Dresden: Advances in Cancer Immunotherapy

IMA401 is a so-called bispecific T-cell engager (TCER) that specifically links cancer cells to T cells, thereby directly activating the immune system against the tumor. To do this, the molecule binds to two targets simultaneously: a protein produced in the tumor cells, the tumor antigen MAGEA4/8, and a molecule on the surface of the body’s own immune cells (CD3). These immune cells, known as T lymphocytes, are thereby directed to the tumor sites and activated, enabling them to destroy the cancer cells.

In the study now presented, 61 patients with advanced cancer who no longer responded to standard treatments received IMA401 as an infusion at the Carl Gustav Carus University Hospital (UKD), in some cases in combination with the already approved immunotherapy drug pembrolizumab. “Our primary goals were to demonstrate the safety of IMA401 and to determine the optimal dose for further development,” explains study leader Prof. Martin Wermke, head of the Early Clinical Trial Unit (ECTU) at the National Center for Tumor Diseases (NCT / UCC) and professor of experimental tumor therapy.

Overall, the treatment proved to be well tolerated: The most common treatment-related side effects were due to the desired activation of the immune system. The study showed a response to treatment in several tumor types, including lung cancer, melanoma, and neuroendocrine tumors. However, the largest patient group consisted of people with head and neck tumors. Here, a significant tumor shrinkage was observed in four out of 14 patients treated within the optimal dose range. In three of these four individuals, the response was still ongoing at the time of analysis. The median duration of response—that is, the treatment’s efficacy—was 8.8 months.

“The study results represent significant progress for our patients, who would otherwise only be offered chemotherapy with very limited efficacy in this situation,” says Martin Wermke, summarizing the findings. “What is particularly exciting is that IMA401 makes it possible to utilize tumor markers for immunotherapy that are not located on the surface of the tumor cell but are instead found within its interior. Due to its good tolerability, there is the possibility of combining IMA401 with other immunotherapies. We will soon be testing IMA401 with a similar TCER targeting a different tumor marker in lung cancer. We hope this will result in even greater efficacy.”

• The Early Clinical Trial Unit (ECTU)

The Early Clinical Trial Unit (ECTU) at NCT / UCC Dresden specializes in conducting early-phase clinical trials. “We see our ECTU as an opportunity to make new cancer therapies available to patients in the region early on and as safely as possible. The recently published study on IMA401 is a particularly prominent example of the effectiveness of this approach,” says Prof. Martin Bornhäuser, one of the managing directors of the NCT / UCC Dresden and director of Medical Clinic I at the UKD, with satisfaction.