Abstract
RMC-4630 is a potent, selective, orally bioavailable allosteric inhibitor of SHP2, a protein tyrosine phosphatase functioning downstream of multiple RTKs as a convergent node in RAS signaling. In a Phase 1b monotherapy study, RMC-4630 demonstrated acceptable safety and tolerability with a novel intermittent dosing schedule (Day 1 and Day 2 of each week) and single agent activity in KRASG12C NSCLC tumors. Tumor and blood-based immune-oncology biomarkers demonstrated preliminary evidence of anti-tumor immune activation, supporting an immune-mediated mechanism of action for SHP2 in addition to modulation of RTK signal transduction.
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