Breakthrough in cancer immunotherapy: Promising therapy for advanced solid tumours

As part of a clinical study, the Early Clinical Trial Unit (ECTU) at NCT/UCC Dresden has tested the cancer immunotherapy IMA401 for the first time in patients with advanced solid tumours

IMA401 is a bispecific T-cell engager (TCER) that specifically links cancer cells with T cells, thereby directly activating the immune system to fight the tumour.

To achieve this, the molecule simultaneously binds to two targets: a protein produced inside tumour cells known as the tumour antigen MAGEA4/8, and a molecule on the surface of the body’s immune cells (CD3).

These immune cells, known as T lymphocytes, are thereby directed specifically to the tumour locations and activated so that they can destroy the cancer cells.

The full results of the study were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) and published simultaneously in the journal Nature Medicine.

Study design and safety outcomes

In the study, 61 patients with advanced tumours that no longer responded to standard treatments received IMA401 as an infusion. In some cases, the drug was administered in combination with the already approved immunotherapy drug Pembrolizumab.

“Our primary objectives were to demonstrate the safety of IMA401 and to determine the optimal dose for further development,” explained study lead Prof. Martin Wermke, director of the NCT/UCC Early Clinical Trial Unit (ECTU) and professor of experimental tumour therapy.

Overall, the treatment was well tolerated. The most common treatment-related side effects were due to the intended activation of the immune system:

• Cytokine release syndrome:
  • Occurred in 38 per cent of patients and was mainly characterised by fever of grade 1 to 2 severity.
• Lymphopenia:
  • Temporary changes in blood counts were observed in 33 per cent of cases.
• Neutropenia:
  • Reversible changes in blood counts were observed in 31 per cent of cases.

Initial anti-tumour activity

The study demonstrated a response to treatment in several tumour types, including lung cancer, melanoma, and neuroendocrine tumours.

However, the largest group of patients consisted of people with head and neck cancers. Within this specific group:

• Significant tumour 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—meaning the period during which the treatment remained effective—was 8.8 months.

“The results of the study represent a significant advancement for our patients, for whom otherwise only very limited chemotherapy options are available in this situation,” Wermke summarised.

Future clinical outlook

A notable aspect of IMA401 is that it enables the use of tumour markers for immunotherapy that are not located on the surface of the tumour cell but are instead found within it. Given its good tolerability, it is possible to combine IMA401 with other immunotherapies.

The research team will soon begin testing IMA401 in combination with a similar TCER targeting a different lung cancer tumour marker, in the hope of achieving even greater effectiveness. The ECTU plans to continue supporting and consistently expanding this area to consolidate its position in the development of novel cancer therapies.