Japan-based Daiichi Sankyo has entered a preclinical research collaboration with US-based Puma Biotechnology and Memorial Sloan Kettering Cancer Centre (MSK) to assess a combination therapy for the treatment of HER2-mutated/HER2-positive solid tumours.
The firms will explore Daiichi Sankyo’s DS-8201, an investigational antibody-drug conjugate (ADC), in conjunction with Puma Biotechnology’s pan-HER tyrosine kinase inhibitor called neratinib (Nerlynx).
DS-8201 is being developed as a smart chemotherapy and contains a humanised HER2 antibody connected with a tetrapeptide-based linker to a new topoisomerase I inhibitor payload.
Neratinib was approved by the US Food and Drug Administration (FDA) for the extended adjuvant treatment of adults suffering from early stage HER2-positive breast cancer after adjuvant trastuzumab-based therapy.
The drug candidate is designed to deliver chemotherapy within cancer cells and decrease systemic exposure to the cytotoxic payload or chemotherapy.
A team of scientists and clinical investigators are set to utilise isogenic and patient-derived xenograft models to evaluate the susceptibility of HER2-mutated/positive cancers to DS-8201, neratinib and other therapies that target HER2.
Co-sponsored by Daiichi Sankyo and Puma Biotechnology, the research aims to interpret mechanisms of action and resistance of such tumours, and will investigate the potential for synergistic combinations.
Daiichi Sankyo Antibody Drug Conjugate Task Force global head and vice-president Tom Held said: “Since early clinical data suggests that DS-8201 may have activity beyond breast and gastric cancers, the archetype HER2-driven tumours, we are interested in studying this asset on a molecular level, as well as in combination with other HER2-targeting agents.
“In this collaboration, we are examining whether combining DS-8201 and neratinib, with its specific covalent binding to the HER2 receptor and associated increased internalisation, is a rational combination therapy strategy to pursue.”