On June 2, 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 trial to investigate the ERK1/2 inhibitor ERAS-007 in combination with a KRAS G12C inhibitor in KRAS G12C-driven non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) (Press release, Erasca, JUN 2, 2022, View Source [SID1234639378]).

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!

"We look forward to ERAS-007 being evaluated in this trial, based in part on ERAS-007’s ability in preclinical studies to robustly shut down oncogenic signaling," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "This trial not only helps to broaden the therapeutic development of ERAS-007, but also complements the patient subgroups within our ongoing HERKULES-2 and HERKULES-3 master protocols. Additionally, it may provide proof-of-concept data supporting the addition of ERAS-007 as a treatment option to overcome RAS/MAPK resistance with KRAS G12C inhibitors. We look forward to potentially partnering with the team to explore the therapeutic potential of this combination."

Ryan Corcoran, M.D., Ph.D., Director of the Gastrointestinal Cancer Center Program at Massachusetts General Hospital and Associate Professor of Medicine at Harvard Medical School, added, "While adaptive feedback mechanisms can overwhelm MEK inhibitors, ERK inhibitors potentially can overcome drug resistance mechanisms that involve reactivation of RAS/MAPK pathway signaling. We look forward to evaluating whether the ERK1/2 inhibitor ERAS-007 has the potential to overcome feedback mechanisms and help address the limited efficacy of single agent KRAS G12C inhibitors."

A Phase 1b clinical proof-of-concept trial will evaluate ERAS-007 in combination with a KRAS G12C inhibitor in patients with NSCLC and CRC harboring a KRAS G12C mutation. Additional preclinical and clinical laboratory research will be conducted to further understand the activity and safety of this combination in these patient populations. The trial will be led by principal investigators Scott Kopetz, M.D., Ph.D., Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, Dr. Corcoran, and Pasi Janne, M.D., Ph.D., Professor of Medicine at Harvard Medical School. Drs. Corcoran and Kopetz recently received a grant from Stand Up To Cancer (SU2C).

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 is a Phase 1b/2 clinical trial for ERAS-007 as a single agent and in combination with the SHP2 inhibitor ERAS-601 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.