Phase 1 Trial to Test if Two Drugs Can Work Together to Treat Patients with RAS/MAPK Pathway-Driven Cancers

The first patient was enrolled in a phase 1b trial evaluating the combination of the ERK1/2 inhibitor ERAS-007 and SHP2 inhibitor ERAS-601 in patients with RAS/MAPK pathway-driven cancers, according to a press release from Erasca, the manufacturer of these drugs.

Of note, the ERK1/2 is a central signaling pathway that regulates cell proliferation, differentiation and death while SHP2 regulates immune cell function. MAPK pathways relay and amplify signals from stimulus which leads to cell differentiation, growth and death. Abnormal MAPK signaling can lead to uncontrolled cell growth and resistance to cell death, which can lead to cancer.

Similarly, mutations in the RAS genes can lead to uncontrolled cells growth and allow cells to evade death signals. RAS mutations also make cells resistant to certain therapies used to treat cancer.

This goal of phase 1 of this trial, named HERKULES-1, is to study the safety, tolerability and preliminary efficacy of this drug combination for patients with RAS/MAPK pathway driven-tumors as well as to determine the best dosage of ERAS-007 and ERAS-601.

Once this correct dosage is determined, the trial will move onto phase 2, where the combination of ERAS-007 and ERAS-601 will be tested on patients with other types of mutations, such as patients with class 2 and 3 BRAF mutations. Of note, BRAF is a gene that encodes protein (also called BRAF) which promotes cell division. Mutations are classified as class 2 when it has intermediate kinase activity and class 3 when it has low kinase activity.

Dr. Jonathan E. Lim, CEO of Erasca, noted that this approach is supported by early clinical data which illustrated that four out of nine patients with BRAF-driven cancers responded favorably to treatment with either ERAS-007 or ERAS-601. Three of these four patients had class 2 or 3 BRAF mutations.

“ … We look forward to exploring the potential to address the high unmet need in these BRAF subtypes, which have no approved targeted therapies and represent up to 25% of all BRAF-driven tumors,” Lim said in the release.

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