Novartis receives positive CHMP opinion for Tabrecta® for patients with METex14 advanced non-small cell lung cancer

• Opinion based on Phase II GEOMETRY mono-1 study showing an overall response rate (ORR) of 51.6% in a cohort evaluating second-line patients only and 44% in all previously-treated patients with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to MET exon 14 (METex14) skipping¹
• Tabrecta^® (capmatinib) is the number one prescribed targeted therapy for advanced NSCLC with alterations leading to METex14 skipping globally²
• METex14 skipping is a recognized oncogenic driver occurring in 3-4% of NSCLC cases; therapies targeting difficult-to-treat mutations may provide new options for patients^3,4
• With one of the most diverse lung cancer development programs, Novartis is focused on investments to advance the science, drive treatment and make an impact for patients

Basel, April 22, 2022 — Novartis announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion and recommended granting marketing authorization of Tabrecta^® (capmatinib) as a monotherapy for the treatment of adults with advanced non-small cell lung cancer (NSCLC) harboring alterations leading to mesenchymal-epithelial-transition factor gene (MET) exon 14 (METex14) skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.

“Patients with alterations leading to METex14 skipping have an urgent need for treatment options, as this form of lung cancer is aggressive, often diagnosed in an advanced stage and frequently comes with a poor prognosis,” said Juergen Wolf, MD, from the Center for Integrated Oncology, University Hospital Cologne, Germany, and lead investigator of the GEOMETRY mono-1 trial. “The positive CHMP opinion for Tabrecta brings an option to patients for a treatment specific to their tumor. If approved by the European Commission, new targeted therapies like Tabrecta—supported by early and broad molecular testing of patients’ tumors—can better guide treatment decisions and ensure patients receive the appropriate therapy for their cancer.”

The CHMP opinion is based on results from the Phase II GEOMETRY mono-1 trial that demonstrated positive overall response rates (ORR) among adult patients with advanced NSCLC whose tumors had alterations leading to METex14 skipping¹. Based on data presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, among 31 patients who received Tabrecta as second-line therapy in the METex14 skipping pretreated population, a confirmed ORR of 51.6% (95% CI, 33.1-69.8) was achieved, and the ORR across all 100 previously-treated patients, which included patients who received one or two prior lines of systemic therapy, was 44.0% (95% CI, 34.1-54.3)¹. The most common treatment-related adverse events (AEs) (incidence ≥20%)were peripheral oedema, nausea, fatigue, vomiting, dyspnea, decreased appetite and back pain¹.

“Every 30 seconds, someone dies of lung cancer—the need for more treatment options is critical. Through research and targeted therapies like Tabrecta, we are working to change that statistic and make a positive impact on the lives of people affected by cancer around the world,” said Marie-France Tschudin, President, Innovative Medicines International & Chief Commercial Officer, Novartis. “Today’s announcement represents an important step forward for people in the European Union with previously-treated advanced NSCLC having alterations leading to METex14 skipping.”

In the European Union, there are an estimated 291,000 patients with locally advanced or metastatic NSCLC⁵. METex14 skipping, a recognized oncogenic driver, occurs in approximately 3-4% of NSCLC cases^3,4.

About Tabrecta (capmatinib)
Tabrecta (capmatinib) is approved in several countries including the US, Switzerland and Japan. It is the number one prescribed targeted therapy for patients with advanced NSCLC with alterations leading to METex14 skipping globally².

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

About GEOMETRY mono-1 
GEOMETRY mono-1 is a Phase II multi-center, non-randomized, open-label, multi-cohort study in adult patients with EGFR wild-type, ALK-negative rearrangement, advanced NSCLC with alterations that lead to MET exon-14 skipping who received 400 mg of capmatinib orally twice daily¹.

Patients were assigned to cohorts on the basis of MET status and previous lines of therapy. The primary endpoint was overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1. The key secondary endpoint was duration of response (DOR) evaluated by BIRC¹.

