In KRASG12X colorectal cancer models (Fig. 3C), ORR (26%, 6/23) and DCR (52%, 12/23) were lower than those observed in NSCLC and PDAC models; this may reflect the presence of multiple oncogenic drivers and/or EGFR-mediated adaptive feedback to RAS/MAPK pathway signaling inhibition that is particularly resilient in colorectal cancer, as has been observed following BRAF and/or inactive-state selective KRASG12C inhibition (13, 14). Here, BRAF is linked to colorectal cancer.