Tepotinib for Lung Cancer

Not currently recruiting at 205 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: EMD Serono Research & Development Institute, Inc.

Must not be taking: Anti-EGFR, Anti-ALK

Disqualifiers: Symptomatic brain metastases, Uncontrolled hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 66 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if tepotinib (also known as Tepmetko or EMD-1214063) can stop lung cancer from growing and spreading. It also evaluates the drug's safety, potential side effects, and impact on quality of life. The trial targets individuals with advanced lung cancer who have specific genetic changes called MET alterations and have not undergone more than two other treatments. For those with these genetic changes and advanced lung cancer, this trial might be suitable. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must not have had certain cancer treatments within 21 days before starting the trial, and you should not have uncontrolled high blood pressure or unresolved side effects from previous treatments.

Is there any evidence suggesting that tepotinib is likely to be safe for humans?

Research shows that tepotinib is generally well-tolerated by people with certain types of lung cancer. Studies have found that the side effects of tepotinib are manageable and usually do not greatly affect most patients' quality of life. One study demonstrated that the safety of tepotinib remained consistent over long-term use, with serious side effects being uncommon. While some patients experienced side effects, these were usually not severe enough to stop treatment. Overall, research suggests that tepotinib is safe for people, especially those with specific genetic changes in their cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lung cancer?

Tepotinib is unique because it specifically targets MET gene alterations, which are known drivers of certain lung cancers. Unlike standard treatments such as chemotherapy or immunotherapy, which can affect a broad range of cells, tepotinib works by inhibiting MET signaling pathways directly involved in tumor growth and survival. Researchers are excited about tepotinib because it offers a more tailored approach, potentially leading to better outcomes for patients with METex14 skipping alterations or MET amplification. This precision in targeting can also mean fewer side effects compared to more generalized treatments.

What evidence suggests that tepotinib might be an effective treatment for lung cancer?

Research has shown that tepotinib effectively treats a specific type of lung cancer called non-small-cell lung cancer (NSCLC) with MET exon 14 skipping mutations. In studies, patients taking tepotinib experienced an average of 9 months without cancer progression. On average, patients lived for 17 months, indicating a significant increase in life expectancy. Tepotinib also helped maintain a stable quality of life, with manageable side effects over time. In this trial, participants will receive tepotinib to further evaluate its effectiveness for people with this specific lung cancer mutation. These findings suggest that tepotinib could be a promising option for individuals with this mutation. ^{1 2 3 5 6}

Who Is on the Research Team?

Medical Responsible

Principal Investigator

EMD Serono Research & Development Institute, Inc, a business of Merck KGaA, Darmstadt, Germany

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that haven't had more than two prior treatments. They must have a certain gene alteration called METex14 and be in good physical condition (ECOG PS of 0 or 1). Women participating should not be pregnant or breastfeeding and must use effective contraception, as should men with female partners who could bear children.

Inclusion Criteria

I agree to use, and ensure my partner uses, effective birth control.

My lung cancer is advanced and has been confirmed by lab tests.

I am not pregnant or breastfeeding and either cannot become pregnant or agree to use effective birth control.

Exclusion Criteria

Participation in another clinical trial within the past 30 days

You have a current drug or alcohol problem, ongoing infection, or other serious health or mental issues that could make it risky for you to take part in the trial, as decided by the doctors in charge.

I am legally unable to make my own decisions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 500 mg of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event leading to discontinuation, or withdrawal of consent

66 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Pharmacogenetic Research (optional)

Optional pharmacogenetic research to understand the role of genetics in drug effectiveness

What Are the Treatments Tested in This Trial?

Interventions

• Tepotinib

Trial Overview The study tests the effectiveness of tepotinib, a drug aimed at stopping lung cancer growth and spread. It also examines how the body processes this drug, its safety profile, side effects, impact on quality of life, and includes optional genetic research to understand how genes affect drug response.

How Is the Trial Designed?

Group I: Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations Experimental Treatment 1 Intervention

Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.

Group II: Part 1: Cohort B: MET Amplification Experimental Treatment 1 Intervention

Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.

