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Phase I Trial of Combined MEK and EGFR Inhibition in NSCLC

By: Celeste L. Dixon
Posted: Monday, August 10, 2020

The combination of the EGFR inhibitor nazartinib and the MEK inhibitor trametinib is under study in the phase I EATON trial in patients with advanced or metastatic EGFR-mutant non–small cell lung cancer (NSCLC). Jürgen Wolf, MD, of the University of Cologne, Germany, and colleagues noted that one of three patients experienced no disease progression for more than 4 months with the combination therapy; the patient had T790M-negative disease that was resistant to afatinib. The team presented its investigational findings during the 2020 American Association of Cancer Research (AACR) Virtual Annual Meeting II (Abstract CT255).

One of the three patients developed a dose-limiting toxicity (grade 3 creatinine phosphokinase elevation) with nazartinib at 100 mg daily and trametinib at 1 mg daily. The other two patients did not, so that will be the dose given to three additional patients in the next phase of the trial, according to the researchers. In addition to the patient who experienced disease stability, one other patient (who had T790M-negative disease that was resistant to osimertinib) was evaluable, and that patient experienced disease progression.

The rationale behind this study approach is that combining MEK and EGFR inhibition “may break resistance and delay treatment failure” in patients with EGFR-mutant NSCLC, explained Dr. Wolf and co-investigators. MEK inhibition “resensitized cells to EGFR-targeted treatment in preclinical models.” EGFR tyrosine kinase inhibitor treatment is generally effective initially in treating the disease, but the development of resistance—due to a variety of mechanisms—is currently inevitable, they noted.

Disclosure: The study authors’ disclosure information can be found at abstractsonline.com.



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