Ulixertinib Is Active, Safe for Pts With MAPK Mutant Solid Tumors

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ERK1/2 kinase inhibitor, ulixertinib, was used to treat cancer patients with MAPK mutant solid tumors.
ERK1/2 kinase inhibitor, ulixertinib, was used to treat cancer patients with MAPK mutant solid tumors.

(HealthDay News) -- The ERK1/2 kinase inhibitor ulixertinib is active and safe for patients with advanced solid tumors, according to a study published in Cancer Discovery.

Ryan J. Sullivan, MD, from the Massachusetts General Hospital Cancer Center in Boston, and colleagues enrolled 135 patients to an accelerated 3 + 3 dose-escalation cohort and 6 distinct dose-expansion cohorts in a multicenter phase I trial. Twenty-seven patients were included in dose escalation; they received from 10 to 900 mg twice daily to establish the recommended phase II dose (RP2D) of 600 mg twice daily.

The researchers found that ulixertinib exposure was dose-proportional to the RP2D and almost completely inhibited ERK activity in whole blood. Overall, 32% of the 108 patients included in the expansion cohort required dose reduction. Diarrhea, fatigue, nausea, and dermatitis acneiform were the most common treatment-related adverse events (48, 42, 41, and 31%, respectively). Seventeen percent of 18 patients dosed at or above the maximum tolerated dose and 14% of 81 evaluable patients in dose expansion had partial responses. Patients with NRAS-, BRAF V600-, and non-V600 BRAF-mutant solid tumors had responses.

"Here, we describe the first-in-human dose-escalation study of an ERK1/2 inhibitor for the treatment of patients with advanced solid tumors," the authors write. "Ulixertinib has an acceptable safety profile with favorable pharmacokinetics and has shown early evidence of clinical activity in NRAS- and BRAF V600- and non-V600-mutant solid-tumor malignancies."

Several authors disclosed financial ties to the pharmaceutical industry.

Reference

Sullivan R, Infante JR, Janku F, et al. First-in-class ERK1/2 inhibitor ulixertinib (BVD-523) in patients with MAPK mutant advanced solid tumors: results of a phase I dose escalation and expansion study. Cancer Discov. 2017 Dec 15. doi: 10.1158/2159-8290.CD-17-1119

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