Conditions: Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer ALK LDK378 Non-small cell lung carcinoma (NSCLC) treatment of lung cancer after first metastasis lung cancer lung adenocarcinoma Non small cell lung carcinoma Non small cell lung cancer NSCLC chemotherapy ALK-positive ALK-rearranged advanced non-small cell lung cancer crizotinib
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 231
Healthy volunteers: no

Brief summary:
The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib. Patients in the chemotherapy arm were given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.

Detailed description:
A total of 231 patients were randomized to one of the two treatment arms in a 1:1 ratio. Randomization was stratified by World Health Organization (WHO) performance status (0 versus 1-2) and whether the patient had brain metastases at screening. The study was planned to be ended once the final overall survival (OS) analysis was performed (at the earliest of approximately 196 deaths observed or statistical significance reached at earlier OS interim analysis).

Following an agreement between Novartis and European Medicines Agency (EMA) in May 2023 to terminate the trial earlier, this study was completed when the total number of deaths was 190. Patients who had Response Evaluation Criteria In Solid Tumors (RECIST)-defined disease progression as confirmed by the Blinded Independent Review Committee (BIRC), but who, in the opinion of the Investigator, had continued clinical benefit from study treatment on either the chemotherapy arm or the ceritinib arm, continued to receive treatment. These patients continued assessments in the treatment phase. In addition, only patients randomized to the chemotherapy arm were allowed to crossover to receive ceritinib therapy (extension treatment \[ET\] phase) after BIRC-confirmed, RECIST-defined disease progression, and provided they met the eligibility requirements.

Arms:
arm 1: Ceritinib 750 mg arm 2: Chemotherapy as determined by BIRC

Interventions: intervention 1: Ceritinib intervention 2: Pemetrexed intervention 3: Docetaxel
Intervention descriptions: intervention 1: Ceritinib was the investigational treatment and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily. intervention 2: Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m\^2 every 21 days. intervention 3: Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m\^2 every 21 days.

Protocol document: