Tumors are under constant surveillance by the immune system, and as cancers grow and evolve, they must find new ways to evade immune detection.  The field of Immuno-oncology, or harnessing the body’s immune system to fight cancer, is one of the most promising new areas in cancer research of the last decade.  The unprecedented success of the so-called checkpoint inhibitors, such as the PD-1 and CTLA4 monoclonal antibodies, has generated a great deal of interest in identifying therapies which can combine with checkpoint inhibitors and increase their success rate and duration.  For most approved indications, PD-1 antibodies have a response rate of about 20-30%, and thus there is a need to identify agents which can synergize with these therapies to prevent resistance.  ZEN-3694 targets several mechanisms of resistance to PD-1 antibodies, including the upregulation of alternate checkpoint receptors, and the recruitment of suppressive cells to the tumor microenvironment (see poster for details).
These data suggest that ZEN-3694 could synergize well with PD-1
antibodies by targeting several mechanisms of checkpoint resistance.