Novartis Breakthrough Therapy LDK378 shows a marked clinical response in patients with ALK+ non-small cell lung cancer

EAST HANOVER, N.J., June 3, 2013 /PRNewswire/ -- Novartis today announced data on its investigational compound LDK378 showing a marked clinical response in 78 patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC) who had progressed during or after crizotinib therapy or had not been previously treated with crizotinib¹. The trial will be featured as an oral presentation (abstract #8010; Monday, June 3) at the 49^th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

The results from the study showed an overall response rate (including complete response [CR] and partial response [PR]) of 60% in patients with ALK+ NSCLC taking LDK378 (750 mg/day), which includes patients who had progressed during or after crizotinib therapy (overall response rate of 59%) and those who were crizotinib-naive (overall response rate of 62%)¹. In addition to the 78 patients treated at 750 mg/day, an additional 36 patients were treated with LDK378 at 400-750 mg/day. The study is continuing to enroll patients and evaluations are ongoing. This pivotal trial will serve as the basis for the first regulatory filing, anticipated in early 2014.

The most frequent adverse events (regardless of relationship to LDK378) were nausea (73%), diarrhea (72%), vomiting (58%) and fatigue (41%). The most frequent Grade 3/4 adverse events were alanine aminotransferase increased (19%), aspartate aminotransferase increased (10%) and diarrhea (8%).

"These results confirm that LDK378 has activity in patients with ALK+ NSCLC, including those who have progressed on crizotinib, as well as those who haven't taken crizotinib," said lead investigator Alice T. Shaw, MD, PhD, Massachusetts General Hospital Cancer Center, Boston. "LDK378 may become another standard targeted therapy for these ALK-positive patients."

In March, LDK378 received Breakthrough Therapy designation from the US Food and Drug Administration (FDA). The designation is intended to expedite the development and review of drugs that treat life-threatening conditions and show improvement over available therapies².

"LDK378 is representative of the Novartis targeted research approach to identify key disease pathways and those specific patients affected by the disease," said Herve Hoppenot, President, Novartis Oncology. "Based on these data showing the potential of LDK378, we are developing a robust clinical program to move it forward as quickly as possible."

Currently, two Phase II clinical trials are actively recruiting patients worldwide. One study, highlighted as a Trials in Progress poster at ASCO, focuses on patients with ALK+ NSCLC who were previously treated with chemotherapy and crizotinib (presented on Saturday, June 1 from 8:00 – 11:45 AM; abstract #TPS8119). The second study examines LDK378 in patients who are crizotinib-naive. In addition, Phase III clinical trials are planned to begin in the coming months, aiming to enroll more than 1,100 patients with ALK+ NSCLC at sites worldwide.

Non-small cell lung cancer is the most common type of lung cancer accounting for 85-90% of all cases³. Approximately 3-8% of patients with NSCLC have the ALK gene mutation¹. There are limited treatment options for patients with ALK+ NSCLC, who tend to be non-smokers and younger than NSCLC patients without an ALK translocation⁴.

About the study
The Phase I single-arm study investigated the maximum tolerated dose, safety, pharmacokinetics and preliminary antitumor activity of LDK378 in 114 patients with ALK+ NSCLC (78 patients taking LDK378 at 750 mg/day and 36 additional patients taking 400-750 mg/day). Of 114 patients evaluable for response, 79 had progressed during or following treatment with crizotinib, and 35 patients with NSCLC were crizotinib-naive¹.

In the 78 patients with ALK+ NSCLC who received LDK378 at 750 mg/day, the overall response rate was 60% (47 patients had partial responses). In the 114 patients treated with LDK378 at 400 mg/day or higher, the overall response rate was 58% (1 patient had a complete response and 65 patients had partial responses).

The median duration of response for patients treated at 400 mg/day or higher (n=66) was 8.2 months (95% confidence interval [CI], 6.9-NE), with a median progression-free survival of 8.6 months (95% CI; 5.7-9.9). The six month duration of response rate at 750 mg/day was 61% (95% CI; 34.9-78.8).

About LDK378 
LDK378 is a selective inhibitor of a cancer target called anaplastic lymphoma kinase or ALK. Because it is an investigational compound, the safety and efficacy profile of LDK378 has not yet been established. Access to this investigational compound is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of this compound. Because of the uncertainty of clinical trials, there is no guarantee that LDK378 will ever be commercially available anywhere in the world.

Disclaimer
The foregoing release contains forward-looking statements that can be identified by terminology such as "will," "Breakthrough Therapy," "anticipated," "may," "potential," "planned," "aiming," or similar expressions, or by express or implied discussions regarding potential marketing approvals for LDK378 or regarding potential future revenues from LDK378. You should not place undue reliance on these statements. Such forward-looking statements reflect the current views of management regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with LDK378 to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that LDK378 will be submitted or approved for sale in any market or at any particular time. Nor can there be any guarantee that LDK378 will achieve any particular levels of revenue in the future. In particular, management's expectations regarding LDK378 could be affected by, among other things, negative or otherwise unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; government, industry and general public pricing pressures; competition in general; unexpected manufacturing issues; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; the impact that the foregoing factors could have on the values attributed to the Novartis Group's assets and liabilities as recorded in the Group's consolidated balance sheet, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. 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, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG, which provides innovative healthcare solutions that address the evolving needs of patients and societies. Headquartered in Basel, Switzerland, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, eye care, cost-saving generic pharmaceuticals, preventive vaccines and diagnostic tools, over-the-counter and animal health products. Novartis is the only global company with leading positions in these areas. In 2012, the Group achieved net sales of USD 56.7 billion, while R&D throughout the Group amounted to approximately USD 9.3 billion (USD 9.1 billion excluding impairment and amortization charges). Novartis Group companies employ approximately 129,000 full-time-equivalent associates and operate in more than 140 countries around the world. For more information, please visit http://www.novartis.com.

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References

1. Shaw A, et al. Clinical activity of the ALK inhibitor LDK378 in advanced, ALK-positive NSCLC. Abstract #8010.49th American Society of Clinical Oncology (ASCO) Chicago, IL.
2. US Food and Drug Administration. Frequently Asked Questions: Breakthrough Therapies. Available at: http://www.fda.gov/RegulatoryInformation/Legislation/FederalFoodDrugandCosmeticActFDCAct/SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Accessed May 30, 2013.
3. American Cancer Society. Lung Cancer – Non-Small Cell Detailed Guide. Available at: http://www.cancer.org/Cancer/LungCancer-Non-SmallCell/DetailedGuide/non-small-cell-lung-cancer-what-is-non-small-cell-lung-cancer. Accessed May 30, 2013.
4. Shaw A, et al. Targeting Anaplastic Lymphoma Kinase in Lung Cancer. Clin Cancer Res 2011;17:2081-2086.

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