News Release

NICE recommends Merck’s TEPMETKO® (tepotinib) as the first oral MET inhibitor treatment as an option for adult patients with advanced NSCLC with METex14 skipping alterations

Business Announcement

Merck KGaA, Darmstadt, Germany

PRESS RELEASE FOR UK BASED MEDICAL AND HEALTHCARE JOURNALISTS

14 April 2022, Feltham (Merck) - Today Merck, a leading science and technology company, announced that the National Institute for Health and Care Excellence (NICE) has recommended TEPMETKO® (tepotinib), which is approved for the treatment of adult patients in Great Britain with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations.1

Tepotinib is the first and only oral MET inhibitor to be recommended for the treatment of adult patients with advanced NSCLC harbouring METex14 skipping alterations for use on the NHS in England, Wales and Northern Ireland.  Interim funding via the Cancer Drugs Fund will enable reimbursement of tepotinib in England until NICE final guidance is published and funded after a 30-day mandatory period. In Northern Ireland, tepotinib was approved via the European Medicines Agency (EMA) marketing authoritisation in February 2022 and access for eligible patients will be in line with this authorisation.

Dr Shobhit Baijal, Consultant Medical Oncologist, University Hospital Birmingham NHS Trust explains: “Existing treatment options for patients with METex14 skipping mutations have generally shown limited progression-free survival and overall survival benefits. Tepotinib is a new targeted therapy and the first MET inhibitor to be made available for eligible patients.  It is a significant step forward in the treatment of adult advanced NSCLC patients with METex14 skipping alterations and has demonstrated its clinical benefits for this aggressive type of lung cancer. Treatment involves identifying a genomic biomarker to be able to provide this new potential treatment option.”

NSCLCs with MET alterations are generally associated with poorer clinical prognosis compared to NSCLCs without MET alterations, with a lower median overall survival observed when compared to NSCLC patients without the alteration.2 The presence of these genetic alterations has been recognised as an important therapeutic target for personalised treatment,5 which can be identified via a tissue sample.

“It is excellent news to hear that NICE has approved tepotinib for people with non-small cell lung cancer and MET alterations. This is an aggressive type of lung cancer so we welcome any and all new treatments that could give patients a chance to live longer and live well with this disease. It is vital all patients have access to more targeted treatments for their specific type of lung cancer and that they undergo genomic testing. That way, they can benefit from the new therapies, like tepotinib, that are now available to them,” said Paula Chadwick, Chief Executive, Roy Castle Lung Cancer Foundation.

Targeted treatments, like tepotinib, require genomic testing to determine which patients are eligible. To enable advanced genomic testing, the NHS is in the process of developing Genomic Laboratory Hubs (GLH) across the UK,6,7 which are equipped with novel technology to manage more complex tests that cannot be completed at other laboratory sites. These hubs perform comprehensive genomic assessments on patients, providing detailed information about their cancer, allowing their clinician to select the most appropriate and targeted treatment available for them. The tests carried out in England are determined by the 2021/2022 National Genomic Test Directory,8 which is commissioned by the NHS; METex14 skipping is expected to be included in the forthcoming testing directory update.

Doina Ionescu, General Manager, Merck says: “We are committed to our vision for the future of medicine – moving away from a ‘one size fits all’ approach that is now the norm for many diseases to a focus on personalised medicines and the development of innovative targeted treatments, like tepotinib. As the first therapy of its kind to be recommended by NICE, tepotinib has shown to help slow disease progression and prolong survival in patients with this gene mutation. Importantly, the NHS is also making progress in the screening of lung cancer patients with these types of specific gene mutations, helping to identify those patients who are most likely to benefit from this treatment.”

The pivotal clinical trial underpinning this NICE appraisal is the Phase II VISION study evaluating tepotinib as monotherapy in adult patients with advanced or metastatic NSCLC with METex14 skipping alterations, prospectively assessed by liquid biopsy or tissue biopsy.4

The VISION study has demonstrated significant benefits for patients with advanced NSCLC with METex14 skipping enrolled by liquid biopsy or tissue biopsy.4 In the VISION study, efficacy was evaluated in 275 patients and the study demonstrated an objective response rate, the primary outcome measure, by independent review of 49.1% (95% confidence interval [CI], 43.0-55.2) in the combined-biopsy group.9 The median progression-free survival was 10.8 months (95% CI: 8.5-12.4), and the median overall survival was 19.7 months (95% CI: 15.6-22.1), with results consistent between previously untreated and previously treated patients.9 These results are from a data cut-off date of February 2021.

