Tepotinib + Osimertinib for Non-Small Cell Lung Cancer

Recruiting at 179 trial locations

Overseen By Communication Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: EMD Serono Research & Development Institute, Inc.

Must be taking: Osimertinib

Must not be taking: Steroids

Disqualifiers: Brain metastasis, Impaired cardiac function, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 42 months

140 Participants Needed

Trial Summary

What is the purpose of this trial?

This study was to assess the antitumor activity, safety, tolerability, and pharmacokinetics (PK) of the Mesenchymal-epithelial Transition Factor (MET) inhibitor tepotinib combined with the 3rd generation EGFR inhibitor osimertinib in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants should not have unresolved side effects from previous cancer treatments, except for hair loss.

What data supports the effectiveness of the drug combination Tepotinib and Osimertinib for treating non-small cell lung cancer?

Osimertinib is effective in treating non-small cell lung cancer with specific mutations, as it significantly prolongs the time patients live without the cancer getting worse compared to older treatments. It is particularly useful for patients who have developed resistance to earlier treatments. ^{1 2 3 4 5}

What is the safety profile of Osimertinib for non-small cell lung cancer?

Osimertinib has been studied in patients with non-small cell lung cancer, and common side effects include diarrhea, rash, dry skin, and nail problems. Serious side effects occurred in about 28% of patients, and 5.6% stopped treatment due to these effects. ^{1 5 6 7 8}

What makes the drug combination of Tepotinib and Osimertinib unique for treating non-small cell lung cancer?

The combination of Tepotinib and Osimertinib is unique because it targets specific mutations in non-small cell lung cancer (NSCLC), with Osimertinib focusing on the EGFR T790M mutation, which is a common cause of resistance to previous treatments, while Tepotinib may help address other resistance mechanisms, potentially improving treatment effectiveness. ^{1 2 3 9 10}

Research Team

Medical Responsible

Principal Investigator

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Eligibility Criteria

This trial is for adults with advanced non-small cell lung cancer (NSCLC) who have an EGFR mutation and MET amplification. They must have only received osimertinib previously, shown resistance to it, and be in good physical condition (ECOG 0 or 1). Patients with a history of certain lung diseases, uncontrolled hypertension, brain metastasis requiring steroids, or inadequate organ function cannot participate.

Inclusion Criteria

My cancer progressed after initially responding to osimertinib treatment.

My lung cancer has a specific EGFR mutation.

My cancer has MET amplification confirmed by specific tests.

Exclusion Criteria

I have had lung conditions that needed steroid treatment.

My high blood pressure is not controlled, even with medication.

Other protocol defined exclusion criteria could apply

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tepotinib and Osimertinib until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal

Up to 42 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 42 months

Treatment Details

Interventions

• Osimertinib
• Tepotinib

Trial Overview The study tests the combination of two drugs: Tepotinib (a MET inhibitor) and Osimertinib (an EGFR inhibitor), in patients whose NSCLC has worsened after treatment with Osimertinib alone. It aims to evaluate the effectiveness and safety profile of this drug combo.

Participant Groups

Group I: Tepotinib and Osimertinib Experimental Treatment 2 Interventions

Participants received a single oral dose of Tepotinib 500 milligrams (mg) followed by Omisertinib 80 mg once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.

Group II: Tepotinib Mono-therapy Experimental Treatment 1 Intervention

Participants received a single oral dose of Tepotinib 500 mg until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.

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

Approved in United States as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

Approved in European Union as Tagrisso for:

• Locally advanced or metastatic non-small-cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R mutations
• Metastatic EGFR T790M mutation-positive NSCLC

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 of 94 patients with advanced non-small-cell lung cancer (NSCLC) who had previously been treated, osimertinib showed a 47.3% overall objective response rate and a 90.1% disease control rate, indicating its effectiveness in this population.

Patients with the T790M mutation experienced significantly longer progression-free survival (PFS) compared to those without the mutation, highlighting osimertinib's targeted efficacy, especially in those with specific genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. Mu, Y., Xing, P., Hao, X., et al.[2022]

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor specifically designed to target the EGFR T790M mutation, which is a common cause of resistance to first-line EGFR TKIs in advanced non-small-cell lung cancer.

