On April 18, 2023 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported that promising initial Phase 1b dose escalation data from FLAGSHP-1 for ERAS-601 in combination with cetuximab (ERBITUX) in patients with advanced solid tumors as part of a poster presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in Orlando, Florida. ERAS-601 is a potent, selective, oral small molecule SHP2 inhibitor with best-in-class potential (Press release, Erasca, APR 18, 2023, View Source [SID1234639359]). The poster is available online at Erasca.com/science/presentations.

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"We are pleased with the outcome of the FLAGSHP-1 dose escalation evaluation of ERAS-601 plus cetuximab, which supports ERAS-601 being a backbone for combination therapy. The combination with cetuximab was well-tolerated with favorable pharmacokinetics and no apparent drug-drug interactions. In addition, to our knowledge, this is the first clinical evaluation of a SHP2 inhibitor and EGFR monoclonal antibody, the combination of which effectively inhibits oncogenic receptor tyrosine kinase signaling," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "That we saw predominantly low-grade adverse events (AEs) reinforces our hypothesis that a ‘three weeks on, one week off’ dosing regimen for ERAS-601 in combination may lead to fewer and milder AEs."

Dr. Lim continued, "The stable disease observed during this initial all comers dose escalation evaluation in heavily pretreated patients supports our plan to explore preliminary efficacy in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), an indication of high unmet need, with the now identified maximum tolerated dose (MTD) for the combination. We believe this patient population may be particularly responsive to this combination based on encouraging synergistic activity observed in preclinical studies. We expect to share initial Phase 1b dose expansion combination data in the first half of 2024."

Poster Presentation Highlights
Preliminary dose escalation results of ERAS-601 in combination with cetuximab in FLAGSHP-1: A Phase I study of ERAS-601, a potent and selective SHP2 inhibitor, in patients with previously treated advanced or metastatic solid tumors
ERAS-601 in combination with cetuximab inhibits RAS/MAPK signaling at multiple nodes which is predicted to limit the development of treatment resistance and offer more robust synergistic anti-tumor activity over monotherapy alone. Characterization of the safety profile, determination of the maximum tolerated dose (MTD)/recommended dose (RD), and characterization of the pharmacokinetic profile of ERAS-601 in combination with cetuximab was evaluated as part of the Phase 1/1b FLAGSHP-1 trial in patients with advanced or metastatic solid tumors.

ERAS-601 in combination with cetuximab shows promising preliminary safety and tolerability with reversible and manageable treatment-related adverse events (TRAEs)
Only grade 1 or 2 TRAEs occurred at or below the combination MTD for ERAS-601
ERAS-601 MTD was determined to be 40 mg BID 3/1 (three-week dosing followed by a one-week break) in combination with cetuximab (500 mg/m2) administered every 2 weeks
Initial Phase 1b dose expansion data in HPV-negative HNSCC tumors (NCT04670679) is expected in H1 2024