Daraxonrasib

Erasca released a slew of Phase I data on Monday for its pan-RAS molecular glue candidate, drawing direct comparisons between the early results for ERAS-0015 and that of Revolution Medicine's pan-RAS inhibitor, daraxonrasib (RMC-6236).While investors and physicians alike have lauded Revolution's asset and its potential to change the treatment landscape for pancreatic cancer, Erasca's reveal wasn't welcomed nearly as warmly. The biotech's stock fell nearly 11% in the lead up to the announcement, and shed a further 35% during after-hours trade.   A potential lawsuit may be weighing Erasca's shares down. The company disclosed in a securities filing Monday that it has received a letter from Revolution alleging ERAS-0015 is "substantially equivalent" to compositions for pan-RAS molecular glue compounds claimed in its Patent No. 12,409,225. However, Erasca asserted that Revolution's claims "are without merit" and said it "intends to contest the allegations vigorously."Enthusiasm for Erasca's programme may also have been tempered by the disclosure of a patient death. A 66-year-old male with heavily pre-treated metastatic pancreatic cancer taking a 24-mg dose of ERAS-0015 experienced grade three pneumonitis, and he passed away after he elected to stop supportive care. For more on the high RAS bar set by Revolution, see KOL Views Q&A: Revolution's breakthrough with daraxonrasib will reverberate throughout pancreatic cancer landscape and Spotlight On: Daraxonrasib set to revolutionise pancreatic cancer treatment landscape.Overall response comparisonsErasca shared data from both the US Phase I AURORAS-1 trial, as well as the Chinese Phase I JYP0015M101 study being sponsored by Joyo Pharmatech, from whom the California-based biotech licensed ERAS-0015. Both dose-escalation trials evaluated the molecular glue in patients with RAS-mutant solid tumours. In 14 evaluable patients who received ERAS-0015 within the pharmacologically active dose (PAD) range of 16-32 mg every day, each showed at least a 75% reduction in KRAS G12X variant allele fraction in their circulating tumor DNA. Erasca also evaluated the overall response rate (ORR), including confirmed and unconfirmed responses, in patients with non–small-cell lung cancer (NSCLC) who received their first dose of ERAS-0015 at least 8 weeks prior to the data cutoff date in the US trial, or who had at least one post-dose tumour assessment in the Chinese trial, a measure dubbed uORR8wk. Among 37 NSCLC patients with second-line or later NSCLC who received a PAD of ERAS-0015, uORR8wk was 62%. According to Erasca, the result exceeded comparable data from a Phase I NSCLC study of daraxonrasib, published last year in the Journal of Thoracic Oncology, by 24 percentage points.In 16 NSCLC patients who had previously received an immune checkpoint inhibitor or platinum-based chemotherapy, uORR8wk reached 75%, besting daraxonrasib by 37 percentage points. For patients with pancreatic ductal adenocarcinoma (PDAC), Erasca measured the confirmed and unconfirmed ORR for patients in both the US and Chinese trials who received their first dose of ERAS-0015 at least 14 weeks prior to data cutoff date (uORR14wk). The results were compared against Phase I data for daraxonrasib in patients with PDAC presented at the 2024 EORTC-NCI-AACR symposium.Across all second-line patients with PDAC who received a PAD dose of ERAS-0015, the uORR14wk was 40%, exceeding daraxonrasib's results by 11 percentage points. For two patients taking the recommended expansion dose of 32 mg, uORR14wk reached 50%, ahead of daraxonrasib by 15 percentage points. Combination possibilitiesIn regards to safety, Erasca reported that ERAS-0015 was generally well tolerated with no dose-limiting toxicities, no discontinuations due to treatment-related adverse events (TRAEs), and a low rate of treatment interruptions or dosing reductions due to TRAEs. However, on a call to discuss the data, several investors sought more information on the patient death due to pneumonitis, seeming especially concerned with whether ERAS-0015's tolerability profile would limit its potential to be combined with other treatments. CEO Jonathan Lim emphasised that the withdrawal of supportive care is the main reason why the patient progressed from a grade three case of pneumonitis. He also noted that ERAS-0015's combinability with the anti-EGFR mAb Vectibix (panitumumab) "is very promising." "We also think that the overall lower frequency and severity of rash, GI [gastrointestinal] and stomatitis TRAES bodes well for combining this with other standard of care agents like chemotherapy and checkpoint inhibitors, for instance," Lim added. With monotherapy expansion and combination dose escalation cohorts now active in the US AURORAS-1 trial, Erasca is expecting data to read out in the first half of 2027.