Mature data from the trial, including from an expansion cohort analysis, showed Tabrecta demonstrated a median duration of response of 9.7 months (95% CI, 5.6-13.0) in all previously-treated patients (n=100)¹. In addition, Tabrecta demonstrated a median overall survival of 13.6 months (95% CI, 8.6-22.2) in previously-treated patients (n=69)¹. The median progression-free survival was 5.5 months (95% CI, 4.2‑8.1) for all previously-treated patients (n=100) and 6.9 months (95% CI, 4.2-13.3) for patients who received Tabrecta as second-line therapy (n=31)¹. The Disease Control Rate across all previously-treated patients was 82.0% (95% CI, 73.1-89.0)¹. The expansion cohort analysis enrolled 160 patients with MET alterations and included previously-treated cohorts (n=100) who had been treated with one or two prior lines of systemic therapy for advanced disease, as well as treatment-naive cohorts (n=60)¹.

Overall, Tabrecta demonstrated a manageable safety profile and there were no new safety signals or unexpected safety findings¹. The most common treatment-related adverse events (AEs) (incidence ≥20%) were peripheral oedema, nausea, fatigue, vomiting, dyspnea, decreased appetite and back pain¹.

About MET exon 14 skipping
MET (mesenchymal-epithelial transition), a receptor tyrosine kinase coded by the MET gene, normally plays an important role in cell signaling, proliferation and survival³. Many cancers are associated with abnormal signaling through the MET receptor pathway, caused by multiple mechanisms including point mutations, insertions and deletions that lead to skipping of exon 14. MET exon 14 (METex14) skipping is an oncogenic alteration in NSCLC that can result in overstimulation of the MET pathway³.

Patients with alterations that lead to METex14 skipping often have a poor prognosis due to the aggressiveness of the cancer and limited treatment options^6-8.

Novartis and lung cancer
The needs in lung cancer are urgent and significant. Each year, more than 2 million people are newly diagnosed globally, and lung cancer remains the number one cause of cancer-related death worldwide⁹. There are two main types of lung cancer—small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC accounts for approximately 85% of lung cancer diagnoses¹⁰.

Novartis is making bold investments in advancing the science to drive treatment and make an impact for patients around the world. The company is committed to working with the scientific and medical communities to reimagine the treatment of lung cancer and pursue advances in medicine that could extend the survival of people living with lung cancer. 

With one of the most diverse lung cancer development programs in the industry, Novartis is developing therapies that block cancer growth; learning more about ways to activate the body’s immune system; increasing understanding of the relationship between unregulated inflammation and tumor growth and recurrence; and exploring the potential for advanced nuclear medicine to fight the disease. Through these programs, Novartis aims to redefine possibilities in lung cancer and pursue a trajectory to make lung cancer history.

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,” “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 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 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 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 800 million people globally and we are finding innovative ways to expand access to our latest treatments. About 108,000 people of more than 140 nationalities work at Novartis around the world. Find out more at https://www.novartis.com.

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References

1. Wolf J, Garon EB, Groen HJM, Tan DSW, Robeva A, Le Mouhaer S, et al. Capmatinib in MET exon 14-mutated, advanced NSCLC: updated results from the GEOMETRY mono-1 study. Poster presented at 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, Chicago, IL.
2. Novartis data on file.
3. Sadiq AA, Salgia R. MET as a possible target for non-small-cell lung cancer. J Clin Oncol. 2013;31:1089.
4. Salgia R. MET in lung cancer: biomarker selection based on scientific rationale. Mol Cancer Ther. 2017;16(4):555-565.
5. Novartis data on file.
6. 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. 2016;22:3048-3056.
7. Cappuzzo F, Marchetti A, Rossi E. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol. 2009;27:1667-1674.
8. Smyth EC, et al. Emerging molecular targets in oncology: clinical potential of MET/hepatocyte growth-factor inhibitors. Onco Targets Ther. 2014;7:1001-1014.
9. World Health Organization. Cancer. Available at: https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed March 21, 2022.
10. American Cancer Society. What is lung cancer? Available at: https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed March 21, 2022.

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