The TACTIC-19 trial (NCT03880279), set to begin in a few months, comes after the U.S Food and Drug Administration (FDA) and Health Canada cleared the company’s investigational new drug (IND) and clinical trial applications.
“Obtaining FDA and Health Canada clearance of our first IND for this novel approach fulfills our goal to be a clinical stage biotechnology company and demonstrates our commitment to bringing this innovative treatment to patients,” Paul Lammers, MD, president and CEO of Triumvira, said in a press release.
“TAC01-CD19 will be tested at five leading lymphoma clinical study centers in the U.S. and Canada. Based on its preclinical profile, TAC01-CD19 has the potential to represent a significant advancement in T cell therapy,” he added.
TAC01-CD19 was manufactured using Triumvira’s novel T cell Antigen Coupler (TAC) technology, which has the potential to maintain the effectiveness of approved CAR T-cell therapies, while reducing the associated side effects.
T-cells are the immune cells that naturally clear the body from abnormal and tumor cells. However, the T-cells of cancer patients fail to recognize the tumor, which leads to disease progression.
T-cell therapies, such as CAR T-cell therapy, involve collecting the patient’s T-cells and modifying them in the lab to target proteins present in tumor cells. In the case of CAR-T, the modified T-cells carry a chimeric antigen receptor or CAR, that is created in the laboratory.
CAR-T cell therapies have been approved for lymphoma and leukemia, and many are being developed for other types of cancer. However, the chimeric receptor sometimes has deficient control mechanisms and is activated in an uncontrolled way, or without the need to interact with the cancer cell, which leads to toxicity. That’s why researchers are seeking to create safer T-cell therapies.
Triumvira’s TAC technology modifies the T-cells to add a molecule called an antigen coupler, a hybrid protein that recognizes the tumor and interacts with the T-cell receptor, helping it to target the tumor cell. The antigen coupler acts as a co-receptor that facilitates ligand recognition but does not trigger the response directly.
Because TAC technology adds a new molecule instead of altering the natural T-cell receptor, the modified cells show an increased response against the tumor while maintaining their natural control mechanisms, reducing side effects such as toxicity. This technology can be used in types of solid and liquid tumors.
TAC01-CD19 if the first treatment candidate using TAC technology. It targets the CD19 protein that is present on the surface of B-cells, including lymphoma cells. Preclinical data showed that TAC01-CD19 cells do not activate abnormally, and specifically target the tumor, leading to cancer elimination with reduced toxicity.
The TACTIC-19 trial is expects to recruit 36 patients with B-cell lymphomas — including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, and high-grade B-cell lymphoma with specific DNA mutations — whose tumors continued to progress despite treatment with an anthracycline and anti-CD20 therapy, and who failed or were ineligible for an autologous stem cell transplant.
It will be conducted in two parts, including a dose escalation part to determine the optimal dose of TAC01-CD19, and an expansion part to continue studying that dose in a larger group of patients. The main goal is to determine treatment toxicity and incidence of adverse events (side effects).