The SHERPA trial: A phase I study combining SHP2 inhibitor RMC-4630 and ERK inhibitor LY3214996 in patients with KRAS-mutant pancreatic, non-small cell lung and colorectal cancer.

doi:10.1016/j.ejca.2026.116782

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The SHERPA trial: A phase I study combining SHP2 inhibitor RMC-4630 and ERK inhibitor LY3214996 in patients with KRAS-mutant pancreatic, non-small cell lung and colorectal cancer.

European journal of cancer (Oxford, England : 1990) - 18 Jun 2026

Kanhailal Ashwini C, Knikman Jonathan E, Zielhuis Sybrand W J, Kodach Liudmila L, Bernards René, Huitema Alwin D R, Tibben Matthijs, Voest Emile E, Gerrits Brent M, Huisman-Siebinga Hinke, Steeghs Neeltje, Mainardi Sara, Opdam Frans L

Abstract excerpt

INTRODUCTION: PDAC has high mortality rates and limited treatment options. KRAS mutations are present in > 90% of patients with PDAC, causing constitutive activation of the MAPK pathway. Preclinical studies demonstrated synergistic antitumor activity in in vivo and in vitro KRAS-mutant PDAC models by combining SHP2 and ERK inhibition. Therefore, the safety of combining SHP2 inhibitor RMC-4630 and ERK inhibitor...

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PMID: 42114409
DOI: 10.1016/j.ejca.2026.116782

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KRAS

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