FDA Approves Tepotinib for Metastatic Non-Small Cell Lung Cancer – A Breakthrough for Patients With A Specific Mutation

Creator: Liz Neporent
Published: 2024-02-19T09:09:01-05:00

Liz Neporent

Details

Tepotinib for Metastatic Non-Small Cell Lung Cancer

FDA fully approves tepotinib (Tepmetko) for advanced NSCLC with specific MET exon 14 mutation, impacting 3-4% of patients.
Tepotinib, a precision medicine, effectively targets and inhibits the MET protein engine, critical for cancer growth.
Early VISION trial results show significant improvement, with over half of new patients responding positively to treatment.
Full approval based on expanded data and extended follow-up, highlighting Tepotinib’s role in advancing lung cancer treatment.

The US Food and Drug Administration (FDA) fully approved the drug tepotinib (brand name, Tepmetko made by EMD Serono, Inc.) for adults with a type of advanced lung cancer known as non-small cell lung cancer (NSCLC) that has a specific genetic mutation.

NSCLC is the most common type of lung cancer, accounting for about 85% of all cases diagnosed in the U.S. Tepotinib targets a mutation known as the MET exon 14 skipping alterations that only occurs in 3-4% of NSCLC patients, or around 8,000 patients a year in the U.S.

”While it is a small fraction, thousands of patients could benefit given how common and serious lung cancer can be,” Dr. Balazs Halmos, MD, MS, associate director, Clinical Science, and director, Thoracic Oncology, at Montefiore Einstein Comprehensive Cancer Center explains to SurvivorNet.

Doctors find the mutation by analyzing the cancer’s DNA from a tissue biopsy or a blood sample. Then they use advanced genetic testing to identify this specific change among the many genes in cancer cells.

“Also, there are other biomarkers that can help patients receive similar medicines, expanding the percentage of patients who can benefit from biomarker testing and targeted therapies, so a key message is to ensure that what is called expanded biomarker testing is done for basically all non-small cell lung cancer patients,” Dr. Halmos says.

Understanding MET exon 14 skipping mutation

Dr. Halmos explains MET exon 14 skipping like this:

“We need to imagine that our cells all have little engines that make them work, but there are appropriate pedals/brakes to get the right balance to prevent aberrant/cancerous growth. MET is a protein that is one of these engines.”

“ In some lung cancer cells this engine suffers an error. One of its parts is skipped, and this part, called “exon 14,” basically includes a key brake. Without it the MET protein can now run awry leading to cancer growth.”

Tepotinib is a unique, “precision medicine” that treats this mutation, Dr. Halmos notes. It does not fix the brake caused by the skip mutation, he says. Instead, it shuts down the overall MET protein engine in cancers where the MET protein is the driver.

Scientific findings

Tepotinib, which belongs to a class of drugs known as tyrosine kinase inhibitors, received a conditional approval in 2021, based on early results from the VISION clinical tria l published in the New England Journal of Medicine.

In the VISION trial, patients treated with tepotinib at 450 mg daily with food showed significant improvement.

57% of patients new to treatment responded positively
40% of those patients maintained the response for a year or more.
45% of patients who were previously treated with another drug responded positively to Tepmetko
36% of those patients had a sustained response for at least a year.

“While it was not specifically compared to conventional chemo or immunotherapy, the results are impressive and are felt to compare favorably to other chemo or immunotherapy based options,” Dr. Halmos says. “At minimum, tepotinib adds an extra option for our patients.”

Common side effects included swelling, nausea, fatigue, muscle pain, diarrhea, difficulty breathing, reduced appetite, and rash.

The full approval was supported by additional data from 161 more patients and an extended follow-up period of 28 months, affirming tepotinib’s benefit.

The drug’s development was fast-tracked due to its potential as a significant advancement in treating this specific lung cancer variant.

What’s next

Targeted medicines such as tepotinib tend to have fewer side effects and more activity than conventional chemotherapy. It kills cancerous cells while leaving surrounding healthy cells alone.

It’s an important treatment advancement, notes Dr. Halmos.

“…targeted medicines such as tepotinib are continuing to transform the landscape for our patients with advanced and now also earlier stage lung cancer. With optimal use of biomarker testing and tailored targeted and immunotherapies, a larger and larger fraction of our patients with lung cancer can benefit from more effective and less toxic therapies.” Dr. Halmos says.

What is NSCLC

Each year, over 200,000 people in the U.S. are diagnosed with lung cancer, meaning roughly 170,000 cases are NSCLC, according to American Cancer Society statistics. This type of cancer grows more slowly than other types of the disease.

Doctors use various treatments like surgery, radiation, and medication to fight NSCLC.