Targeting tumors from the inside
A new class of cancer drug is showing promise against advanced solid tumors. IMA401, a bispecific T-cell engager, works by linking cancer cells to the body's immune T cells. It binds to two targets at once: MAGEA4/8, a protein found inside tumor cells, and CD3 on the surface of T cells, redirecting the immune system to attack the cancer.
The Phase Ia/Ib trial enrolled 61 patients with advanced solid tumors that no longer responded to standard treatments. The study, led by Professor Martin Wermke of the NCT/UCC Early Clinical Trial Unit in Dresden, was presented at the ASCO Annual Meeting on May 31 and published simultaneously in Nature Medicine.
Results in head and neck cancer
Responses were observed across several cancer types, including lung cancer, melanoma, and neuroendocrine tumors. The most promising results came from the head and neck cancer subgroup. Of 14 patients who received the optimal dose, four (about 29%) showed tumor shrinkage. Three of those four had ongoing responses at the time of analysis, with a median response duration of 8.8 months.
The drug was well tolerated. The most common side effects were cytokine release syndrome (38%, mostly mild fever) and temporary drops in white blood cell counts. These effects were linked to the intended activation of the immune system and were manageable.
Expanding the immunotherapy toolkit
Many existing immunotherapies target proteins on the surface of cancer cells. IMA401 is different: it targets an antigen found inside the cell, which is then displayed on the cell surface. This approach opens up a wider range of targets for immunotherapy.
"The results represent a real advance for patients who have very limited chemotherapy options," Wermke said. The team plans to test IMA401 in combination with a second T-cell engager targeting a different tumor marker in lung cancer. A larger Phase II trial is being designed.