Investigators Initiate Treatment With ERAS-007 in Patients With EGFR-Positive NSCLC

The first patient has been dosed in the phase 1b/2 trial (NCT04866134) of ERAS-007, an extracellular signal-regulated kinase (ERK) inhibitor, for the treatment of advanced non-small cell lung cancer (NSCLC), according to a press release by Erasca, Inc.¹

In addition to being an ERK inhibitor, ERAS-007 targeted the RAS/MAPK pathway, allowing it to be used across a variety of tumor types. It has also demonstrated anti-tumor activity in cancers harboring BRAF, KRAS, NRAS, and HRAS mutations as well as a range of KRAS subtypes.

“As the foundation of Erasca’s lung cancer platform, HERKULES-2 is a master protocol designed to inhibit multiple oncogenic drivers of the RAS/MAPK pathway to address high unmet needs in lung cancer. Initially focused on patients with mutant EGFR or KRAS NSCLC, HERKULES-2 will further progress to evaluate other combinations targeting additional subtypes of NSCLC,” said Jonathan E. Lim, MD, Erasca’s chairman, CEO, and co-founder, in a press release. “Erasca’s series of HERKULES trials also includes tissue-specific master protocols in gastrointestinal cancers and hematological malignancies as well as a tissue-agnostic trial, tailored to evaluate promising combinations to inhibit oncogenic signaling and prevent the emergence of resistance.”

The trial, HERKULES-2 (NCT04959981), aims to determine the safety of ERAS-007 in NSCLC harboring an EGFR mutation. The open-label study has an estimated enrollment of 200 participants and an estimated completion date of March 2024. Primary end points include dose limiting toxicities, maximum tolerated dose, recommended dose, and adverse events. Secondary end points include plasma concentration, time to achieve Cmax, area under the curve, half-life, objective response rate, and duration of response.² 

The study will be split into a dose escalation part and a dose expansion part. During both parts, patients will receive ERAS-007 in combination with 80mg orally once daily of osimertinib (Tagrisso). Dose escalation will continue until unacceptable toxicity, disease progression, or withdrawal of consent. 

In order to participate in the study, patients must be 18 years or older, have confirmed NSCLC with an EGFRmutation, measurable disease, have adequate bone marrow and organ function, and ECOG status of 0 or 1, and be able to swallow oral medication. Patients who are receiving concurrent treatment, who have received prior immunotherapy, have unresolved toxicity from prior systemic therapy, impaired cardiovascular function, or a history of or current evidence of retinal pigment epithelial detachment are not eligible to participate.

HERKULES-2 is not the only trial involving ERAS-007. HERKULES-1 (NCT04866134) is evaluating the agent in patients with advanced or metastatic solid tumors as a monotherapy. Two additional studies are also planned. HERKULES-3, a phase 1b/2 clinical trial, will evaluate ERAS-007 in combination with various agents for the treatment of gastrointestinal cancer is expected to start by the end of the year. HERKULES-4, also a phase 1b/2 trial, will evaluate ERAS-007 in combination with other agent in hematologic malignances. It is expected to begin in the first quarter of 2022.

HERKULES-2 is currently recruiting in New Jersey and Tennessee.

_REFERENCES: 

_{Erasca announces first patient dosed in HERKULES-2 phase 1b/2 lung cancer master protocol evaluating ERAS-007 in multiple combinations. News release. Erasca. September 9, 2021. Accessed September 9, 2021. https://bit.ly/3hg26u2.}

_{A study of ERAS-007 in patients with advanced non-small-cell lung cancer (HERKULES-2). ClinicalTrials.gov. Accessed September 9, 2021. https://bit.ly/3jXa2SX.}