Group III: Part 1: Cohort A: METex14 Skipping Alterations Experimental Treatment 1 Intervention

Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.

Tepotinib is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Tepmetko for:

• Non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations

Approved in United States as Tepmetko for:

• Metastatic non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations

Approved in Japan as Tepmetko for:

• Non-small cell lung cancer (NSCLC) with MET alterations

Who Is Running the Clinical Trial?

EMD Serono Research & Development Institute, Inc.

Lead Sponsor

Trials

86

Recruited

22,700+

Miguel Fernández Alcalde

EMD Serono Research & Development Institute, Inc.

Chief Executive Officer

Bachelor’s Degree in Pharmacy from the University Complutense in Madrid, MBA from the University of Alcalá de Henares, Master’s Degree in Management from IESE Business School

Danny Bar-Zohar

EMD Serono Research & Development Institute, Inc.

Chief Medical Officer since 2022

MD

Merck KGaA, Darmstadt, Germany

Industry Sponsor

Trials

449

Recruited

122,000+

Danny Bar-Zohar

Merck KGaA, Darmstadt, Germany

Chief Medical Officer since 2022

MD

Belén Garijo

Merck KGaA, Darmstadt, Germany

Chief Executive Officer since 2021

MD

Published Research Related to This Trial

Tepotinib, a selective c-Met inhibitor, shows promise in overcoming resistance to first-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), particularly in models with high c-Met expression.

In various xenograft models, tepotinib combined with EGFR TKIs not only delayed tumor regrowth but also achieved complete tumor regression in certain cases, suggesting its potential as a treatment strategy for patients with acquired resistance to EGFR TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The selective c-Met inhibitor tepotinib can overcome epidermal growth factor receptor inhibitor resistance mediated by aberrant c-Met activation in NSCLC models. Friese-Hamim, M., Bladt, F., Locatelli, G., et al.[2022]

In a study involving 73 patients with advanced EGFR-mutant non-small-cell lung cancer (NSCLC), the combination of tepotinib and gefitinib showed promising efficacy, particularly in patients with high MET overexpression or MET amplification, leading to longer progression-free survival (PFS) compared to standard chemotherapy.

The treatment was generally well-tolerated, with no dose-limiting toxicities observed, although some patients experienced grade 3 or worse adverse events, such as increased amylase and lipase levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. Wu, YL., Cheng, Y., Zhou, J., et al.[2020]

Tepotinib, an oral MET inhibitor approved for treating metastatic non-small cell lung cancer, generally causes mild to moderate adverse events (AEs) such as peripheral edema, nausea, and diarrhea, which are manageable with proper care.

Proactive monitoring and early intervention, including treatment interruptions for severe AEs, are essential for effective nursing management of patients on tepotinib, ensuring better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tepotinib: Management of Adverse Events in Patients With MET Exon 14 Skipping Non-Small Cell Lung Cancer. Ahn, L., Alexander, T., Vlassak, S., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2004407

Tepotinib in Non–Small-Cell Lung Cancer with MET Exon ... We administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001124

Tepotinib in patients with MET exon 14 skipping non-small ... Tepotinib showed robust efficacy in patients with METex14 skipping NSCLC in VISION. Its long-term manageable safety profile is reflected in stable HRQOL ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.8631

Clinical outcomes of tepotinib and immune checkpoint ... ICI therapy, which was administered to 34 patients at various times, achieved a median PFS of 28.8 months (95% CI: 9.3–52.5) and a median OS of ...

4. esmoopen.com esmoopen.com/article/S2059-7029(24)01437-6/fulltext

A phase II study of tepotinib in patients with advanced solid ... For patients with non-small-cell lung cancer with METex14, the median PFS was 9 months (95% CI 4.7-13.4 months) and the median OS was 17 months ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10963552/

Modelling the Effectiveness of Tepotinib in Comparison to ... This study estimates the long-term survival and quality-adjusted life-year benefit of MET inhibitor tepotinib versus current standard of care from a UK ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9365370/

Tepotinib Efficacy and Safety in Patients with MET Exon 14 ... Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non–small cell lung cancer (NSCLC). We ...