Phase I study of lapatinib plus trametinib in patients with KRAS-mutant colorectal, non-small cell lung, and pancreatic cancer.

Huijberts SCFA, van Geel RMJM, van Brummelen EMJ, Opdam FL, Marchetti S, Steeghs N, Pulleman S, Thijssen B, Rosing H, Monkhorst K, Huitema ADR, Beijnen JH, Bernards R, Schellens JHM

KRAS oncogene mutations cause sustained signaling through the MAPK pathway. Concurrent inhibition of MEK, EGFR, and HER2 resulted in complete inhibition of tumor growth in KRAS-mutant (KRASm) and PIK3CA wild-type tumors, in vitro and in vivo. In this phase I study, patients with advanced KRASm and PIK3CA wild-type colorectal cancer (CRC), non-small cell lung cancer (NSCLC), and pancreatic cancer, were treated with combined lapatinib and trametinib to assess the recommended phase 2 regimen (RP2R).