Figure 4 from Abrogation of Oncogenic RAS Signaling by a RAS(ON) Inhibitor Doublet Primes Immune-Refractory KRASG12C-Mutant NSCLC for Immune Checkpoint Blockade

Le résumé fourni par la source

PK/TE/PD modeling of complementary mechanisms predicts the superiority of the RAS(ON) inhibitor doublet over monotherapies in the context of KRASG12C overexpression. A, The model captures the blood PK of daraxonrasib at 25 mg/kg and plasma PK of elironrasib at 100 mg/kg upon single and repeated daily administration. The simulated PK is shown by the solid lines. The observed data are shown by dots. B, Model captures the TE and PD upon single and repeated daily administration of elironrasib at 100 mg/kg and daraxonrasib at 25 mg/kg as single agents or in combination, as measured by the levels of non–cross-linked KRASG12C protein and DUSP6 mRNA expression, respectively. Simulated TE and PD are shown by the dash and solid lines, respectively. The observed TE and PD data are shown by circles and diamonds, respectively. C, The steady-state simulation of RAS pathway suppression as measured by DUSP6 mRNA expression relative to the baseline following daily administration of elironrasib at 30 or 100 mg/kg and daraxonrasib at 25 mg/kg as single agents or in combination. D, The steady-state simulation of RAS pathway suppression with different levels of KRASG12C protein as measured by DUSP6 mRNA expression relative to the baseline without KRASG12C overexpression, following daily administration of elironrasib at 30 or 100 mg/kg and daraxonrasib at 25 mg/kg as single agents or in combination. qd, every day.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.