LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer
Condition: Non-Small Cell Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: LDK378
Intervention description: LDK378/Ceritinib was supplied as 150 mg hard gelatin capsules and administered orally
Intervention MeSH terms: Ceritinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 124.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Non-Small Cell Lung Cancer; Non small cell lung carcinoma; NSCLC; ALK; LDK378; Ceritinib; crizotinib naïve adult patients; ALK-activated non-small cell lung cancer; treatment of lung cancer after first metastasis; lung cancer; lung adenocarcinoma

Summary:

      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).
    

Eligibility criteria:

        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.