On September 8, 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 a clinical trial collaboration and supply agreement with Pfizer Inc. (NYSE: PFE) for the BRAF inhibitor encorafenib (BRAFTOVI) (Press release, Erasca, SEP 8, 2021, View Source [SID1234639384]).
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This agreement will support a clinical proof-of-concept study evaluating ERAS-007, an oral ERK1/2 inhibitor, in combination with encorafenib and the EGFR inhibitor cetuximab for the treatment of patients with BRAF V600E-mutant mCRC. This combination will be investigated as part of the Phase 1b/2 HERKULES-3 trial expected to initiate in the second half of 2021. Erasca will sponsor the study, and Pfizer will supply encorafenib. The two companies will form a Joint Development Committee to review the clinical trial results.
"We are excited to work with Pfizer to explore this promising combination in colorectal cancer," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "MAPK signaling is constitutively activated in patients with BRAF V600E mutations, who often have a poor prognosis. Combining upstream EGFR inhibition, midstream BRAF inhibition, and downstream ERK inhibition fits squarely within Erasca’s strategies to erase cancer and has potential to limit pathway reactivation, offering the therapeutic potential to comprehensively shut down the RAS/MAPK pathway in this tumor type."
Worldwide, approximately 1.8 million cases of CRC are diagnosed annually, with BRAF V600E mutations occurring in approximately 10% of these patients. The combination of encorafenib and cetuximab was approved in April 2020 for previously treated patients with BRAF V600E-mutant mCRC. The combination demonstrated improved overall survival compared to the chemotherapy control arm; however, only 20% of patients experienced an objective response, and the progression-free survival was approximately four months. Therefore, emergence of resistance is 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 a series of four 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 clinical trial for ERAS-007 in combination with various agents in patients with non-small cell lung cancer. HERKULES-3 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with gastrointestinal cancers. HERKULES-4 is a Phase 1b/2 clinical trial for ERAS-007 in combination with various agents in patients with hematologic malignancies.