UK Medicines and Healthcare Products Regulatory Agency (MHRA) issues a conditional Marketing Authorisation of TEPMETKO® (tepotinib) for the treatment of advanced NSCLC with METex14 Skipping Alterations

• Tepotinib is the first MHRA authorised MET inhibitor for the treatment of adult patients with advanced NSCLC with METex14 Skipping Alterations
• In the VISION study, tepotinib demonstrated consistent and durable responses across lines of therapy and irrespective of patient characteristics
• VISION is the largest clinical study to date of patients with advanced NSCLC with MET exon 14 skipping enrolled by liquid biopsy or tissue biopsy

Merck announced today that the UK Medicines and Healthcare Products Regulatory Agency (MHRA) has granted a conditional Marketing Authorisation (CMA)¹ in Great Britain for tepotinib for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) harbouring mesenchymal-epithelial transition factor gene (MET) exon 14 (METex14) skipping alterations.²

This authorisation is based on results from the Phase II VISION study evaluating tepotinib as monotherapy in patient with advanced or metastatic NSCLC with METex14 skipping alterations, prospectively assessed by liquid biopsy or tissue biopsy. Efficacy was evaluated in 146 patients and the study demonstrated an objective response rate, the primary outcome measure, by independent review of 45.2% (95% confidence interval [CI], 37.0 to 53.6) in the combined-biopsy group.² Data from the primary analysis of the VISION study were published in The New England Journal of Medicine (NEJM) on 29 May 2020.³

Lung cancer is the third most common cancer in the UK, with over 47,000 people diagnosed every year (2015-2017), and was the leading cause of cancer related death in the UK in 2018.^4,5 NSCLC is the most common type of lung cancer and accounts for approximately 80-85% of all lung cancer diagnoses in the UK.⁶ METex14 alterations occur in approximately 3-4% of NSCLC cases and generally exhibit a poorer clinical prognosis compared with other types of NSCLC.⁷

“We welcome the decision by the MHRA to authorise the targeted therapy, tepotinib. Lung cancer can be an aggressive, hard-to-treat cancer so it is vital we have as many treatment options available to patients so they can live well with this disease for as long as possible. This decision takes us a step closer to having another treatment for people in this country who are living with non-small cell lung cancer,” said Paula Chadwick, Chief Executive, Roy Castle Lung Cancer Foundation.

“This is the first MHRA authorised MET inhibitor to be made available to eligible patients, and as such would have a significant impact on their current clinical outcomes. This authorisation is an important advancement for patients with METexon14 skipping aberrations and represents a significant step forward in the development of new targeted therapies in advanced NSCLC,” said Professor Sanjay Popat, Consultant Thoracic Medical Oncologist, The Royal Marsden NHS Foundation Trust.

Dr Stuart Hill, Medical Director, Merck UK & Ireland said: “Merck is delighted to have received MHRA authorisation for tepotinib, a novel MET targeted oral therapy for adult patients with advanced non-small cell lung cancer. Tepotinib targets rare MET exon 14 skipping mutations and is the first therapy of this kind to be granted a GB marketing authorisation. This authorisation means that eligible patients, who typically have a poor prognosis, now have an additional treatment option available to them.”

Tepotinib has been authorised under a ‘conditional approval’ scheme. This means that further evidence on this medicinal product is awaited. 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, including the UK’s MHRA. It aims to deliver faster patient access to innovative cancer treatments with potential benefits over existing therapies across the globe. Applications submitted to the MHRA within a Project Orbis procedure are national (Great Britain only) marketing authorisation applications and variations.⁸

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 About lung cancer

Lung cancer is the third most common cancer in the UK, with over 47,000 people diagnosed every year (2015-2017), and the leading cause of cancer related death in the UK in 2018.^4,5 There are 2 main forms of primary lung cancer: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). NSCLC is more common and accounts for approximately 80-85% of all lung cancer diagnoses in the UK.⁶ Due to the non-specific symptoms of NSCLC, 75% of the patients are diagnosed at stage III or IV where outcomes are particularly poor,⁹ with respective 1-year survival rates of 48.7% and 19.3% and 5-year survival rate of 12.6% and 2.9% in adults diagnosed between 2013 - 2017.¹⁰

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 under the brand name TEPMETKO®.¹¹ Tepotinib was approved in the United States in February 2021¹² for the treatment of adult patients with metastatic NSCLC harbouring mesenchymal-epithelial transition (MET) exon 14 skipping alterations under the brand name TEPMETKO®. This indication is approved under accelerated approval based on overall response rate and duration of response. Tepotinib is currently under regulatory review by the European Medicines Agency (EMA).

About the VISION Study²

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=146). 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 45.2% (95% confidence interval [CI], 37.0 to 53.6), with a median duration of response of 11.1 months (95% CI, 8.4 to 18.5) in the combined-biopsy group.
• 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.^13,14

The safety data described reflect exposure to tepotinib 450 mg once daily in 255 patients with advanced NSCLC harbouring METex14 skipping alterations included in the VISION study. Median duration of treatment was 22.3 weeks (range: 0 to 188 weeks).

Serious adverse events occurred in 45% of patients who received tepotinib. 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 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 2020, Merck generated sales of € 17.5 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. Gov.uk. Conditional Marketing Authorisations, exceptional circumstances Marketing Authorisations and national scientific advice. Available from: https://www.gov.uk/guidance/conditional-marketing-authorisations-exceptional-circumstances-marketing-authorisations-and-national-scientific-advice. [Accessed September 2021].
2. GB Summary of Product Characteristics TEPMETKO® SmPC 2021
3. Paik PK et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med 2020 May 29; [e-pub]. (https://doi.org/10.1056/NEJMoa2004407).
4. Cancer Research UK. Lung cancer statistics. Available at: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer#heading-Zero [Accessed September 2021]
5. Lung cancer – NHS. Available at: Lung cancer - NHS (www.nhs.uk) [Accessed September 2021]
6. Cancer Research UK. Types of Lung Cancer. Available at: https://www.cancerresearchuk.org/about-cancer/lung-cancer/stages-types-grades/types [Accessed September 2021].
7. Wolf J, et al. EORTC/NCI/AACR 2018. Poster 403.
8. Gov.uk. Guidance on Project Orbis. Available at: https://www.gov.uk/guidance/guidance-on-project-orbis. [Accessed September 2021].
9. Knight S et al. Progress and prospects of early detection in lung cancer. Open Biol. 2017; 7(9): 170070.
10. Cancer Research UK - Lung Cancer Survival Statistics Available from: https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/lung-cancer/survival#heading-Three [Accessed September 2021]
11. Press Releases. TEPMETKO (tepotinib) Approved in Japan for Advanced NSCLC with METex14 Skipping Alterations. Available at: https://www.merckgroup.com/en/news/tepotinib-25-03-2020.html. [Accessed September 2021]. 
12. Press Releases. FDA Approves TEPMETKO® as the First and Only Once-daily Oral MET Inhibitor for Patients with Metastatic NSCLC with METex14 Skipping Alterations. Available at: https://www.merckgroup.com/en/news/tepotinib-fda-approval-metex14-03-02-2021.html. [Accessed September 2021].
13. Patel, J.D. et al. Intracranial activity of tepotinib in patients with MET exon 14 skipping NSCLC enrolled in VISION. Presented at the American Society of Clinical Oncology (ASCO) annual meeting. June 4 – 8 2021.
14. Garassino, M. et al. Efficacy and safety of tepotinib in patients with advanced age: VISION subgroup analysis of patients with MET exon 14 skipping NSCLC. Presented at the European Society for Medical Oncology (ESMO) annual meeting. 16-21 September 2021.