FDA Approves Tepotinib for Metastatic Non-Small Cell Lung Cancer

The FDA has granted accelerated approval to tepotinib (Tepmetko, EMD Serono Inc) for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) who are harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.¹

According to earlier research, MET exon 14 alterations cause increased MET protein levels because they disrupt ubiquitin-mediated degradation. They occur in approximately 3% of adenocarcinomas and approximately 2% in other lung neoplasms and are thus attractive potential targets for lung cancer treatment, according to an FDA press release.²

The accelerated approval is based on overall response rate and duration, although continued approval for this indication may be contingent upon the findings of confirmatory trials. The review used the FDA’s Real-Time Oncology Review and was conducted under Project Orbis, an FDA Oncology Center of Excellence initiative.¹

The efficacy of tepotinib was demonstrated in the VISION trial, which was a multicenter, non-randomized, open label, multicohort study with 152 patients who had advanced or metastatic NSCLC with MET exon 14 skipping alterations. The participants received tepotinib 450 mg orally once daily until either disease progression or unacceptable toxicity.¹

The main outcome measures were overall response rate (ORR) and response duration. According to a press release, the 69 treatment-naïve patients had an ORR of 43% with a median response duration of 10.8 months. Among 83 previously treated patients, the ORR was 43% with a median response duration of 11.1 months.¹

In clinical trials, the most common adverse reactions occurring in 20% or more of patients were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. The drug can also cause interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity. The recommended dose is 450 mg once daily with food.¹

REFERENCES

• FDA Grants Accelerated Approval to Tepotinib for Metastatic Non-Small Cell Lung Cancer [news release]. FDA; February 3, 202 https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer?utm_medium=email&utm_source=govdelivery. Accessed February 4, 202
• Reungwetwattana T, Liang Y, Zhu V, and Ou S. The race to target MET exon 14 skipping alterations in non-small cell lung cancer: The Why, the How, the Who, the Unknown, and the Inevitable. Lung Cancer; January 2017. https://www.sciencedirect.com/science/article/pii/S016950021630527X. Accessed February 4, 2021.