This summer across the US the heat is on – really on – both outside and thanks to lead EpicentRx therapy and transforming growth factor beta (TGFβ) inhibitor, AdAPT-001, inside tumors as well.
Inside tumors it is the presence or absence of infiltrating T cells that determines whether tumors are referred to as inflamed/ “hot” or non-inflamed/ “cold”, respectively. Across cancer, cold tumors are in the majority by far, as hot tumors are much rarer, which presents a real clinical dilemma whether to treat with the superheroes of immunotherapy, checkpoint inhibitors (CIs), because only hot tumors tend to respond to them.
Therefore, the major push in oncology is to identify safe, well-tolerated therapies that not only turn cold tumors hot but also nicely complement checkpoint inhibitors, so that patient response rates, but not toxicity, dramatically increase. To call this a tall order is an understatement since improved efficacy with combination therapy from two checkpoint inhibitors together or a checkpoint inhibitor plus traditional chemotherapy, for example, usually comes at a cost of significantly increased toxicity.
AdAPT-001 is an exception to this trend because, to date in clinical trials, against all odds, it has managed to do what no other TGFβ inhibitor has done – which is to consistently turn cold tumors hot and to make them much more sensitive to checkpoint inhibitors as a result all without increased toxicity.
Checkpoint inhibitors have unquestionably revolutionized the treatment of cancer with the promise of durable responses and even, in some cases, cures, but the major catch is that they are mainly only active in the presence of hot, T-cell infiltrated tumors. The other major catch with them is that they are responsible for immune-related adverse events that vary from mild to life-threatening.
As a result, to experience the much more consistent thrill of victory against all cancer types, and not just a select few like melanoma, non-small cell lung cancer (NSCLC) and head and neck cancer, it is necessary to subject tumors to the agony of “de-heat” with a well-tolerated, non-overlapping, tumor-targeted therapy such as AdAPT-001 that is active on its own and also synergizes nicely with checkpoint inhibitors.