On November 30, 2022 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 a clinical trial collaboration and supply agreement (CTCSA) with Pierre Fabre for the BRAF inhibitor encorafenib (BRAFTOVI) within key international territories (Press release, Erasca, NOV 30, 2022, View Source [SID1234639374]).

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This agreement will support a clinical proof-of-concept trial evaluating ERAS-007, an oral ERK1/2 inhibitor, in combination with encorafenib and the anti-EGFR antibody cetuximab for the treatment of patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC). This combination is being investigated as part of the ongoing Phase 1b/2 HERKULES-3 master protocol in patients with gastrointestinal (GI) malignancies. Erasca will sponsor the trial, and Pierre Fabre will supply encorafenib in the Pierre Fabre territories which include Europe and Asia Pacific (excluding Japan and South Korea).

"We are excited to work with Pierre Fabre, a leader in precision oncology, on an international collaboration to explore ERAS-007 in combination with encorafenib and cetuximab in BRAF mCRC," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "This partnership complements our existing CTCSA with Pfizer for encorafenib within the United States and other markets. Resistance mechanisms, particularly through MAPK reactivation, limit long-term benefit with current standard of care BRAF-targeted treatments. By blocking RAS/MAPK pathway signaling at the most distal node, ERK1/2, ERAS-007 can potentially prevent pathway reactivation."

Worldwide, approximately 1.8 million cases of CRC are diagnosed annually, with BRAF V600E mutations occurring in approximately 10% of these patients. Encorafenib in combination with cetuximab was approved by the FDA in April 2020 for previously treated patients with BRAF V600E-mutant mCRC. While the combination demonstrated improved overall survival over chemotherapy, only 20% of patients experienced an objective response, with a progression-free survival of approximately four months. Emergence of resistance remains a major therapeutic barrier to long-term clinical benefit. Erasca is exploring whether ERK inhibition with ERAS-007 in combination with encorafenib plus cetuximab can reduce the emergence of resistance and further improve treatment benefit for patients with BRAF V600E-mutant mCRC.

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. ERAS-007 is being investigated across the series of HERKULES clinical trials that span multiple tumor types and includes both monotherapy and combinations with approved and investigational agents, such as RTK, SHP2, RAS, RAF, and/or cell cycle inhibitors. HERKULES-1 is 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. HERKULES-2 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer (NSCLC). HERKULES-3 is a Phase 1b/2 master protocol clinical trial for ERAS-007 in combination with various agents in patients with GI cancers.