On September 9, 2021 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 dosing of the first patient in the HERKULES-2 Phase 1b/2 trial evaluating ERAS-007 in combination with various agents in patients with advanced non-small cell lung cancer (NSCLC) (Press release, Erasca, SEP 9, 2021, View Source [SID1234639383]).

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"As the foundation of Erasca’s lung cancer platform, HERKULES-2 is a master protocol designed to inhibit multiple oncogenic drivers of the RAS/MAPK pathway to address high unmet needs in lung cancer. Initially focused on patients with mutant EGFR or KRAS NSCLC, HERKULES-2 will further progress to evaluate other combinations targeting additional subtypes of NSCLC," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "Erasca’s series of HERKULES trials also includes tissue-specific master protocols in gastrointestinal cancers and hematological malignancies as well as a tissue-agnostic trial, tailored to evaluate promising combinations to inhibit oncogenic signaling and prevent the emergence of resistance."

HERKULES-2 will initially examine the safety, tolerability, and preliminary efficacy of ERAS-007 in combination with osimertinib (TAGRISSO) in patients with advanced NSCLC harboring an epidermal growth factor receptor mutation (EGFRm). After a recommended dose is determined, the Phase 2 expansion portion will further evaluate the safety and efficacy of the combination in patients whose disease has developed resistance to osimertinib, a setting in which there are currently no approved targeted therapies. Future sub-studies of HERKULES-2 will explore ERAS-007 or the SHP2 inhibitor ERAS-601 in combination with other agents in patients with different mutational subtypes, including a KRAS G12C mutation.

ERAS-007, a potential best-in-class inhibitor of the extracellular signal-regulated kinases (ERK), targets the terminal node of the RAS/MAPK pathway. The broad applicability of ERAS-007 across a wide range of indications and tumor types was recently highlighted in a preclinical study published in Cell Reports Medicine, supporting durable ERK blockade and potent antiproliferative efficacy in both solid tumor and hematological malignancy cell lines. ERAS-007 demonstrated preferential anti-tumor activity for tumor types harboring mutant BRAF, KRAS, NRAS, or HRAS, as well as robust inhibitory activity across a range of mutant KRAS subtypes.

About ERAS-007
ERAS-007 is a potential best-in-class ERK1/2 inhibitor being investigated alone or in combination with different inhibitors targeting upstream nodes of the MAPK pathway as part of Erasca’s MAPKlamp strategy. The extracellular signal-regulated kinases (ERK), ERK1 and ERK2, belong to a family of serine-threonine kinases that regulate cellular signaling and comprise the terminal node of the RAS/MAPK pathway. The broad therapeutic potential of ERAS-007 is being investigated initially across four HERKULES clinical trials that span multiple tumor types and include both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1, a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 (together, Erasca’s first MAPKlamp) in advanced solid tumors, and HERKULES-2, a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with NSCLC, are currently enrolling patients. HERKULES-3, a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal cancers, is expected to begin by year-end. HERKULES-4, a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with hematologic malignancies, is anticipated to begin in the first quarter of 2022.