Novartis announces Tabrecta® first published overall survival and updated overall response data in patients with METex14 metastatic NSCLC

EAST HANOVER,  N.J., June 4, 2021 /PRNewswire/ -- Novartis today announced the first published mature overall survival (OS) and updated overall response rate (ORR) data following treatment with Tabrecta^® (capmatinib) in adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to MET exon 14 skipping (METex14)^1-3. Data from the ongoing, pivotal, multi-cohort Phase II GEOMETRY mono-1 study will be presented today during the 2021 Annual American Society of Clinical Oncology (ASCO) Virtual Scientific Meeting (Poster Discussion Session, Lung Cancer—Non-Small Cell Metastatic; June 4, 2021, 9:00 AM-10:00 AM CT; abstract 9020).

"This new analysis further supports Tabrecta as a cornerstone targeted treatment for METex14 NSCLC patients and highlights the importance of biomarker testing," said Juergen Wolf, MD, from the Center for Integrated Oncology, University Hospital Cologne, and lead investigator of the GEOMETRY study. "The impressive overall survival outcome and confirmed outstanding response in the first-line setting will help oncologists decide upon a therapeutic option for patients."

The analysis includes new data from the treatment-naïve (1L) expansion cohort 7 and previously-treated (2L+) cohort 6, and mature data from previously-reported cohorts, for a total of 160 patients^1,2.

"The introduction of Tabrecta a year ago dramatically changed the treatment landscape for patients with METex14 NSCLC. Now we have further evidence that Tabrecta, the market-leading treatment specifically for METex14 NSCLC patients⁴, has the potential to help people live longer," said Jeff Legos, Senior Vice President, Head of Oncology Drug Development, Novartis Oncology.

The results presented today provide additional data on the efficacy of Tabrecta in both treatment-naïve and previously-treated patients with METex14 metastatic NSCLC²:

• Overall response rate (ORR) based on the Blinded Independent Review Committee (BIRC) assessment per RECIST v1.1:
• 67.9% (95% CI: 47.6, 84.1) and 65.6% (95% CI: 46.8, 81.4) among treatment-naïve patients (Cohort 5b; n= 28 and Cohort 7; n= 32 patients, respectively)
• 40.6% (95% CI: 28.9, 53.1) and 51.6% (95% CI: 33.1, 69.8) among previously-treated patients (Cohort 4; n= 69 and Cohort 6; n= 31 patients, respectively)
• Median duration of response (DOR) based on BIRC assessment:
• 12.6 months (95% Cl: 5.6–NE) and NE (95% CI: 5.5-NE) among treatment-naïve patients (Cohort 5b; n= 28 and Cohort 7; n= 32 patients, respectively)
• 9.7 months (95% Cl: 5.6–13.0) and 8.4 months (95% Cl: 4.2–NE) among previously-treated patients (Cohort 4; n= 69 and Cohort 6; n= 31 patients, respectively)
• Overall survival (OS):
• 20.8 months (95% CI: 12.42, NE [not estimated]) among treatment-naïve patients (Cohort 5b; n= 28)
• 13.6 months (95% CI: 8.61, 22.24) among previously-treated patients (Cohort 4; n= 69)
• Median OS for expansion Cohorts 6 & 7 are not reached

No new safety signals or unexpected safety findings were observed. Ninety-eight percent of subjects had at least one adverse event (AE) of any grade and 50.9% of subjects had at least one serious adverse event (SAE). Thirteen percent were suspected to be treatment-related. The most common adverse events (>20%, all grades) across all cohorts were peripheral edema, nausea, vomiting, increased blood creatinine, dyspnea, fatigue and decreased appetite. The majority of AEs were grade 3 or 4².

Currently, the five-year survival rate for lung cancer is less than 20%⁵, decreasing further when the disease is diagnosed at later stages⁶. Nearly one in three patients with metastatic NSCLC may have an actionable mutation^7,8. METex14 has been reported to occur in 3%-4% of metastatic NSCLC cases⁹. Many patients with mutations that lead to METex14 are not diagnosed with NSCLC until their disease has progressed to later stages and often have poor prognosis^10,11.

A separate analysis of patient-reported outcomes (PROs) evaluated cough, delayed time to lung symptom deterioration, and quality of life (QoL) in NSCLC patients with METex14 (abstract 9056)³.

• Median time to definitive deterioration (TTDD) in global health status (GHS) was 16.6 months (95% CI: 9.7, NE) and 12.4 months (95% CI: 4.2, 19.4) in 1L and 2L+ patients, respectively
• Median TTDD for cough and chest pain was NE in both 1L and 2L+ patients, and for dyspnea was 19.4 months (95% CI: 12.4, NE) and 22.1 months (95% CI: 9.9, NE), respectively
• An exploratory post hoc analysis evaluated QLQ-LC13 symptoms (cough, chest pain, and dyspnea) over time for patients achieving a clinical response, as assessed by BIRC, found these symptoms improved at all cycles in patients achieving clinical complete response (CR) or partial response, while symptom worsening was seen in those with no clinical response

Additionally, a retrospective analysis of GEOMETRY mono-1 validates the clinical utility of liquid biopsy testing to identify METex14 positive patients for treatment with Tabrecta (Poster Session: Lung Cancer—Non-Small Cell Metastatic; abstract 9111)¹².

