TAK-169 targets the CD38 protein that is found in high levels on the surface of myeloma cells. The U.S. Food and Drug Administration accepted an investigational new drug application for TAK-169 in June 2019.
How does TAK-169 work?
TAK-169 is an engineered toxin body, which contains the CD38-specific antibody fragment fused to a Shiga-like toxin A-subunit (SLTA), a bacterial protein that can inhibit irreversibly the protein-making machinery of cells. The bioengineered CD38-specific antibody binds to the CD38 molecule and gets taken into the malignant myeloma cells. Once inside, the SLTA protein binds to a cellular component called the ribosome, thereby blocking protein synthesis. This is thought to induce cell death and hence lead to the death of myeloma cells. The SLTA protein is bioengineered in such a way that it escapes being recognized by the immune system.
TAK-169 in clinical trials
Preliminary preclinical results about TAK-169 were presented at the American Association for Cancer Research meeting in 2019. According to researchers, in vitro experiments in several myeloma cell lines demonstrated that TAK-169 is highly toxic for cells. Moreover, TAK-169 was effective in killing patient-derived myeloma cells that have been previously exposed to Darzalex (daratumumab), a CD38 inhibitor. Under-the-skin injections of TAK-169 showed regression of myeloma in several myeloma xenograft models. TAK-169 was well-tolerated at doses expected to be efficacious in humans when it was repeatedly injected at regular intervals in non-human primates.
These promising results led to the planning of a Phase 1 clinical trial (NCT04017130) to assess the safety, tolerability, pharmacokinetics (movement in the body), pharmacodynamics (effect on the body), and efficacy of TAK-169 in patients with relapsed or refractory multiple myeloma (RRMM).
The study will be conducted in two phases: a dose-escalation phase (part 1) and an expansion phase (part 2).
In part 1, the first group of patients will receive 50 ug/kg of TAK-169 on days 1, 8, 15, and 22 in a 28-day treatment cycle. Then, the safety, pharmacokinetics, pharmacodynamics, and efficacy data will be analyzed and based on these, subsequent groups will receive 100, 200, 335, 500, and 665 ug/kg of TAK-169, once weekly. Based on preliminary data, TAK-169 may also be administered once every two weeks.
In part 2, the study will evaluate two types of RRMM patient groups: those whose disease failed to respond to or relapsed following Darzalex treatment and those who have never received anti-CD38 therapy. Patients in the Darzalex group will receive TAK-169 once a week or once every two weeks while the group that has never received anti-CD38 therapy will receive the treatment once a week only. The doses for part 2 will be decided after analyzing data from part 1.
This study is expected to last 34 months, and patients will be followed up for 30 days after the last dose has been administered.
The trial is now recruiting patients for part 1 of the trial at a location in Florida and Minnesota. It aims to enroll between 39 to 60 participants in part 1 and around 54 participants in part 2. The study is estimated to complete in January 2023.
Last updated: Jan. 24, 2020
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