LDK378 in Adult Patients With ALK-activated NSCLC Previously Treated With Chemotherapy and Crizotinib

A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Adult Patients With ALK-activated Non-small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib

A single-arm, open-label, multicenter, phase II study. Treatment with LDK378 750 mg qd continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anti-cancer therapy and/or died. LDK378 could be continued beyond RECIST-defined progressive disease (PD) as assessed by the investigator if, in the judgment of the investigator, there was evidence of clinical benefit. In these patients tumor assessment would continue as per the schedule of assessments until treatment with LDK378 was permanently discontinued. Patients who discontinued the study medication in the absence of progression continued to be followed for tumor assessment until the time of PD as assessed by the investigator

Inclusion critieria:

• Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carries an ALK rearrangement, as per the FDA-approved FISH assay (Abbott Molecular Inc.).
• Age 18 years or older at the time of informed consent.
• Patients must have NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose
• Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC
• Patients must have a tumor tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.
• Patients must have recovered from all toxicities related to prior anticancer therapies to grade ≤ 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study.

Exclusion criteria:

• Patients with known hypersensitivity to any of the excipients of LDK378.
• Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
• History of carcinomatous meningitis.
• Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
• Clinically significant, uncontrolled heart disease
• Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug.