Erasca (ERAS) Study result summary

Unmet need and study rationale

• Significant unmet need persists in RAS-mutant tumors, including NSCLC, PDAC, and CRC, despite recent advances in targeted therapies.

• ERAS-0015 is designed as a pan-RAS molecular glue with improved pharmacokinetics, potency, and tumor distribution.

• Preclinical data show ERAS-0015 has higher oral bioavailability, lower clearance, and greater potency compared to benchmark RMC-6236.

Study design and objectives

• Preliminary Phase I data for ERAS-0015 presented from two parallel first-in-human trials in the U.S. and China, focusing on RAS-mutated solid tumors, especially NSCLC, PDAC, and CRC.

• Dose escalation and expansion phases evaluated oral ERAS-0015 from 2 to 40 mg daily, with recommended doses for expansion set at 24 and 32 mg.

• Primary and secondary endpoints included safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy.

• Patient populations were generally similar between trials, with most patients heavily pretreated and the U.S. cohort slightly more heavily pretreated.

• The study aimed to demonstrate differentiation in efficacy, safety, and combinability versus a comparator molecule.

Pharmacokinetics and pharmacodynamics

• ERAS-0015 showed rapid absorption, dose-dependent PK exposure up to 40 mg with no plateau, and low to moderate variability.

• Pharmacologically active doses identified as 16-32 mg daily, exceeding target efficacy thresholds.

• PK profiles were comparable between U.S. and China trials, supporting generalizability.

• At PAD, 100% of patients showed at least 75% reduction in KRAS G12X ctDNA, with robust target engagement and 5 achieving complete clearance.