ERAS-007 + palbociclib

ERAS-007 + palbociclib is an investigational **oral combination therapy** for cancer, currently being evaluated primarily for KRAS- and NRAS-mutant metastatic colorectal cancer (CRC) and KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). ERAS-007 is a selective, orally bioavailable small molecule inhibitor targeting ERK1/2—the terminal kinases of the RAS/MAPK signaling pathway, which is frequently dysregulated in various cancers. Palbociclib is a small molecule inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), approved and marketed as Ibrance for breast cancer, and blocks cell cycle progression. The rationale for combination is preclinical data suggesting that dual inhibition of the ERK pathway and the cell cycle may overcome adaptive resistance in RAS-driven tumors and result in synergistic anti-tumor effects. The combination is being evaluated in the Phase 1b/2 HERKULES-3 study (NCT05039177), sponsored by Erasca with palbociclib supplied by Pfizer, in patients with advanced GI cancers, specifically targeting genetically defined subgroups[1][3][5][7].