FDA Approves First Once-daily Oral MET Inhibitor for Metastatic NSCLC

Tepotinib (Tepmetko) was FDA approved for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with mesenchymal-epithelial transition (MET) exon 14 skipping alterations, EMD Serono, the biopharmaceutical business of Merck KGaA, Darmstadt, Germany, in the US, announced today. Tepotinib’s approval marks the first for a once-daily oral MET inhibitor for this disease indication.

Tepotinib gained accelerated approval, joining an increasingly dynamic landscape for NSCLC treatment. The approval is based on overall response rate and duration of response data from the pivotal phase 2 VISION trial (NCT02862992). The drug’s continued approval may be contingent on confirmatory trials, but the indication is one with a need for therapy options, primary investigator Paul K. Paik, MD, clinical director of thoracic oncology service at Memorial Sloan Kettering Cancer Center, said in a statement.

“METex14 skipping occurs in approximately 3% to 4% of NSCLC cases, and patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis,” he said. “There is a pressing need for targeted treatments that have the potential to generate durable anti-tumor activity and improve the lives of patients with this challenging disease. Tepmetko offers an important and welcome new therapeutic option for patients with metastatic NSCLC harboring these genetic mutations.”

The ongoing VISION trial is an open-label, non-randomized, multicenter, multi-cohort, single-arm study of 152 patients with a median age of 73 years receiving tepotinib as a monotherapy for advanced or metastatic NSCLC with MET exon 14 skipping alterations. The main end point of the trial is overall response rate (ORR) as determined by a blinded independent review committee (BIRC) based on RECIST version 1.1. Duration of response (DOR) was another end point in the study.

Both treatment-naïve and previously treated patients showed an ORR of 43% ([95% CI, 32–56] and [95% CI, 33-55], respectively). Median DOR was 10.8 months in treatment-naïve patients and 11.1 months in previously treated patients. Of the treatment-naïve patients, 67% had a DOR of 6 months or more, compared with 75% of previously treated patients.

Serious adverse reactions occurred 45% of the patients receiving tepotinib, with the most common (≥20%) being edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Fatal adverse reactions occurred in 1 patient due to pneumonitis, 1 patient due to hepatic failure, and 1 patient due to dyspnea from fluid overload.

Tepotinib sets itself apart as the first and only approved METinhibitor taken orally once a day. Before its accelerated approval in the US, it was approved in Japan in March 2020, making it the first oral MET inhibitor to be approved anywhere in the world. It is administered as 2 tablets (225 mg each) for a total 450 mg dose.

“This approval of Tepmetko by the FDA is an important milestone on our mission to significantly improve the treatment of cancer where MET plays a driving role,” Danny Bar-Zohar, MD, global head of development for the health care business of Merck KGaA, said. “Our focus now is to ensure Tepmetko is accessible to patients in the United States and fully integrated into clinical practice given the important advance it represents for indicated patients as an oral once-a-day precision medicine.”

Ahead of the accelerated FDA approval, the FDA granted tepotinib breakthrough therapy designation and orphan drug designation. The drug was reviewed under the FDA Oncology Center of Excellence Real-Time Oncology Review pilot program, which aims to streamline the review process and make safe, effective treatments available to patients as early as possible.

“In recent years, the treatment of lung cancer has seen powerful progress in the understanding of the genetic mutations that lead to tumor growth, resistance and progression,” said Andrea Ferris, president and CEO of LUNGevity. “The availability of a new precision medicine for NSCLC with METex14 skipping alterations advances patient access to targeted treatment and underscores the importance of routine comprehensive biomarker testing for patients with this challenging cancer.”

Reference

FDA Approves Tepmetko as the first and only once-daily oral MET Inhibitor for patients with metastatic NSCLC with METex14 skipping alterations. News release. EMD Serono; February 3, 2021. Accessed February 3, 2021. http://media.emdserono.com/2021-02-03-FDA-approves-TEPMETKO-for-Patients-with-Metastatic-NSCLC-with-METex14-Skipping-Alterations