Targeting tissue factor in advanced solid tumours
Mené sur 27 patients atteints d'une tumeur solide de stade localement avancé et/ou métastatique, cet essai de phase I/II évalue les caractéristiques pharmacocinétiques, l'activité antitumorale, la dose maximale tolérée et la toxicité du trisotumab védotin, un conjugué anticorps-médicament ciblant le facteur tissulaire
Despite the development of more effective therapies that modulate antitumour immune responses, target oncogenic mutations, and block key hormonal and cell cycle pathways, outcomes remain poor in many patients with metastatic cancers. Antibody–drug conjugates—which are therapeutics composed of an antibody that targets receptors overexpressed on cancer cells, a cytotoxic agent or payload, and a linker molecule—are an intriguing approach in these settings. Antibody–drug conjugates might offer advantages over both conventional chemotherapy (by permitting delivery of the cytotoxic molecule to the tumour microenvironment, while limiting systemic absorption) and classical antibody-directed therapy (by the addition of a cytotoxic payload). So far, four antibody–drug conjugates have been approved by the US Drug and Food Administration for cancer treatment. Gemtuzumab ozogamicin, an anti-CD33 antibody linked to calicheamicin, is approved for acute myeloid leukaemia. Inotuzumab ozogamicin, an anti-CD22 antibody linked to calicheamicin, is approved for acute lymphoblastic leukaemia. Brentuximab vedotin, an anti-CD30 antibody linked to monomethyl auristatin E (MMAE), is approved for Hodgkin lymphoma (both relapsed refractory and untreated disease in combination with chemotherapy), both systemic and cutaneous anaplastic large cell lymphomas, and CD30-expressing mycosis fungoides. In 2013, ado-traztuzumab emtansine, which is a human epidermal growth factor receptor 2-targeted antibody linked to DM1 (a microtubule inhibitor), was approved for human epidermal growth factor receptor 2-positive metastatic breast cancer, becoming the first antibody–drug conjugate approved for treatment of solid tumours. The success of these antibody–drug conjugates has spurred further interest in evaluating different antibodies and cytotoxic molecules, with more than 60 of these therapeutics currently under investigation
The Lancet Oncology , commentaire, 2018