Erasca reported preliminary Phase I dose-escalation data for ERAS-0015, its oral pan-RAS molecular glue, in patients with RAS-mutant solid tumors, with pooled findings from the U.S. AURORAS-1 trial and the China-based JYP0015M101 trial showing unconfirmed overall response rates of 62% in second-line or later KRAS G12X non-small cell lung cancer and 40% in second-line KRAS G12X pancreatic cancer at pharmacologically active doses.
At pharmacologically active doses of 16–32 mg once daily, 62% of 37 evaluable patients with 2L+ KRAS G12X NSCLC achieved an unconfirmed objective response at eight weeks, rising to 75% among the 16 patients in the post-ICI/platinum second- or third-line subgroup. At the recommended doses for expansion of 24–32 mg once daily, the unconfirmed response rate in 2L+ NSCLC was 64% across 25 patients. In KRAS G12X pancreatic cancer, 40% of 20 second-line patients responded at pharmacologically active doses at 14 weeks, with 42% responding among 12 patients at the recommended expansion doses; a 32 mg once-daily cohort of two patients produced a 50% unconfirmed response rate. Pharmacodynamic data showed that 100% of 14 patients at pharmacologically active doses achieved at least a 75% reduction in KRAS G12X circulating tumor DNA variant allele fraction, with five of those 14 reaching complete ctDNA clearance. No dose-limiting toxicities were observed as of either data cutoff, adverse events were predominantly low-grade, and no patients discontinued due to treatment-related adverse events. In the combination cohort evaluating ERAS-0015 with standard-of-care panitumumab in colorectal cancer, no dose-limiting toxicities were observed in three safety-evaluable patients, and one efficacy-evaluable patient achieved an unconfirmed partial response.
The AURORAS-1 trial is an ongoing Phase I dose-escalation study enrolling patients with RAS-mutant solid tumors in the U.S., with a data cutoff of April 4, 2026; the JYP0015M101 trial, sponsored by Joyo Pharmatech Co., Ltd. in China, carried a data cutoff of February 27, 2026. Efficacy data presented are pooled across both trials. The response rates are unconfirmed, the dataset remains preliminary and dose-escalation stage, and patient numbers in several subgroups — particularly the 32 mg pancreatic cancer cohort with two patients — are too small to draw conclusions. Confirmed response rates, duration of response, and progression-free survival were not reported. The company selected 24 mg and 32 mg once daily as go-forward monotherapy recommended doses for expansion, with monotherapy expansion and combination dose-escalation data now expected in the first half of 2027.