RE:RE:RE:RE:RE:AstraZeneca's ADC disappoints - on severe adverse eventsA better mechanistic understanding of how the TME responds to ADC treatment could lead to durable responses because of amplification of the immune system. The next era of ADCs will be focused on strategies to overcome resistance and enhance efficacy by pairing ADCs with signaling pathway inhibitors, ICIs, other TME modifiers, such as ONCY's pelareorep, and emerging payloads.
And while delivery of either monotherapies or combination ADC therapies still lacks an effective means of patient selection, ONCY's biomarker studies have validateds biomarkers that can facilitate what ADC therapy is currently missing. This challenge is particularly critical in the present era where certain ADCs, such as Daiikai Sanky/AstraZeneca's Enhertu, Roche's T-DXd and Pfizer/Seagen, surpass limitations of our traditional breast cancer subtypes. Thus, the development of biomarkers, to determine the patient population likely to benefit from ADC treatment becomes imperative. To uncover such biomarkers, it is important to conduct studies using advanced analytic techniques of the entire microenvironment, such as single-cell and spatial “omics” and functional assays with tumor organoids and immune cells, which is what ONCY has been doing in its tranlational studies, such as in the Solti/Aware-1 study.
The understanding of how signaling networks change across cell types and how ONCY's pelareorep augments the function of effector immune cells and decrease regulatory immune cells (i.e.Tregs) has led to the development of new biomarkers in multiple cancers and to the ability for pelareorep to be combined with immune checkpoint inhibitors and potentially antibody drug conjugate (ADC) combinations.