Tepotinib for Lung Cancer

Recruiting at 156 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

337 Participants Needed

Trial Summary

What is the purpose of this trial?

This study looked at how effective the study drug (tepotinib) was at stopping the growth and spread of lung cancer. This study also measures a number of other things including safety of the study drug and the side effects, how body processes the study drug, or how the study drug affects your quality of life. The study also has an optional pharmacogenetic research part. Pharmacogenetic research is an important way to try to understand the role of genetics in human disease and how genes impact the effectiveness of drugs, because differences in genes can change the way a person responds to a particular drug.

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.

What data supports the effectiveness of the drug Tepotinib for lung cancer?

Tepotinib has shown effectiveness in treating non-small cell lung cancer (NSCLC) with specific genetic changes (MET alterations), leading to its approval in Japan and the U.S. It has been found to overcome resistance to other cancer drugs in certain lung cancer models, making it a promising option for patients with these specific cancer types. ^{1 2 3 4 5}

What is known about the safety of Tepotinib for lung cancer?

Tepotinib has been evaluated for safety in patients with non-small-cell lung cancer (NSCLC) and is generally considered safe, though like many cancer treatments, it may have side effects. Studies have shown it to be a selective MET inhibitor, and safety data from trials suggest it is well-tolerated in humans. ^{1 6 7 8 9}

What makes the drug Tepotinib unique for treating lung cancer?

Tepotinib is unique because it is an oral drug specifically designed to target and inhibit the MET protein in non-small cell lung cancer (NSCLC) patients with MET alterations, such as MET exon 14 skipping mutations. This makes it particularly effective for patients who have developed resistance to other treatments, like EGFR inhibitors. ^{1 2 4 5 10}

Research Team

Medical Responsible

Principal Investigator

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

Eligibility Criteria

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

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.

Participation in another clinical trial within the past 30 days

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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]

References

1. England 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. [2020]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Tepotinib: Management of Adverse Events in Patients With MET Exon 14 Skipping Non-Small Cell Lung Cancer. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Tepotinib: First Approval. [2020]

5. Spain pubmed.ncbi.nlm.nih.gov

Tepotinib hydrochloride for the treatment of non-small cell lung cancer. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. [2021]

7. Germany pubmed.ncbi.nlm.nih.gov

Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations. [2022]

8. Ireland pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and anti-tumor activity of olmutinib in non-small cell lung cancer with T790M mutation: A single arm, open label, phase 1/2 trial. [2020]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Toxicity profile of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung cancer: A systematic review and network meta-analysis. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

SHP2 Inhibition Influences Therapeutic Response to Tepotinib in Tumors with MET Alterations. [2020]