Combining Immune Checkpoint Inhibitors with Targeted Therapies Chris Boshoff Pfizer, Inc., New York, NY, USA
Considering the hundreds of immune checkpoint blocker (ICB) combination studies ongoing, there is a paucity of significant number of combinations demonstrating early signs of efficacy. Reasons for this include the lack of biomarker selection in most of these studies, the fact that the vast majority of studies are single arm experiences where it could be difficult to decipher the exact contribution of the various components, and the lack of preclinical data supporting that a rational combination is being tested in the clinic. Targeted therapies with high objective response rates may serve as 'autologous cancer vaccines', inducing killing of cancer cells, resulting in the release of neoantigens which can then be presented by APCs to T-cells. Killing tumor cells may also re-balance the metabolism of the TME, restoring T-cell nutrition. Certain targeted therapies could directly lead to the activation or recruitment of tumor-directed T-cells. It is also postulated that targeted agents that directly kill tumor cells, with release of tumor antigens, may focus the immune response generated by ICBs towards tumor antigens, rather than self-antigens expressed on normal tissues, resulting in fewer immune-related adverse events. When combined, these therapies may therefore have an additive or even synergistic effect that could potentially further improve overall survival by raising the tail of the survival curve. I will review our rationale for combining a VEGFR inhibitor (axitinib), a CDK4/6 inhibitor (palbociclib), and a PARP inhibitor (talazoparib), with ICBs.
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