As part of Gustave Roussy's new 2030 institutional strategic project, the INNOCARE programme integrates clinical, fundamental and translational research, with the aim of better understanding the mechanisms of action of innovative drugs, in order to improve their efficacy and better identify the patients who can benefit from them.
Antibodies coupled to anticancer drugs, or ADCs, are a new class of drugs designed as targeted therapies to treat cancers. The first generation of these complex molecules was developed in the 1980s, and it is only in recent years that the development of new technologies has led to a3rd generation of ADCs, less toxic and more selective to the tumor.
Guiding chemotherapy directly into the tumor
ADCs consist of an antibody linked to a biologically active anti-cancer drug. They are designed to specifically target receptors on the surface of tumor cells. By attaching to the tumor, the antibody delivers a dose of chemotherapy directly into the cancer cell to destroy it. Their mechanism of action is different from chemotherapy alone, since ADCs deliver the cytotoxic drug directly to tumour cells, while preserving the majority of healthy cells. As a result, the dose and efficacy delivered to cancer cells is increased, and side effects are reduced.
ICARUS: two clinical trials on two of the most common cancers
As part of INNOCARE, the ICARUS programme aims to understand the mechanisms of action of 2 ADCs, patritumab-deruxtecan and datopotomab-deruxtecan, in order to improve their efficacy and better identify patients who will derive the greatest benefit from these drugs. Two multicenter Phase II clinical trials, entitled ICARUS-LUNG01 and ICARUS-BREAST0,1 are currently underway for patients with metastatic lung or breast cancer.
Understanding how these drugs also activate the immune system
ADCs have a complex mechanism of action, acting in several stages. One of the aims of the study is to better understand how these drugs promote the recruitment of immune cells.
The researchers are also studying which factors allow or prevent ADCs from entering tumour cells. The aim is to identify patients who do or do not express these factors, and who will respond differently to therapy.
They are also interested in the factors that promote the disruption of the link between the antibody and the chemotherapy drug, or conversely, that inhibit it.
Mechanisms and factors favoring the recruitment of immune cells are also at the heart of their research in this project.
Combining conjugated antibodies with other treatments: a new hope
Based on cross-disciplinary research, the teams also aim to identify predisposition, sensitivity and resistance factors to treatment with these molecules. In this way, the program should make it possible to propose the most effective therapeutic combinations combining ADCs with other treatments: targeted therapies, hormone therapy or immunotherapy. These therapeutic combinations will be evaluated in clinical trials.
