ESMO 2023 – the colorectal KRAS pipeline swells again

ESMO today saw late-breaking data on Amgen’s KRAS G12C inhibitor Lumakras plus Vectibix in late-line colorectal cancer. But yesterday another G12C contender, garsorasib from China’s InventisBio, outdid Amgen's agent in this setting. An ORR of 45% with a garsorasib/Erbitux combo, from an uncontrolled but multinational phase 2 trial, looks similar to the result with Mirati’s Krazati plus Erbitux in Krystal-1. The combo to beat remains Roche’s divarasib plus Erbitux, but tolerability will be important, and garsorasib/Erbitux seems the least toxic pairing so far. Although the latest Lumakras data, which were simultaneously published in NEJM, look underwhelming, Dr Clara Montagut of Hospital del Mar in Barcelona stressed to an ESMO press conference that Codebreak-300 was the first randomised, controlled trial of a G12C inhibitor in this setting; it tested the combo against physician’s choice of Lonsurf or Stivarga. However, the ESMO discussant, Dr Miriam Koopman of Utrecht University, questioned the use of PFS as primary endpoint and stressed the importance of OS, data on which remain immature. Mirati has said it intends to file Krazati in third-line disease this year, while a spokesperson for Amgen told ApexOnco that the group was "actively discussing" the Codebreak-300 data with regulators. 

Cross-trial comparison of KRAS G12C inhibitor combos in late-line colorectal cancer

Source: ESMO 2023, AACR 2023 & ESMO 2022.