Patients with advanced non–small cell lung cancer (NSCLC) and a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping had a 46.5% objective response rate to the targeted therapy drug tepotinib, as shown in a study presented during the ASCO20 Virtual Scientific Program (Abstract 9556) and published simultaneously by Paik et al in The New England Journal of Medicine.

“The success of this trial, alongside other studies on the same class of drugs, establishes MET exon 14 as an actionable target for non–small cell lung cancer,” said senior author Xiuning Le, MD, PhD, Assistant Professor of Thoracic/Head & Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, in an institutional press release. “We’re pleased to show that another group of [patients with] lung cancer may benefit from precision medicine.”

MET exon 14 skipping is a mutation that drives cancer growth and occurs in 3% to 4% of all patients with NSCLC. Patients with MET exon 14 skipping tend to be older—with a median age of 74—and typically do not have other actionable mutations with existing targeted therapy options.

VISION Trial

The study results represent cohort A of the single-arm, international phase II VISION trial, which is ongoing with additional cohorts. More than 6,700 patients with NSCLC were prescreened for MET alterations through liquid and/or tissue biopsy. A total of 152 patients with advanced NSCLC and MET exon 14 skipping were treated with tepotinib. Patients with prior treatment and/or stable brain metastasis were enrolled, and participants were treated with 500 mg of oral tepotinib daily.

The primary endpoint was objective response rate, defined as complete or partial response, according to the RECIST version 1.1 criteria and confirmed by independent review.

Results

After 9 months follow-up, the primary efficacy population of 99 patients had a 46.5% objective response rate, with a duration of response of 11.1 months.

“The median duration of response of almost 1 year is very meaningful for this patient population,” said Dr. Le. “It’s important for these elderly patients to have another treatment option other than traditional chemotherapy in oral form that can improve their quality of life for a long duration.”

Toxicities were manageable, with grade ≥ 3 treatment-related adverse events reported in 27.6% of patients. The most common side effect was peripheral edema. Eleven percent of patients discontinued treatment due to adverse events.

The study also collected patient-reported outcomes, which indicated an improvement in coughing and overall maintenance of quality of life.

Use of Liquid Biopsy in the Trial

The VISION study represents the largest MET exon 14–skipping cohort to be identified prospectively through liquid biopsy, verifying that liquid biopsy is a reliable method to detect the mutation. The study also showed that liquid biopsy was a useful tool to identify response to the drug.

Matched liquid biopsy samples were available for 51 patients at baseline and on treatment. Next-generation sequencing found 34 of those patients had a molecular response, with a complete or deep reduction of the mutation, and radiographic response was confirmed in 68% of patients who had a molecular response.

John Heymach, MD, PhD

“This study marked a major advance in that we now have a highly effective oral therapy for a group of [patients with] NSCLC that previously did not have any targeted therapy options,” said study coauthor John Heymach, MD, PhD, Chair of Thoracic/Head & Neck Medical Oncology at MD Anderson.

Tepotinib was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration in September 2019 based on early data from the VISION study. It was approved for use as the first oral targeted therapy for MET-positive NSCLC in Japan in March 2020.

Disclosure: The research was supported by Merck KGaA, Darmstadt, Germany. For full disclosures of the study authors, visit coi.asco.org.