Novartis : announces NEJM publication of pivotal study of Tabrecta™ in patients with METex14 metastatic non-small cell lung cancer

• Tabrecta™ (capmatinib, formerly INC280) is the first and only therapy approved by the FDA to specifically target metastatic non-small cell lung cancer (NSCLC) with a mutation that leads to MET exon 14 skipping (METex14)

• METex14 is an important biomarker for physicians to consider when selecting metastatic NSCLC treatment options¹
  
• In the US, METex14 metastatic NSCLC is diagnosed in ~4,000-5,000 patients annually and typically indicates aggressive disease with a poor prognosis^2-3

Basel, September 2, 2020 - Data from the pivotal GEOMETRY mono-1 Phase II study published today in The New England Journal of Medicine (NEJM) show treatment with Tabrecta™ (capmatinib, formerly INC280) resulted in positive overall response rates (ORR) among adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to skipping of MET exon 14 (METex14)¹. Positive duration of response (DOR) was also observed¹. The presence of METex14 is a viable selection strategy for metastatic lung cancer patients who may be eligible for Tabrecta, thereby underscoring the importance of broad molecular testing for NSCLC patients¹.

MET, a receptor tyrosine kinase coded by the MET gene, normally plays an important role in cell signaling, proliferation, and survival⁴. Many cancers are associated with abnormal signaling through the MET receptor pathway, caused by multiple mechanisms including point mutations, insertions/deletions that lead to skipping of exon 14⁴. Until recently, one obstacle to effectively targeting MET has been the identification of an optimal biomarker, however, METex14 has emerged as a predictive biomarker for MET-directed therapies, such as Tabrecta¹.

'The pivotal data published today not only confirm the positive results we've seen previously with Tabrecta treatment in non-small cell lung cancer, but also underscore the value of early and broad molecular testing of patients' tumors to guide treatment decisions for both first-line and previously treated patients, ' said Jeff Legos, Senior Vice President, Head of Oncology Drug Development, Novartis Oncology. 'We know patients with this particularly aggressive form of lung cancer have a poor prognosis; they are often older and more medically fragile. We are committed to continuing to work with global health authorities to bring Tabrecta to patients as quickly as possible.'

Data in the study published today include the following confirmed ORRs by the Blinded Independent Radiology Committee (BIRC) to Tabrecta in the population with MET exon 14 skipping (n=97):

• 68% ORR (95% CI, 48-84) among treatment-naive patients (n=28)¹
• 41% ORR (95% CI, 29-53) among previously treated patients (n=69)¹

In patients with METex14 who responded to treatment with Tabrecta, the study also demonstrated:

• Median duration of response of 12.6 months (95% CI, 5.6-not estimable) in treatment-naive patients (19 responders) and 9.7 months (95% CI, 5.6-13.0) in previously treated patients (28 responders)¹

Thirteen of 14 patients with METex14 had brain metastases at baseline (3 treatment-naive and 10 previously treated patients) and were considered evaluable by the BIRC¹. In a post-hoc analysis, 7 intracranial responses were observed, including 4 complete responses¹.

The study adds to the scientific consensus that METex14 is an oncogenic driver¹.
The most frequently reported treatment-related adverse events (incidence ≥20%) were peripheral edema (43%), nausea (34%), increased blood creatinine (18%), and vomiting (19%). The majority of the AEs were grades 1 or 2¹.

NSCLC accounts for approximately 85% of the 2 million new lung cancer diagnoses each year worldwide, including about 228,000 in the United States^5-6. Nearly 70% of NSCLC patients have a genomic mutation⁷. METex14, a recognized oncogenic driver, occurs in approximately 3-4% of newly diagnosed advanced NSCLC cases (about 4,000 - 5,000 patients in the US annually)^2,4,8-9.

Tabrecta (capmatinib) is a kinase inhibitor that targets MET. Tabrecta is licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis worldwide exclusive development and commercialization rights to capmatinib and certain back-up compounds in all indications.

Indication
TABRECTA™ (capmatinib) tablets is a prescription medicine used to treat adults with a kind of lung cancer called non-small cell lung cancer (NSCLC) that has spread to other parts of the body or cannot be removed by surgery (metastatic), and whose tumors have an abnormal mesenchymal-epithelial transition (MET) gene.

The effectiveness of TABRECTA in these patients is based on a study that measured 2 types of response to treatment (response rate and duration of response). There is no clinical information available to show if patients treated with TABRECTA live longer or if their symptoms improve. There are ongoing studies to find out how TABRECTA works over a longer period of time.

It is not known if TABRECTA is safe and effective in children.

