Erasca Shares Phase 1 ERAS-0015 Data: 62% NSCLC Response, ctDNA Clearance Signals

Key Points

• ERAS-0015 showed strong activity in KRAS-mutant NSCLC: across second-line-plus patients treated ≥8 mg the objective response rate was 62%, and at the pharmacologically active dose (16–32 mg) all 14 patients achieved ≥75% reductions in KRAS mutant ctDNA with five complete clearances.
• Activity in pancreatic cancer was more modest (about 36%–41% in second-line cohorts) but appeared to deepen with longer follow-up, while an early colorectal combination with panitumumab (16 mg ERAS-0015) produced a partial response and no DLTs in the initial patients.
• Erasca selected 16–32 mg as pharmacologically active doses with recommended expansion doses of 24 and 32 mg; safety was generally manageable (rash, diarrhea, stomatitis, nausea) but included one treatment-related pneumonitis death, and select expansion/combination data are expected in H1 2027.

Erasca NASDAQ: ERAS presented a preliminary Phase 1 data update for ERAS-0015 (also referred to as ERAS-15), which management described as a “pan-RAS molecular glue,” highlighting early signals of efficacy across non-small cell lung cancer (NSCLC), pancreatic cancer, and early combination activity in colorectal cancer, alongside what the company characterized as a favorable pharmacokinetic profile and encouraging tolerability.

Jonathan Lim, CEO and Chairman, said the company is sharing results from two independent, parallel first-in-human trials—one conducted in China by Joyo, and one conducted in the U.S. by Erasca—arguing that the dual-trial approach provides a larger overall dataset and allows the company to discuss the “generalizability” of the observations between geographies. Lim cautioned that the company made cross-trial comparisons to a “comparator” drug using non-head-to-head datasets, and that such comparisons should be interpreted carefully.

Two parallel Phase 1 studies and dose selection

ERAS-0015 is being evaluated as an oral, once-daily therapy in dose escalation ranges from 2 mg to 40 mg in both the China and U.S. studies. Lim said eligibility criteria were broadly similar, with the key difference that the China trial allowed “any RAS-mutated solid tumor,” while the U.S. trial focused on pancreatic cancer, KRAS G12X/G13X lung cancer, and select KRAS G12X/G13X gastrointestinal tumors.

Dawei Xuan, SVP of Clinical Pharmacology, said ERAS-0015 demonstrated “well-behaved” pharmacokinetics in the clinic, including rapid absorption, a dose-dependent exposure increase across the evaluated range, and low-to-moderate variability. Based on steady-state concentrations relative to an exposure threshold derived from a CDX model, the company identified 16–32 mg daily as “pharmacologically active doses” (PAD). Xuan added that 24 mg and 32 mg daily were selected as recommended doses for expansion (RDEs), citing the totality of safety, tolerability, preliminary efficacy, and PK/PD data during escalation and referencing FDA’s Project Optimus.

Management also noted that single-dose PK profiles appeared “largely comparable” between the China and U.S. trials in a cross-trial comparison.

Biomarker activity and ctDNA reductions

Xuan said ERAS-0015 exposure translated into pharmacodynamic activity as measured by reductions in KRAS mutant allele fraction in circulating tumor DNA (ctDNA). At PAD, the company reported a statistically significant greater reduction compared to lower doses, and said all 14 patients treated at PAD achieved at least a 75% reduction in KRAS mutant allele fraction, including five patients with “complete clearance.”

Preliminary efficacy in lung and pancreatic cancer

Lim framed NSCLC, pancreatic cancer, and colorectal cancer as the “big three” tumor types for KRAS mutations due to the prevalence of KRAS-mutated disease. He said the company expects differing sensitivities to pan-RAS inhibition across these tumor types, and described ERAS-0015’s early data as supporting that thesis.

NSCLC: Lim reported that among second-line-plus patients with KRAS G12X lung cancer treated at 8 mg or above (U.S. and China combined), the objective response rate (ORR) was 62% (39 patients). In the subset treated at the PAD range of 16–32 mg (37 patients), he again cited a 62% response rate, stating responses were consistent across regions.

Lim highlighted a subgroup intended to represent patients who would traditionally receive docetaxel—post-checkpoint and platinum therapy, second- or third-line, and docetaxel-naïve—where ERAS-0015 at PAD showed a 75% response rate (16 patients). He also said that globally, response rates were 64% at the RDEs (24 and 32 mg).

Chief Medical Officer Shannon Morris provided additional detail, including separate China and U.S. efficacy-evaluable datasets. In the China trial’s efficacy-evaluable population at 16 mg and 24 mg (no 32 mg patients were included in the dataset shown), Morris cited a 63% response rate and a 73% response rate in the post-checkpoint/platinum, second/third-line, docetaxel-naïve subgroup. In the U.S. efficacy-evaluable population, Morris said the response rate was 60% in the 16–32 mg dose range, and 71% in a similar subgroup population (noting that subgroup included patients treated at ≥8 mg).

