LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The primary purpose of the study was to compare the antitumor activity of LDK378 versus reference chemotherapy. 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.

Official Title
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A Phase III Multicenter, Randomized Study of Oral LDK378 Versus Standard Chemotherapy in Previously Untreated Adult Patients With ALK Rearranged (ALK-positive), Stage IIIB or IV, Non-squamous Non-small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Ceritinib
* Drug: Pemetrexed
* Drug: Cisplatin
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has a histologically or cytologically confirmed diagnosis of non-squamous Non-small cell lung cancer (NSCLC) that is Anaplastic lymphoma kinase (ALK) positive as assessed by the Ventana Immunohistochemistry (IHC) test. The test will be performed at Novartis designated central laboratories. Patient has newly diagnosed stage IIIB (who are not a candidate for definitive multimodality therapy) or stage IV NSCLC or relapsed locally advanced or metastatic NSCLC not previously treated with any systemic anti-cancer therapy (e.g. cytotoxic drugs, monoclonal antibody therapy, crizotinib or other ALK inhibitors, or other targeted therapies, either experimental or not), with exception of neo-adjuvant or adjuvant therapy Patient has at least one measurable lesion as defined by RECIST 1.1. Exclusion Criteria: Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate) Patient with a history of severe hypersensitivity reaction to platinum containing drugs, pemetrexed or any known excipients of these drugs. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ceritinib<br>Ceritinib patients were on continuous oral dosing of ceritinib 750 mg once daily in fasted state. | Drug: Ceritinib<br>* Ceritinib was administered orally once-daily fasted at a dose of 750 mg capsules on a continuous dosing schedule. Ceritinib (LDK378) was the investigational treatment and is referred to as the investigational study treatment/drug.<br>* Other names: LDK378;|
| Active Comparator: Chemotherapy<br>Chemotherapy patients (Induction per Investigator's choice) were on four 21-day cycles of Pemetrexed 500mg/m2 iv + Cisplatin 75 mg/m2 or Pemetrexed 500 mg/m2 iv + Carboplatin AUC 5-6 iv followed by Pemetrexed 500 mg/m2 every 21 days followed by Pemetrexed maintenance in non-progressors, etc (other usual rule to stop treatment). | Drug: Pemetrexed<br>* Pemetrexed was administered at a dose of 500 mg/m2 as an iv infusion on Day 1 of each 21-day cycle to patients randomized to the chemotherapy arm.<br>Drug: Cisplatin<br>* Cisplatin was administered by IV at a dose of 75 mg/m2 every 21 days for up to 4 cycles.<br>Drug: Carboplatin<br>* Carboplatin was administered as iv infusion (AUC 5-6) every 21 days up to 4 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) | PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of death due to any cause | from the date of randomization to the date of first radiologically documented disease progression or death due to any cause (assessed every 6 weeks up to approximately 34 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS defined as time from date of randomization to date of death due to any cause | From randomization until death (up to approximately 34 months) | 
| Overall Response Rate (ORR) | ORR defined as the proportion of patients with a best overall response defined as Complete Response (CR) or Partial Response (PR) as evaluated by Blinded Independent Review Committee (BIRC) and by investigator assessment per RECIST 1.1 | From randomization until death (up to approximately 34 months) | 
| Duration of Response (DOR) | DOR defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause | From randomization until death (up to approximately 34 months) | 
| Disease Control Rate (DCR) | DCR defined as the proportion of patients with best overall response of CR, PR, or Stable Disease (SD) | From randomization until death (up to approximately 34 months) | 
| Time to Response (TTR) | TTR defined as the time from date of randomization to date of first documented response (CR or PR) | From randomization until death (up to approximately 34 months) | 
| Patient Reported Outcomes | The time to definitive deterioration from the date of randomization to the date of event for disease related symptoms. | Screening, followed by every 6 weeks until Month 33 after Month 33 every 9 weeks. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, NSCLC, 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, non-squamous non-small cell lung cancer