Visit https://www.hcp.novartis.com/virtual-congress/a-2021/ for the latest information from Novartis, including our commitment to the Oncology community, and access to our ASCO21 Virtual Scientific Program data presentations (for registered participants).

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

Patients were assigned to cohorts on the basis of MET status and previous lines of therapy¹³. 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 BIRC.

About Tabrecta (capmatinib)
Tabrecta (capmatinib) 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. In May 2020, Tabrecta was approved by the US Food and Drug Administration (FDA) for adult patients with metastatic NSCLC whose tumors have a mutation that leads to METex14 as detected by an FDA-approved test. This indication was approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

In June 2020, Tabrecta was approved by the Japanese Ministry of Health, Labour and Welfare (MHLW) for adult patients with metastatic NSCLC whose tumors have a mutation that leads to METex14 as detected by an FDA-approved test.  Tabrecta was also approved in Hong Kong in February 2021 and Switzerland in April 2021.

Novartis and Lung Cancer
Lung cancer is the most common cancer worldwide, accounting for more than 2 million new cases diagnosed each year¹⁴. There are two main types of lung cancer – small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC)^15,16. NSCLC accounts for approximately 85% of lung cancer diagnoses, resulting in nearly 2 million new cases each year^14,16. More people die of lung cancer every year than any other cancer type¹⁴. Treatment options are limited for people with lung cancer who experience cancer growth or progression while on current standard of care treatments^17-19.

Novartis is committed to developing best-in-class treatments for lung cancer patients around the world. With a focus on both targeted, personalized medicine and the role of newer core immuno-oncology therapies, the lung cancer drug development program at Novartis is among the most robust in the industry. Novartis research activities are informed by our long-term relationships with leading lung cancer thought leaders and patient advocates. With them, Novartis is committed to reimagining the treatment of lung cancer.

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 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
Located in East Hanover, NJ Novartis Pharmaceuticals Corporation – an affiliate of 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 employs nearly 16,000 people in the United States. For more information, please visit https://www.novartis.us.

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References

1.  ClinicalTrials.gov. A Study of Capmatinib (INC280) in NSCLC Patients With MET Exon 14 Alterations Who Have Received Prior MET Inhibitor. (2016). Available at: https://clinicaltrials.gov/ct2/show/NCT02750215. Accessed March 2021.

2.  Wolf, J. et.al. Capmatinib in MET exon 14-mutated, advanced NSCLC: updated results from the GEOMETRY mono-1 study. Abstract #9020. 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, Chicago, IL.

3.  Wolf, J. et.al. Patient-reported outcomes in capmatinib-treated patients with METex14- mutated advanced NSCLC: Results from the phase II GEOMETRY mono-1 study. Abstract #9056. 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, Chicago, IL.

4.  IQVIA. Weekly / Daily Module Views- Rx Weekly (NPA). Accessed April 5, 2021.

5.  Siegel R, Miller K, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30.

6.  Rami-Porta R, Asamura H, Traves W, et al. Lung cancer – major changes in the American Joint Committee on Cancer eight edition cancer staging manual. CA Cancer J Clin. 2017;67:138.

7.  Tsang ES, et al. Clinical outcomes after whole-genome sequencing in patients with metastatic non-small cell lung cancer. Cold Spring Harb Mol Case Stud. 2019.5:a002659.

8.  Shea M, et. al. Management of advanced non-small cell lung cancers with known mutations or rearrangements: latest evidence and treatment approaches. Therapeutic Advances in Respiratory Disease. 2016;10(2) 113–129.

9.  Salgia R. MET in lung cancer: biomarker selection based on scientific rationale. Molecular Cancer Therapeutics. 2017;16(4):555-565.

10.  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.

11.  Tong JH, Yeung SF, Chan Al. MET amplification and exon 14 splice site mutation define unique molecular subgroups of on-small cell lung carcinoma with poor prognosis. Clin Cancer Res. 2016;22:3048-3056.

12.  Heist, RS, et.al. Capmatinib efficacy in patients with NSCLC identified as METex14 using an NGS based liquid biopsy assay: results from the GEOMETRY mono-1 study. Abstract #9111. 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, June 4-8, Chicago, IL.

13.  Juergen Wolf, M.D., et al. Capmatinib in METex14-Mutated or MET-Amplified Advanced NSCLC. New England Journal of Medicine. 2020.

14.  World Health Organization. Cancer. Available at: https://www.who.int/news-room/fact-sheets/detail/cancer. Accessed on February 9, 2021.

15.  Lemjabbar-Alaoui H, Hassan O, Yang UW, et al. Lung cancer: biology and treatment options. Biochim Biophys Acta. 2015. 1856(2):189-210.

16.  American Cancer Society. About Lung Cancer. Available at https://www.cancer.org/cancer/non-small-cell-lung-cancer/about/what-is-non-small-cell-lung-cancer.html. Accessed February 9, 2021.

17.  National Comprehensive Cancer Network Guidelines. Non-small cell lung cancer. Version 4. 2021.

18.  Sandler A, Gray R, Perry M, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. New Engl J Med. 2006; 355: 2452-2550.

19.  Gadgeel S, Rodriguez-Abreu D, Speranza G, et al. Updated analysis from KEYNOTE-189: pembrolizumab or placebo plus pemetrexed and platinum for previously untreated metastatic nonsquamous non-small cell lung cancer. J Clin Oncol. 2020; 38:1505-1517.

*FoundationOne^®CDx is a registered trademark of Foundation Medicine, Inc.

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