clinical trial of TDT-3 in the EU registry. It is a Phase 1/2 study, which means it is an early-stage trial that first tests safety and dosing in a small number of patients, then begins to look at whether the therapy has biological activity.^[1] The trial plans to enroll 15 participants aged 1 year and older.^[1]

The trial measures several outcomes. The primary outcomes focus on safety and feasibility: the type, incidence, and severity of dose-limiting toxicities during the first 28 days after infusion; the incidence and severity of adverse events; the maximum tolerated dose; and the rate of successful manufacture and delivery of TDT-3 within a clinically relevant time frame.^[1] The study also aims to determine a preliminary recommended Phase 2 dose.^[1]

As this is an ongoing early-phase trial, no efficacy results are available yet. The trial is currently in the authorised status, meaning it has received regulatory approval to proceed but has not yet reported results.^[1]

What side effects are known?

Because TDT-3 is an investigational therapy in an early-phase trial, its side effect profile is not yet fully established. The trial is specifically designed to assess the safety of TDT-3, including the type, incidence, and severity of adverse events and dose-limiting toxicities.^[1] No detailed side effect data from completed studies are available in the provided sources.