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Study shows Zykadia™ shrank tumors in the majority of patients with ALK+ NSCLC, regardless of prior ALK treatment

Novartis has announced data showing Zykadia™ (ceritinib, previously known as LDK378) shrank tumors in patients with anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC), including those who had received previous treatment with an ALK inhibitor as well as patients receiving one for the first time. Results were also observed in patients with ALK+ NSCLC who entered the study with brain metastases1.

The study is being presented at the 50th Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

“Ceritinib demonstrated a high level of activity in patients with ALK+ NSCLC regardless of whether or not they were previously treated with an ALK inhibitor,” said lead investigator Dong-Wan Kim, MD, PhD, Seoul National University Hospital. “Another noteworthy finding in this study population is that ceritinib exhibited activity among patients whose cancer had metastasized to the brain, which is currently one of the biggest challenges in treating ALK+ NSCLC.”

Among a combined population of 246 NSCLC patients, ceritinib achieved an overall response rate (ORR) of 58.5% and a median progression-free survival (PFS) of 8.2 months. Of these, 124 patients entered the trial with brain metastases and achieved an ORR of 54.0% and a median PFS of 6.9 months. The most common adverse events, occurring in more than half of patients, were diarrhea, nausea, vomiting, abdominal pain and fatigue1.

Approximately 2-7% of patients with NSCLC harbor the ALK gene rearrangement, which causes cancer growth3. These patients are candidates for treatment with a targeted ALK inhibitor. Patients with ALK+ NSCLC are often younger than the average NSCLC patient, and in many cases have never smoked4.

“We are encouraged that ceritinib has demonstrated consistent activity as we analyze data from additional patients with longer follow-up, further supporting the potential of ceritinib to make a difference in the lives of patients with ALK+ NSCLC,” said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. “The recent FDA approval of Zykadia brought an important new treatment option to patients in the US and we are pleased to be working with regulatory authorities around the world to bring ceritinib to additional patients.”

The study presented at ASCO served as the basis for the US Food and Drug Administration (FDA) approval of Zykadia in April 2014, which followed the FDA’s Breakthrough Therapy designation, and occurred less than three and a half years after the first patient entered a clinical trial. Additional ongoing regulatory reviews are currently underway in the European Union, Argentina and Switzerland.

About the study and ceritinib clinical trial program

The 246 patients with ALK+ NSCLC in this Phase I single-arm study received ceritinib 750 mg daily and had a 7-month median duration of follow-up. Of these, 166 (67%) had received at least two prior regimens and 163 (66%) had been previously treated with an ALK inhibitor. Findings from the study showed that patients treated with ceritinib achieved an ORR of 58.5% [95% CI, 52.1-64.8%] and a median PFS of 8.2 months [95% CI, 6.7-10.1 months]. The median duration of response was 9.7 months [95% CI, 7.0-11.4 months], with a median time to first response of 6 weeks after starting treatment1.

Among 163 patients receiving 750 mg of ceritinib daily and who were previously treated with the commonly prescribed ALK inhibitor crizotinib, ORR was 54.6% [95% CI, 46.6-62.4%] and PFS was 6.9 months [95% CI, 5.4-8.4 months]. In 83 patients who had not received prior treatment with an ALK inhibitor, ORR was 66.3% [95% CI, 55.1-76.3%] and PFS had not been reached (NR) at the time of data cutoff as the majority of patients were still receiving treatment with ceritinib1.

In the 124 patients who started the study with brain metastases, ceritinib achieved an ORR of 54.0% [95% CI, 44.9-63.0%] and a median PFS of 6.9 months [95% CI, 5.4-8.4 months]. Tumor shrinkage was seen in 50.0% of patients [49 of 98 patients; 95% CI, 39.7-60.3%] with brain metastases who had received previous ALK inhibitor therapy, while 69.2% of patients [18 of 26 patients; 95% CI, 48.2-85.7%] with brain metastases who were not previously treated with an ALK inhibitor achieved tumor shrinkage following treatment with ceritinib1.

Discontinuation of treatment due to adverse events occurred in 10% of patients1.

Among 255 patients treated with ceritinib, including 246 patients with NSCLC and nine patients with other types of cancer, 150 (59%) required at least one dose reduction. The most frequent adverse events (incidence >50%) among 255 patients were diarrhea (86%), nausea (80%), vomiting (60%), abdominal pain (54%) and fatigue (52%). The most common lab abnormalities (incidence >50%) were decreased hemoglobin (84%), increased ALT (80%), AST increased (75%) and increased creatinine (58%). The most common Grade 3/4 lab abnormalities (incidence >10%) were increased ALT (27%), increased AST (13%) and increased glucose (13%)1.

This study is part of the ongoing Novartis clinical trial program in this patient population. Several major studies evaluating treatment with ceritinib are being conducted in more than 300 study centers across more than 30 countries. Two Phase II single-arm clinical trials in previously treated and treatment-naïve ALK+ NSCLC patients, (www.clinicaltrials.gov identifiers NCT01685060 and NCT01685138), are fully enrolled and ongoing. In addition, two Phase III clinical trials comparing ceritinib with chemotherapy in treatment-naïve and in previously-treated patients, (www.clinicaltrials.gov identifiers NCT01828099 and NCT01828112), are ongoing and actively recruiting patients worldwide5,6,7,8.

About Zykadia

Zykadia (ceritinib) is indicated in the US for the treatment of patients with ALK+ metastatic NSCLC who have progressed on or are intolerant to crizotinib. This indication is approved under accelerated approval based on tumor response rate and duration of response. An improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Zykadia is an FDA-approved prescription medicine that is currently available through a number of specialty pharmacies in the US. Outside of the US, Zykadia (LDK378) is an investigational agent and has not been approved by regulatory authorities.


1. Kim, DW. Ceritinib in Advanced Anaplastic Lymphoma Kinase (ALK)-rearranged (ALK+) Non-small Cell Lung Cancer (NSCLC) – Results of the ASCEND-1 Trial. Abstract #8003. 2014 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, USA.

2. Zykadia™ (ceritinib) Prescribing Information. East Hanover, New Jersey, USA: Novartis Pharmaceuticals Corporation; April 2014.

3. National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Non-Small Cell Lung Cancer. NCCN 2014 3:1-148.

4. Shaw A, et al. Targeting Anaplastic Lymphoma Kinase in Lung Cancer. Clin Cancer Res 2011;17:2081-2086.

5. ClinicalTrials.gov. LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib. Available at: http://clinicaltrials.gov/ct2/show/NCT01685060?term=%22LDK378%22+and+%22Phase+II%22&rank=1. Accessed on May 12, 2013.

6. ClinicalTrials.gov. LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-Small Cell Lung Cancer. Available at: http://clinicaltrials.gov/ct2/show/NCT01685138?term=%22LDK378%22+and+%22Phase+II%22&rank=2. Accessed on May 12, 2013.

7. ClinicalTrials.gov. LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-Small Cell Lung Cancer. Available at: http://clinicaltrials.gov/ct2/show/NCT01828099?term=%22LDK378%22+and+%22Phase+III%22&rank=1 Accessed on May 12, 2013.

8. ClinicalTrials.gov. LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib. Available at: http://clinicaltrials.gov/ct2/show/NCT01828112?term=%22LDK378%22+and+%22Phase+III%22&rank=2 Accessed on May 12, 2013.

Novartis Pharmaceuticals Corporation