Novartis phase II GEOMETRY mono-1 trial of investigational medicine capmatinib (INC280) shows positive results in patients with MET mutated advanced NSCLC

• Phase II study efficacy data showed overall response rate of 72.0% and 39.1%, respectively, in treatment-naive and previously treated patients with advanced MET exon-14 skipping mutated non-small cell lung cancer (NSCLC)
   
• Clinical findings from ongoing study indicate safety profile was consistent with previously reported data results 
   
• Capmatinib, an investigational MET inhibitor, may have the potential to improve response rates for people diagnosed with MET exon-14 skipping mutated NSCLC, a known oncogenic driver

Basel, October 19, 2018 - Novartis today announced Phase II preliminary results of the GEOMETRY mono-1 clinical trial of investigational MET inhibitor capmatinib (INC280) in 94 adult patients with advanced non-small cell lung cancer (NSCLC) harboring MET exon-14 skipping mutations. The GEOMETRY mono-1 study showed an overall response rate (ORR) of 72.0% (95% CI: 50.6-87.9) in treatment-naive patients and 39.1% (95% CI: 27.6-51.6) in previously treated patients. ORR was assessed by blinded independent review committee (BIRC). Adverse events (AEs) were consistent with previously reported data and no new safety signals were observed. Results of the Phase II study were presented today at the European Society for Medical Oncology (ESMO) 2018 Congress [October 19, 2018 at 4:45 PM CET] (Abstract #LBA52)[1].

"These preliminary findings reveal the potential of capmatinib in MET exon-14 skipping mutated NSCLC patients. Compared to the previously treated patient groups, the primary advantage in terms of overall response rate reported in treatment-naive patients highlights the clinical relevance for an earlier diagnostic testing and prompt treatment of this challenging patient population," said Juergen Wolf, MD, University Hospital Cologne.

NSCLC is the most common type of lung cancer, impacting more than 2 million people per year[2]. Approximately 3-4% of all patients with NSCLC have an identified MET mutation[3]. Though rare, this mutation is an indicator of especially poor prognosis and there is currently no approved therapy designed to target this mutation[4].

"Patients diagnosed with advanced MET mutated NSCLC represent an unmet medical need and often face a poor prognosis," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "We are encouraged by the GEOMETRY mono-1 results and the potential for capmatinib to help patients with this disease."

About GEOMETRY mono-1
The GEOMETRY mono-1 trial is a multicenter, open-label, phase II study to evaluate the efficacy and safety of single-agent INC280 in adult patients with EGFR wildtype, ALK-negative rearrangement, advanced NSCLC harboring MET amplification and/or mutations. Patients with MET exon-14 skipping were assigned to Cohorts 4 (previously treated patients) or 5B (treatment naive) regardless of MET amplification/gene copy number (centrally confirmed), and received 400 mg capmatinib tablets twice daily. The primary endpoint was ORR based on BIRC assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) by BIRC. The GEOMETRY mono-1 study found an ORR in the treatment-naive patients (n=25) of 72.0% (95% CI: 50.6-87.9) and an ORR in the previously treated patients (n=69) of 39.1% (95% CI: 27.6-51.6). DOR was not reached by the time of analysis, indicating sustainability of response[1],[6]. 

The most common treatment-related AEs included peripheral edema, nausea, vomiting, and increased blood creatinine levels. Of patients treated with INC280, 83.8% experienced an AE, with 33.1% having grade 3/4 AEs[1],[6].

Capmatinib (INC280) is an investigational, oral and selective MET inhibitor licensed to Novartis by Incyte Corporation in 2009. Under the Agreement, Incyte granted Novartis exclusive Development and Commercialization worldwide rights to this MET inhibitor compound and certain back-up compounds in all indications.

Novartis Commitment to Lung Cancer
Worldwide, lung cancer causes more deaths than colon, breast and prostate cancer combined, and over 2 million new cases of lung cancer are diagnosed each year[2]. Among patients with NSCLC, almost 70% have an actionable mutation that may be targeted with available therapies[7]. To determine the most appropriate treatment, medical organizations recommend genomic testing for patients with lung cancer[8].

Novartis Oncology's research in NSCLC has helped transform treatment approaches for patients living with mutation-driven diseases, among others. Novartis continues its commitment to the global lung cancer community through ongoing studies, as well as the exploration of investigational compounds that target genetic biomarkers in NSCLC.

Disclaimer
This press release 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," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by expressed or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, 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 press release 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; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality 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 press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release 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 1 billion people globally and we are finding innovative ways to expand access to our latest treatments. About 125,000 people of more than 140 nationalities work at Novartis around the world. Find out more at www.novartis.com.

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References
            [1]   Juergen Wolf. Results of the GEOMETRY mono-1 phase II study for evaluation of the MET inhibitor capmatinib (INC280) in patients with MET exon-14 skipping mutated advanced non-small cell lung cancer. Abstract #LBA52. 2018 European Society of Medical Oncology (ESMO), October 19-23, 2018, Munich, Germany.
            [2]   Globocan. Lung Fact Sheet. Available at http://gco.iarc.fr/today/data/factsheets/cancers/15-Lung-fact-sheet.pdf. Accessed October 9, 2018.
            [3]   Salgia R. MET in Lung Cancer: Biomarker Selection Based on Scientific Rationale. Mol Cancer Ther. 2017;16(4):555-565.
            [4]   Tong JH, Yeung SF, Chan AWH, 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. 2016;22(12):3048-3056.
            [5]   Lungevity. Targeted Therapy: What is driver mutation? Available at https://lungevity.org/for-patients-caregivers/lung-cancer-101/treatment-options/targeted-therapy. Accessed October 9, 2018.
            [6]   A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor. (2016). Retrieved from http://clinicaltrials.gov/ct2 (Identification No. NCT02750215).
            [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]   Lindeman NI, Cagle PT, Beasley MB, et al. Molecular Testing Guideline for Selection of Lung Cancer Patients for EGFR and ALK Tyrosine Kinase Inhibitors. J Thorac Oncol. 2013;8(7):823-859.

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