Skip to main content
Premium Trial:

Request an Annual Quote

Erasca Begins Phase Ib/II Master Protocol Trial of ERAS-007 in Gastrointestinal Cancers

NEW YORK – San Diego-based Erasca has begun HERKULES-3, a Phase Ib/II master protocol study of its ERK1/2 inhibitor ERAS-007 in combination with other therapies in gastrointestinal cancer patients with various tumor mutations.

Initially, the study will enroll advanced colorectal cancer patients with BRAF V600E, KRAS, or NRAS mutations, which together drive more than half of these tumor types. BRAF V600E mutations occur in 10 percent of colorectal cancers, while KRAS and NRAS mutations show up in up to 50 percent of tumors. Although there are targeted treatment options for BRAF-mutated colorectal cancer, patients rapidly progress after a period of benefit. Meanwhile, there are no approved treatments currently for colorectal cancer patients with KRAS or NRAS mutations.

"A major barrier to durable responses with current treatment regimens for gastrointestinal cancers is the emergence of resistance mechanisms, which are often associated with reactivation of the MAPK pathway," Erasca cofounder and CEO Jonathan Lim said in a statement. "We have developed HERKULES-3 … to evaluate ERAS-007 in rational combinations to assess the possibility of reducing susceptibility to resistance and increasing durability of treatment."

Based on preclinical data, the company will explore ERAS-007 in combination with already available treatments for BRAF V600E-mutant metastatic colorectal cancer, the BRAF inhibitor encorafenib (Pfizer's Braftovi) and the EGFR inhibitor cetuximab (Merck KGaA/Eli Lilly's Erbitux). The company announced it had partnered with Pfizer to study the triplet regimen earlier this month.

Erasca will also pair ERAS-007 with the CDK4/6 inhibitor palbociclib (Pfizer's Ibrance) in metastatic colorectal cancer patients with KRAS or NRAS mutations.

In HERKULES-3, a dose escalation and expansion trial, researchers will study the safety, tolerability, and preliminary efficacy of the ERAS-007-containing regimens in these two cohorts. In future sub-studies of HERKULES-3, Erasca will explore the activity of ERAS-007 combination regimens in other gastrointestinal cancers.

Earlier this month, Erasca announced the start of HERKULES-2, another Phase Ib/II study of ERAS-007 with the EGFR inhibitor osimertinib (AstraZeneca's Tagrisso) in advanced EGFR-mutated NSCLC.