The investigational pan-RAS inhibitor generated robust responses across 2 phase 1 dose-escalation studies that numerically exceeded historical benchmarks.
The investigational pan-RAS inhibitor ERAS-0015 demonstrated robust responses and was well tolerated in patients with RAS-mutant solid tumors, including non–small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC), based on early data from ongoing phase 1 dose-escalation studies.1
Pooled data originating from the ongoing phase 1 AURORAS-1 trial (NCT06983743) in the United States and phase 1/2 JYP0015M101 (NCT06895031) trial in China showed response rates with the agent that numerically exceeded historical benchmarks reported for standard therapies in these settings. At data cutoffs of April 4, 2026 (AURORAS-1), and February 27, 2026 (JYP0015M101), ERAS-0015 produced unconfirmed overall response rates (uORRs) of 62% (n = 37) in second-line or later KRAS G12X–mutant NSCLC and 40% (n = 20) in second-line KRAS G12X–mutant PDAC at pharmacologically active doses (PADs) of 16 to 32 mg once daily.
In NSCLC, ERAS-0015 at PADs of 16 to 32 mg produced a uORR of 75% (n = 16) in patients with KRAS G12X–mutant disease who had previously received checkpoint inhibitors and platinum-based chemotherapy. At the selected recommended doses for expansion (RDEs) of 24 to 32 mg once daily, the uORR was 64% (n = 25) in second-line or later NSCLC. In PDAC, the agent achieved a uORR of 42% (n = 12) at RDEs of 24 to 32 mg in second-line disease. Higher response rates were observed at specific dose levels, including 50% (n = 2) at 32 mg once daily.
Responses appeared durable at the time of analysis, with most responding patients remaining on treatment. In NSCLC, 23 of 24 responders continued therapy; in PDAC, 20 of 23 responders remained on treatment at the data cutoff.
Regarding safety, the agent led to mostly low-grade adverse effects (AEs), and no dose-limiting toxicities (DLTs) were observed across dose levels evaluated through the March 31, 2026, data cutoff.
“We are thrilled with the robust efficacy results demonstrated so far by our pan-RAS inhibitor ERAS-0015 in patients with lung and pancreatic cancer,” Jonathan E. Lim, MD, chairman, chief executive officer, and cofounder of Erasca, stated in a news release. “The magnitude of clinical benefit seen during dose escalation is particularly striking and compares favorably with other pan-RAS, pan-KRAS, or KRAS-mutant selective inhibitors. This efficacy is accompanied by generally well-tolerated safety results, primarily characterized by manageable, low-grade AEs. Notably, preliminary data support [that] ERAS-0015 may be combined with standard-of-care doses of panitumumab, positioning it as a potential backbone therapy for future combination regimens. Together, we believe these findings support the best-in-class potential of ERAS-0015, and we look forward to continued progress in our phase 1 monotherapy dose expansion cohorts and combination dose escalation cohorts.”
ERAS-0015 is an investigational, oral pan-RAS molecular glue designed to potently inhibit RAS signaling and address a broad range of RAS-driven tumors. The agent is intended to overcome resistance associated with mutation-selective inhibitors by targeting both mutant and wild-type RAS isoforms. Findings from preclinical studies have demonstrated favorable absorption, distribution, metabolism, and excretion characteristics, as well as consistent pharmacokinetic (PK) properties across multiple animal models.
AURORAS-1 is a first-in-human, phase 1/1b, open-label, multicenter clinical study evaluating ERAS-0015 as both monotherapy and in combination with other cancer therapies in patients with advanced RAS-mutant solid tumors.2 In applicable cohorts, patients must have pathological documentation of tumor type and mutation prior to the first dose of study drugs.
One of the following 3 conditions must also apply to patients:
Eligible patients receive ERAS-0015 orally once daily across escalating dose levels, with the goal of identifying a pharmacologically active dose range and RDEs. For those receiving ERAS-0015 in the combination cohort, the agent is administered alongside either intravenous pembrolizumab (Keytruda) or panitumumab (Vectibix).
The study’s primary end points include PK, pharmacodynamic (PD), and safety measures; preliminary efficacy outcomes are assessed as secondary end points.
This multicenter, open-label study is evaluating the safety, tolerability, PK, and clinical activity of JYP0015 in patients aged 18 to 75 years with histologically or pathologically confirmed solid tumors that harbor RAS mutations as determined by molecular testing. Patients also must have disease progression or intolerance after adequate standard treatment and have an ECOG performance status of 0 or 1.3
The study comprises a phase 1 dose-escalation portion and phase 2 indication expansion. In phase 2, the therapeutic potential of JYP0015 monotherapy is explored at the RP2D across 4 predefined cohorts: PDAC, NSCLC, colorectal cancer (CRC), and other advanced solid tumors. All patients will receive JYP0015 as an oral tablet.
The study’s primary end points are the incidence of DLTs, AEs, and ORRs.
PD analyses demonstrated consistent target engagement, with 100% of evaluable patients (n = 14) achieving at least a 75% reduction in KRAS G12X circulating tumor DNA variant allele fraction, including complete clearance in 5 patients.1
Rates of dose interruptions and reductions due to treatment-related AEs (TRAEs) were low, and no discontinuations due to TRAEs were reported. The safety profile supported continued dose escalation and the selection of 24 mg and 32 mg once daily as RDEs for further study.
Of note, preliminary combination data also suggested that ERAS-0015 may be safely combined with panitumumab, with no DLTs observed and early evidence of antitumor activity in a patient with metastatic CRC.
Expansion cohorts and combination dose-escalation studies for ERAS-0015 are ongoing, with additional data from the AURORAS-1 trial expected to read out in 2027. Future development plans include evaluating ERAS-0015 as part of combination regimens and continuing investigation in tumor-specific cohorts.
Parallel efforts include the development of other RAS-targeted agents, such as ERAS-4001, which is being evaluated in the phase 1 BOREALIS-1 trial (NCT07021898) in patients with KRAS-mutant solid tumors. Preliminary data from the monotherapy cohort are anticipated in 2026, and the initiation of monotherapy expansion cohorts and combination dose escalation cohorts is planned for 2027.