Through the Medicines and Healthcare Products Regulatory Agency (MHRA) Early Access to Medicines Scheme (EAMS) and subsequent extensions to the scheme, eligible patients have already been initiated on treatment with tepotinib throughout the UK. This means that these patients have been able to benefit from treatment prior to NICE approval and furthermore, many oncologists now have real world clinical experience on how to prescribe tepotinib and manage patients with METex14 skipping mutations to optimise outcomes. Tepotinib is also under review by the Scottish Medicines Consortium (SMC) in Scotland and a decision is expected in Q2 2022.

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Tel: + 447342 712274

 

 

Notes to Editors

About Tepotinib

Tepotinib is a highly selective oral MET inhibitor that inhibits the oncogenic MET receptor signalling caused by MET (gene) alterations. Discovered and developed in-house at Merck, tepotinib has the potential to improve outcomes in NSCLC that have poor prognosis that harbour these specific alterations.

 

Tepotinib was the first oral MET inhibitor to receive a regulatory approval anywhere in the world for the treatment of advanced NSCLC harbouring MET gene alterations, with its approval in Japan in March 2020. Tepotinib was approved in the United States in February 2021 for the treatment of adult patients with metastatic NSCLC harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations. This indication is approved under accelerated approval based on overall response rate and duration of response. In February 2022, the European Commission approved tepotinib as monotherapy for the treatment of adult patients with advanced NSCLC harbouring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping, who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy. Northern Ireland will follow this marketing authorisation by the European Medicines Agency (EMA) for tepotinib. Tepotinib was granted a conditional Marketing Authorisation (CMA) in Great Britain in September 2021 by the UK Medicines and Healthcare Products Regulatory Agency (MHRA). The authorisation was conducted through Project ORBIS, which is coordinated by the US Food and Drug Administration (FDA), which reviews and approves promising cancer treatments concurrently with regulatory authorities in six other countries. 

 

 

Tepotinib Safety Profile10

The special warnings and precautions for use for tepotinib monotherapy include Interstitial lung disease (ILD) or ILD-like adverse reactions including pneumonitis, increase of Liver enzymes (ALT and AST), and embryo-foetal toxicity.

 

The most common adverse reactions (≥ 1/10) in people exposed to tepotinib at the recommended dose in the target indication are hypoalbuminaemia, nausea, diarrhoea, abdominal pain, constipation, vomiting, increase in ALT, oedema, fatigue/asthenia, and increase in creatinine. Serious adverse events occurred in 45% of patients who received tepotinib (N=255; cut-off date: July 2020). The most common serious adverse events (≥ 2%) included pleural effusion (6.7%), pneumonia (4.7%), dyspnoea (3.9%), general health deterioration (3.5%), peripheral oedema (2.4%), generalised oedema (2.0%), musculoskeletal pain (2.0%) and pulmonary embolism (2.0%).

 

About lung cancer

Every year around 48,500 people in the UK are diagnosed with lung cancer of which an estimated 52.7% are diagnosed with advanced (stage IIIB/C and IV) disease.11 It is the leading cause of cancer related death in the UK.12,13 NSCLC is the most common type of lung cancer and accounts for more than 87% of all lung cancer diagnoses in total.14 Respective 1-year survival rates for stage IIIB and IV NSCLC are 48.7% and 19.3% and respective 5-year survival rates are 12.6% and 2.9% in adults.15,16 METex14 alterations occur in approximately 3 to 4% of advanced NSCLC cases and generally have a poorer clinical prognosis compared with other types of NSCLC.3

 

About MET and MET exon 14 skipping alterations

The MET gene (on chromosome 7) contains instructions to build the MET protein,17 which is an important part of embryonic development, tissue regeneration, and wound healing.18 The MET protein is part of a tyrosine kinase receptor, which acts as an ‘on off’ switch for cellular growth and division.18

 

There are various possible issues with this MET protein, such as the exon 14 skipping mutation. This means that exon 14, or a piece of the code to build the protein, is skipped during the process. Exon 14 has an important role in facilitating the breakdown of the MET protein (as part of its normal lifecycle), and this mutation leads to the MET protein living longer than it should, resulting in excessive signalling and extended cell division.18 This makes the mutation a strong oncogenic driver,19 which promotes tumour proliferation, growth, and metastasis.2

 

About the VISION Study9

The Phase II VISION study (NCT02864992) is an ongoing, multicentre, single-arm, open-label study investigating tepotinib as monotherapy in adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring METex14 skipping alterations (n=275). The primary outcome measure was objective response (complete response or partial response) according to Response Evaluation Criteria in Solid Tumours (RECIST v1.1) as evaluated by an Independent Review Committee (IRC). Secondary outcome measures included duration of response, progression-free survival assessed by IRC and overall survival.

  • The response rate by independent review was 49.1% (95% confidence interval [CI], 43.0 to 55.2), with a median duration of response of 13.8 months (95% CI, 9.9 to 19.4) in the combined-biopsy group, from a data cut-off date of February 2021.
  • Efficacy outcome was independent of the testing modality (liquid biopsy or tumour biopsy) used to establish the METex14 skipping status. Consistent efficacy results in subgroups by prior therapy, presence of brain metastasis or age were observed. 

