Extended Data Fig. 3: Dose dependent plasma exposure, tolerability, pharmacodynamic modulation and efficacy of MRTX1133.
From: Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor
(a) MRTX1133 was administered as a single dose via intraperitoneal injection at the dose levels indicated (n = 3 mice/group). The amount of MRTX1133 detected in plasma was plotted as ng/mL concentrations over time. Data shown as mean+/− standard deviation (SD). (b) MRTX1133 was administered BID daily via intraperitoneal injection at the dose levels indicated for 28 days in mice HPAC xenograft-bearing mice (n = 5 mice per group). Data are shown as mean body weights+/− standard error of the mean (SEM). Body weights were evaluated every 3–5 days. (c) Modulation of ERK1/2 phosphorylation (Tyr202/Thr204) and MRTX1133 plasma concentration (n = 3 mice/group) with vehicle or MRTX1133 administered as a single dose to mice bearing GP2D xenografts. Data shown as mean + /− SD. (D) MRTX1133 was administered intraperitoneally to mice bearing established GP2D xenografts at 30 mg/kg twice daily (BID). Dosing was initiated when tumors were ~250 mm3 (n = 5/group). MRTX1133 was administered to mice daily until Day 27. Data are shown as mean tumor volume + /− (SEM). Tumor volumes at Day 27 were determined to be statistically significant vs vehicle control two-tailed Student’s t-test (p-value <0.05).
