LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

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

A single-arm, open-label, two-stage multicenter, phase II study. Patients were pre-screened for ALK positive status. Treatment with LDK378 at 750 mg qd was continued until the patient experienced unacceptable toxicity that precluded further treatment, discontinued treatment at the discretion of the investigator or patient, started a new anticancer therapy and/or died. LDK378 was 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. 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. Male and female patients aged 18 or over with ALK-rearranged non-small cell cancer (NSCLC) were screened for eligibility. Patients had to have received no prior crizotinib, and had to be chemotherapy-naïve or been pretreated with cytotoxic chemotherapy (up to three prior lines).

Key Inclusion criteria:

• Histologically or cytologically confirmed diagnosis of stage IIIB or IV NSCLC that carried an ALK rearrangement, as per the FDA-approved Vysis ALK break-apart FISH assay (Abbott Molecular Inc.)
• Age 18 years or older at the time of informed consent.
• Patients must have NSCLC that had progressed during or after the last chemotherapy regimen received prior to the first dose of LDK378, if chemotherapy was received
• Patients must have been chemotherapy-naive or had received 1-3 lines of cytotoxic chemotherapy to treat their locally advanced or metastatic NSCLC
• Patients must have had 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 were not allowed to participate in the study.

Key Exclusion criteria:

• Prior treatment with crizotinib, or any other ALK inhibitor investigational agent, for NSCLC
• Patients with known hypersensitivity to any of the excipients of LDK378.
• Patients with symptomatic central nervous system (CNS) metastases who were neurologically unstable or had 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.