 

The safety data described reflect exposure to tepotinib 450 mg once daily in 291 patients with advanced NSCLC harbouring METex14 skipping alterations included in the VISION study, from a data cut-off date of February 2021. Median duration of treatment was 22.3 weeks (range: 0 to 188 weeks).20

 

Most common treatment-related adverse events in the VISION study (≥10%) were peripheral oedema (60.1%), nausea (22.7%), diarrhoea (21.3%), blood creatinine increase (19.6%), and hypoalbuminaemia (18.9%).

 

About Merck

Merck, a leading science and technology company, operates across healthcare, life science and electronics. Around 58,000 employees work to make a positive difference to millions of people’s lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is everywhere. In 2021, Merck generated sales of € 19.7 billion in 66 countries.

 

Scientific exploration and responsible entrepreneurship have been key to Merck’s technological and scientific advances. This is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United States and Canada, where the business sectors of Merck operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD Electronics.

 

References

  1. NICE. Final Appraisal Document. Tepotinib for treating advanced non-small-cell lung cancer with MET gene alterations [ID3761]. Available at: https://www.nice.org.uk/guidance/indevelopment/gid-ta10630/documents. [Accessed April 2022]
  2. Tong JH et al. MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non-Small Cell Lung Carcinoma with Poor Prognosis. Clin Cancer Res 016; 22:3048–3056
  3. Santarpia, et al. A narrative review of MET inhibitors in non-small cell lung cancer with MET exon 14 skipping mutations. Transl Lung Cancer Res. 2021 Mar; 10(3): 1536–1556.
  4. Paik PK et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020 May 29.
  5. Shah R, et al. MET Exon 14 skipping alterations in NSCLC. Current understanding and therapeutic advances. Available at: https://touchoncology.com/lung-cancer/journal-articles/met-exon-14-skipping-alterations-in-nsclc-current-understanding-and-therapeutic-advances/. [Accessed April 2022]
  6. NHS. Genomic Laboratory Hubs. Available at: https://www.england.nhs.uk/genomics/genomic-laboratory-hubs/. [Accessed April 2022]
  7. NHS. Genomic Medicine Service. Available at: https://www.england.nhs.uk/genomics/nhs-genomic-med-service/.  [Accessed April 2022]
  8. NHS. The National Genomic Test Directory. [online] Available at: https://www.england.nhs.uk/genomics/the-national-genomic-test-directory/ [Accessed April 2022].
  9. Cui W et al. Tepotinib in patients with MET exon 14 skipping NSCLC: Results from the VISION study and local UK experience. 20th BTOG Annual Conference (virtual). January 27-28, 2022.
  10. Electronic medicines compendium (emc). 2021. TEPMETKO 225 mg film-coated tablets SmPC. Available at: https://www.medicines.org.uk/emc/product/12970/smpc#gref [Accessed April 2022]
  11. Royal College of Physicians. National Lung Cancer Audit annual report 2020 England Data. Available at: https://www.rcplondon.ac.uk/projects/outputs/nlca-annual-report-2022 [Accessed April 2022]
  12. Cancer Research UK. Lung cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-One  [Accessed April 2022]
  13. Cancer Research UK. Cancer mortality for common cancers. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/mortality/common-cancers-compared#heading-Zero [Accessed April 2022]
  14. NHS. Overview: Lung cancer. Available at: https://www.nhs.uk/conditions/lung-cancer/ [Accessed April 2022]
  15. Cancer Research UK - Lung Cancer Survival Statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/survival#heading-Three [Accessed April 2022]
  16. Office for National Statistics. 2019. Dataset. Cancer survival in England - adults diagnosed. 2013-2017 edition. Available at: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancersurvivalratescancersurvivalinenglandadultsdiagnosed [Accessed April 2022]
  17. MET Crusaders. What is MET? Available at: https://metcrusaders.org/what-is-met/ [Accessed April 2022]
  18. Socinski, M.A, et al. MET Exon 14 Skipping Mutations in Non–Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations. JCO Precision Oncology. 2021 Apr; No 5. 653-63.
  19. Roth, et al. Prolonged survival and response to tepotinib in a non-small-cell lung cancer patient with brain metastases harboring MET exon 14 mutation: a research report. Cold Spring Harb Mol Case Stud. 2020 Dec; 6(6): a005785.
  20. Remi Veillon , et. al. Safety of Tepotinib in Patients with MET Exon 14 Skipping NSCLC and Recommendations for Management, Clinical Lung Cancer (2022), doi: https://doi.org/10.1016/j.cllc.2022.03.002

Job no:  UI-TEP-00019

Date of preparation: April 2022

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