Erasca’s ERAS-0015 Shows 62–75% Response in KRAS G12X NSCLC Phase 1 Trial
Erasca reported Phase 1 dose escalation data showing monotherapy overall response rates of 62% in second-line KRAS G12X NSCLC at 16-32 mg QD and up to 75% in post-ICI/platinum NSCLC. ERAS-0015 also achieved 40-50% uORR in second-line KRAS G12X pancreatic cancer with no DLTs and low-grade adverse events.
1. Preliminary Efficacy Results
In KRAS G12X non-small cell lung cancer, ERAS-0015 achieved a 62% unconfirmed overall response rate (uORR) in second-line or greater patients at 16-32 mg QD and 75% uORR in post-ICI/platinum settings, with 64% uORR at recommended expansion doses of 24-32 mg QD. In second-line KRAS G12X pancreatic cancer, uORR ranged from 40% at 16-32 mg QD to 50% at 32 mg QD in small cohorts.
2. Safety and Tolerability
Treatment was generally well tolerated with primarily low-grade adverse events, no dose-limiting toxicities as of data cutoff, a low rate of dose interruptions or reductions, and no treatment discontinuations due to adverse reactions.
3. Pharmacokinetics and Pharmacodynamics
ERAS-0015 displayed dose-dependent pharmacokinetics up to the maximum administered dose of 40 mg QD with no exposure plateau. All 14 evaluable patients at pharmacologically active doses showed at least a 75% reduction in KRAS G12X circulating tumor DNA, including 5 patients with complete ctDNA clearance.
4. Next Steps and Timeline
The company plans to report data from monotherapy dose expansion and combination dose escalation cohorts in first half 2027. A live webcast and conference call will discuss these preliminary findings and outline future trial designs.