Important Safety Information
TABRECTA may cause serious side effects, such as lung or breathing problems. TABRECTA may cause inflammation of the lungs during treatment that may lead to death. Patients should be advised to contact their health care provider right away if they develop any new or worsening symptoms, including cough, fever, trouble breathing, or shortness of breath.

TABRECTA may cause abnormal blood test results, which may be a sign of liver problems. Patients should be advised that their health care provider will do blood tests to check their liver before starting and during treatment with TABRECTA. Patients should be advised to contact their health care provider right away if they develop any signs and symptoms of liver problems including the skin or the white part of their eyes turning yellow (jaundice), dark or 'tea-colored' urine, light-colored stools (bowel movements), confusion, loss of appetite for several days or longer, nausea and vomiting, pain, aching, or tenderness on the right side of the stomach area (abdomen), or weakness or swelling in the stomach area.

The skin may be sensitive to the sun (photosensitivity) during treatment with TABRECTA. Patients should be advised to use sunscreen or wear clothes that cover their skin during treatment with TABRECTA to limit direct sunlight exposure.

For women of reproductive potential, TABRECTA can harm their unborn baby. They should use an effective method of birth control during treatment with TABRECTA and for 1 week after the last dose. Men who have partners who can become pregnant should use effective birth control during treatment with TABRECTA and for 1 week after the last dose.

Before taking TABRECTA, patients should tell their health care provider about all their medical conditions, including if they have or have had lung or breathing problems other than lung cancer, have or have had liver problems, or if they are pregnant or plan to become pregnant, as TABRECTA can harm their unborn babies. Females who are able to become pregnant should have a pregnancy test before they start treatment with TABRECTA and should use effective birth control during treatment and for 1 week after the last dose of TABRECTA. Patients should be advised to talk to their health care provider about birth control choices that might be right for them during this time and to tell their health care provider right away if they become pregnant or think they may be pregnant during treatment with TABRECTA. Males who have female partners who can become pregnant should use effective birth control during treatment and for 1 week after their last dose of TABRECTA.

Patients should tell their health care provider about all the medicines they take or start taking, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

The most common side effects of TABRECTA include swollen hands, ankles, or feet (peripheral edema); nausea and/or vomiting; tiredness and/or weakness (fatigue, asthenia); shortness of breath (dyspnea); loss of appetite; changes in bowel movements (diarrhea or constipation); cough; pain in the chest; fever (pyrexia); back pain; and decreased weight.

Please see full Prescribing Information for Tabrecta available at https://www.novartis.us/sites/www.novartis.us/files/tabrecta.pdf

Disclaimer
This media update contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as 'potential,' 'can,' 'will,' 'plan,' 'may,' 'could,' 'would,' 'expect,' 'anticipate,' 'seek,' 'look forward,' 'believe,' 'committed,' 'investigational,' 'pipeline,' 'launch,' or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this media update, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this media update will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political, economic and business conditions, including the effects of and efforts to mitigate pandemic diseases such as COVID-19; safety, quality, data integrity or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this media update as of this date and does not undertake any obligation to update any forward-looking statements contained in this media update as a result of new information, future events or otherwise.

About Novartis
Novartis is reimagining medicine to improve and extend people's lives. As a leading global medicines company, we use innovative science and digital technologies to create transformative treatments in areas of great medical need. In our quest to find new medicines, we consistently rank among the world's top companies investing in research and development. Novartis products reach nearly 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 109,000 people of more than 140 nationalities work at Novartis around the world. Find out more at
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References

1. Juergen Wolf, M.D., et al. Capmatinib in METex14-Mutated or MET-Amplified Advanced NSCLC. New England Journal of Medicine. 2020.
2. Data on file. Novartis Calculation. Kantar Health. CancerMPact: lung (non-small cell) stage IV incidence and newly recurrent. Updated December 15, 2018. my.khapps.com.
3. Tong JH, Yeung SF, Chan AW, et al. MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non-Small Cell Lung Carcinoma with Poor Prognosis. Clinical Cancer Research. 2016;22(12):3048-3056.
4. Sadiq AA, Salgia R. MET as a possible target for non-small-cell lung cancer. Journal of Clinical Oncology. 2013;31:1089-1096.
5. World Health Organization. Cancer Fact Sheet, 2018. Available at: https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed February 18, 2020.
6. American Cancer Society. Key Statistics for Lung Cancer. Available at https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed March 10, 2020.
7. Hirsch FR, Suda K, Wiens J, et al. New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016;388:1012-1024.
8. Smyth EC, et al. Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors. Oncology Targets and Therapy. 2014;7:1001-1014.
9. Salgia R. MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale. Molecular Cancer Therapeutics. 2017;16(4):555-565.

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