This review highlights the efficacy of osimertinib in clinical trials, demonstrating its ability to effectively treat patients with non-small-cell lung cancer harboring the T790M mutation while minimizing effects on normal EGFR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib making a breakthrough in lung cancer targeted therapy. Zhang, H.[2020]

Osimertinib is an oral medication specifically designed to target the EGFR T790M mutation in advanced non-small cell lung cancer (NSCLC), which helps overcome resistance to previous EGFR TKI therapies.

It received accelerated approval in the USA in November 2015 for patients with metastatic EGFR T790M mutation-positive NSCLC who have progressed after EGFR TKI treatment, and is currently undergoing further development for broader treatment applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib: First Global Approval. Greig, SL.[2022]

Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that effectively targets specific mutations in advanced non-small cell lung cancer (NSCLC), including the T790M mutation, leading to significantly longer progression-free survival compared to first-generation EGFR TKIs like erlotinib or gefitinib.

The benefits of osimertinib in prolonging progression-free survival were consistent across all patient groups, regardless of the type of EGFR mutation or the presence of CNS metastases, and it has a generally manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. Scott, LJ.[2020]

Osimertinib (Tagrisso) is a targeted therapy approved by the FDA for patients with metastatic non-small cell lung cancer (NSCLC) who have the EGFR T790M mutation and have progressed after previous treatments.

The drug received special designations from the FDA, including breakthrough therapy and priority review, highlighting its significance in treating resistant forms of NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Skoulidis, F., Papadimitrakopoulou, VA.[2022]

Osimertinib (TAGRISSO) received accelerated FDA approval for treating metastatic non-small cell lung cancer with the EGFR T790M mutation, showing significant tumor response rates of 57% and 61% in two major trials involving 411 patients.

While osimertinib demonstrated promising efficacy, common side effects included diarrhea (42%) and rash (41%), with 28% of patients experiencing severe adverse events, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. Khozin, S., Weinstock, C., Blumenthal, GM., et al.[2022]

In a phase 2 study involving 210 patients with EGFR Thr790Met-positive non-small-cell lung cancer (NSCLC), osimertinib demonstrated significant efficacy, with 70% of patients achieving an objective response, including 3% with complete responses.

Osimertinib was found to have manageable side effects, although serious adverse events occurred in 25% of patients, with interstitial lung disease being the only fatal event possibly related to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Goss, G., Tsai, CM., Shepherd, FA., et al.[2022]

Osimertinib significantly improves progression-free survival (PFS) in patients with metastatic non-small cell lung cancer (NSCLC) with the EGFR T790M mutation, showing a median PFS of 10.1 months compared to 4.4 months with chemotherapy in a trial of 419 patients.

The safety profile of osimertinib is favorable compared to other EGFR tyrosine kinase inhibitors and chemotherapy, with common side effects including diarrhea and rash, making it a viable treatment option for patients who have progressed on previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. Odogwu, L., Mathieu, L., Goldberg, KB., et al.[2022]

Osimertinib (AZD9291) is effective in prolonging survival for non-small cell lung cancer patients with EGFR mutations, but resistance to the drug is a common issue, prompting the need to explore resistance mechanisms.

In this study, AZD9291-resistant NSCLC cell lines were established, revealing significant changes in circular RNA (circRNA) expression profiles, which may contribute to drug resistance and could serve as potential targets for future gene therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. Chen, T., Luo, J., Gu, Y., et al.[2022]

References

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

Real-World Data Of Osimertinib In Patients With Pretreated Non-Small Cell Lung Cancer: A Retrospective Study. [2022]

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

Osimertinib making a breakthrough in lung cancer targeted therapy. [2020]

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

Osimertinib: First Global Approval. [2022]

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

Osimertinib as first-line therapy in advanced NSCLC: a profile of its use. [2020]

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

Targeting the Gatekeeper: Osimertinib in EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

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

Osimertinib for the Treatment of Metastatic EGFR T790M Mutation-Positive Non-Small Cell Lung Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. [2022]

8. England pubmed.ncbi.nlm.nih.gov

FDA Benefit-Risk Assessment of Osimertinib for the Treatment of Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor T790M Mutation. [2022]

9. Singapore pubmed.ncbi.nlm.nih.gov

Comprehensive analysis of circular RNA profiling in AZD9291-resistant non-small cell lung cancer cell lines. [2022]

10. Singapore pubmed.ncbi.nlm.nih.gov

Activation of insulin-like growth factor-1 receptor confers acquired resistance to osimertinib in non-small cell lung cancer with EGFR T790M mutation. [2022]