On October 20, 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 Pfizer Inc. (NYSE: PFE) for the CDK4/6 inhibitor palbociclib (IBRANCE) (Press release, Erasca, OCT 20, 2022, View Source [SID1234622228]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
This agreement will support a clinical proof-of-concept study evaluating ERAS-007, an oral ERK1/2 inhibitor, in combination with palbociclib for the treatment of patients with KRAS- and NRAS-mutant colorectal cancer (CRC) and KRAS-mutant pancreatic ductal adenocarcinoma (PDAC). The combination is currently being investigated as part of the ongoing Phase 1b/2 HERKULES-3 master protocol clinical trial in patients with gastrointestinal (GI) malignancies. Erasca is sponsoring the study, and Pfizer is supplying palbociclib at no cost.
"We are excited to expand our existing relationship with Pfizer to explore ERAS-007 in combination with palbociclib in RAS-mutated GI malignancies as part of our HERKULES-3 program," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "Preclinical evidence supports synergistic anti-tumor effects when downstream RAS/MAPK pathway inhibition is combined with cell cycle inhibition in CRC and PDAC. ERAS-007 blocks RAS/MAPK pathway signaling at the terminal node with robust inhibitory activity across RAS mutations, while data support palbociclib inhibition of CDK4/6 leading to cell cycle arrest. Based on their respective mechanisms of action, ERAS-007 and palbociclib offer a promising combination to overcome adaptive resistance in patients with these highly prevalent oncogenic drivers."
Worldwide, approximately 1.8 million cases of CRC are diagnosed annually, with about 50% of patients harboring KRAS or NRAS mutations. PDAC accounts for an estimated 0.5 million new cases diagnosed annually, with over 90% harboring a KRAS mutation. Lack of effective treatment availability and emergence of compensatory mechanisms of resistance continue to challenge the ability to achieve and maintain responses in these GI malignancies. Erasca is exploring whether inhibiting ERK1/2, the terminal node of the RAS/MAPK signaling pathway, in combination with palbociclib can limit the development of treatment resistance and further improve therapeutic benefits.
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 RAS/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 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 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.