MRTX849 represented an exciting advancement in KRASG12C inhibitors. Constrastingly, immune checkpoint monotherapy remains limited for most patients of non-small cell lung cancers (NSCLC). Since KRASG12C mutations are smoking-induced transversion mutations in a high mutation burden setting, Briere and colleagues tested MRTX849's potential to augment immune checkpoint therapy. Treatment with MRTX849 and anti-PD1 generated durable complete responses in the CT26 KrasG12C model that rejected re-challenge. MRTX849 increased M1-polarized macrophages and reduced intratumoral myeloid-derived suppressor cells in human tumor xenograft, syngeneic, and genetically engineered mouse (GEM) models. Their research demonstrates MRTX849 may enable the durable response of checkpoint inhibitors for a greater number of KRASG12C-mutant NSCLC patients.

Malignant pleural mesothelioma remains a deadly disease with unmet therapeutic needs. Due to the high occurrence of NF2 mutations, the Hippo pathway may be one avenue to meet this need. As YAP and TAZ have no known catalytic activity to inhibit,...

You do not currently have access to this content.