Novartis today announced that The New England Journal of Medicine (NEJM) published clinical trial results showing the investigational compound LDK378 (ceritinib) achieved an overall response rate (ORR, including complete response [CR] and partial response [PR]) of 58% and a median progression-free survival (PFS) of seven months in adults with advanced anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) who received 400 mg or higher of LDK378 per day.
The study evaluated 114 ALK+ NSCLC patients treated with LDK378, including patients who had progressed during or following treatment with a commonly prescribed ALK inhibitor called crizotinib and those who had not received prior treatment with an ALK inhibitor1. This study is part of the ongoing Novartis clinical trial program in this patient population.
"The majority of patients in the study experienced a clinical response to LDK378. In addition, responses were seen in untreated lesions in the central nervous system in patients who previously received crizotinib," said lead investigator Alice T. Shaw, MD, PhD, Massachusetts General Hospital Cancer Center, Boston. "These results are important because most patients experience a disease relapse less than a year after starting crizotinib and have limited treatment options."
Non-small cell lung cancer is the most common type of lung cancer, accounting for 85-90% of all cases, with 2-7% of those patients having the ALK gene rearrangement that increases the growth of cancer cells. Currently, there are limited treatment options for patients with ALK+ NSCLC, who tend to be non-smokers and younger than NSCLC patients who are not ALK+.
The study results published in NEJM demonstrated a median PFS of 7.0 months [95% CI; 5.6-9.5 months] in patients with ALK+ NSCLC treated with LDK378 at doses of 400 mg to the maximum tolerated dose of 750 mg per day. The study also reported an ORR of 59% [95% CI; 47-70%] in patients taking LDK378 at 750 mg per day1. The responses observed demonstrated LDK378 is active in patients with advanced ALK+ NSCLC, including those who were previously treated with crizotinib, with or without new mutations in the ALK gene.
The most frequent adverse events were nausea (82%), diarrhea (75%), vomiting (65%), fatigue (47%) and increased alanine aminotransferase levels (35%)1. Preliminary data from this publication were first presented at the 2013 American Society of Clinical Oncology annual meeting4. The study is ongoing with more data to become available.
"These pivotal data published in NEJM served as the basis for our first regulatory filing for LDK378," said Alessandro Riva, President, Novartis Oncology ad interim and Global Head, Oncology Development and Medical Affairs. "We are pleased that the FDA has accepted our application, and we look forward to working with the FDA and health authorities worldwide to bring this important treatment option to patients in need as swiftly as possible."
The FDA designated LDK378 as a Breakthrough Therapy, which is intended to expedite the development and review of drugs that treat serious or life-threatening conditions if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint.
Several major studies evaluating treatment with LDK378 are being conducted in more than 300 study centers across more than 30 countries. Currently, two Phase II clinical trials (www.clinicaltrials.gov identifiers NCT01685060 and NCT01685138) are fully enrolled and ongoing. In addition, two Phase III clinical trials (www.clinicaltrials.gov identifiers NCT01828099 and NCT01828112) are ongoing and are actively recruiting patients worldwide to further evaluate LDK378 in patients with ALK+ NSCLC.
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