Morris also described a case study of a 70-year-old man with metastatic KRAS G12V NSCLC treated at 8 mg daily who had a 37% decrease in target lesions at first imaging and later achieved a confirmed partial response. She said the patient was able to come off oxygen within one week of starting therapy and reported only a grade 1 treatment-related rash as of the data cutoff.

Pancreatic cancer: Lim said pancreatic cancer responses can be delayed based on comparator disclosures, and presented ERAS-0015 response rates that increased with longer follow-up and earlier line of therapy. Using a second-line-only, ≥14-week follow-up methodology, Lim said ERAS-0015 produced “40%–50%” response rates across the PAD, RDE, and 32 mg-only dose ranges in an efficacy-evaluable population, and compared those figures to comparator response rates discussed in public disclosures.

Morris reported that in the China trial efficacy-evaluable population, second-line-plus KRAS G12X pancreatic cancer patients treated at 16–32 mg had a 36% response rate, rising to 41% in a more homogeneous second-line-only subgroup. She said the combined U.S. and China data suggest pancreatic cancer is less sensitive to ERAS-0015 than lung cancer, but emphasized disease stabilization and the potential for responses to mature with longer follow-up.

Morris highlighted a U.S. case study of a 75-year-old man with metastatic KRAS G12D pancreatic cancer who started at 8 mg daily, initially met RECIST progression criteria, then continued beyond progression and escalated to 16 mg. She said subsequent scans showed disappearance of a new lesion and up to a 33% decrease in target lesions, though the official RECIST outcome remained progressive disease.

Colorectal combination with panitumumab and early safety observations

Lim said colorectal cancer has been challenging for RAS/MAPK pathway inhibitor monotherapy due to EGFR-mediated adaptive resistance, which is why Erasca initiated a combination dose-escalation cohort of ERAS-0015 plus panitumumab in the first quarter, “ahead of schedule.” The company reported three enrolled patients in a 16 mg ERAS-0015 plus standard-dose panitumumab cohort; two completed the dose-limiting toxicity (DLT) window with no DLTs observed as of a March 31 cutoff.

Lim said the first efficacy-evaluable patient showed a partial response on the initial scan, and described a 77-year-old man with stage 4 KRAS G12D colorectal cancer treated with ERAS-0015 16 mg plus panitumumab who had 34% tumor shrinkage at first restaging and remained on treatment. Lim said treatment-related adverse events included low-grade rash, paronychia, pruritus, and mucositis.

On safety, the company presented treatment-related adverse event (TRAE) data from the U.S. trial and said differences in reporting practices made direct TRAE comparisons with the China trial difficult. Morris said the most common TRAEs (≥10%) at 16–32 mg in the U.S. were rash, diarrhea, stomatitis, and nausea. She also disclosed a treatment-related pneumonitis case that began as grade 3 and later resulted in death after the patient elected to discontinue aggressive supportive care.

In Q&A, management said it had not seen other grade 4 or grade 5 TRAEs. Lim noted pneumonitis is a rare toxicity seen across oncology drugs and said approved KRAS G12C inhibitors carry warnings for pneumonitis; he also referenced comparator disclosures of pneumonitis at “1 out of 50” monotherapy patients. Morris said the investigator believed the outcome “might have been different” had the patient continued supportive care.

Management also said it did not pursue dose escalation beyond 40 mg despite no protocol-defined DLTs at that level, citing toxicities that investigators and the company believed did not support continuing higher dosing given observed activity at 16–32 mg. Lim referenced grade 3 rash in two patients at 40 mg as part of the risk-benefit rationale.

Next milestones and development priorities

Lim said Erasca completed dose escalation in less than one year and identified two monotherapy RDEs. The company said it initiated monotherapy expansions and combination dose escalation ahead of schedule and narrowed guidance to “H1 2027” for select monotherapy expansion and combination dose escalation data.

In Q&A, Lim said the company plans to advance across all three tumor types, with a significant focus on combination strategies in the first-line pancreatic setting, including evaluation with regimens such as FOLFIRINOX and gemcitabine/Abraxane. He said second-line pancreatic development is “not off the table,” and described lung cancer as open to both second-line-plus and first-line opportunities.

About Erasca NASDAQ: ERAS

Erasca, Inc is a clinical‐stage biopharmaceutical company dedicated to the discovery and development of precision medicines for patients with cancer. The company focuses on small molecule therapeutics that target critical signaling pathways involved in tumor growth and survival, with a primary emphasis on inhibitors of the MAPK pathway. Erasca's approach is designed to deliver oral, targeted therapies that address both oncogene‐driven and immuno‐oncology indications, aiming to improve outcomes for patients with unmet medical needs.

Erasca's pipeline comprises multiple development candidates, including small molecule inhibitors engineered to disrupt key nodes in cancer cell signaling.

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