A Phase III, Multicenter, Randomized, Open-label Study of Oral LDK378 Versus Standard Chemotherapy in Adult Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer Who Have Been Treated Previously With Chemotherapy (Platinum Doublet) and Crizotinib

Study design:

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Study Objectives:

Primary Outcome Measures:

• Progression Free Survival (PFS) [ Time Frame: Month 18 ] [ Designated as safety issue: No ]  PFS which is defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.

Secondary Outcome Measures:

• Overall Survival (OS) [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
OS defined as time from date of randomization to date of death due to any cause

• Overall Response Rate (ORR) [ Time Frame: Month 18 ] [ Designated as safety issue: No ] ORR is defined as the proportion of patients with a best overall response defined as complete response (CR) or partial response (PR); (CR+PR)

• Duration of Response (DOR) [ Time Frame: Month 18 ] [ Designated as safety issue: No ] DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to underlying cancer

• Disease Control Rate (DCR) [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
DCR is defined as the proportion of patients with best overall response of CR, PR, or stable disease (SD)

• Time to response (TTR) [ Time Frame: Month 18 ] [ Designated as safety issue: No ]
TTR is defined as the time from date of randomization to date of first documented response (CR or PR)

Participation conditions

Inclusion Criteria:

1. Patient has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as assessed by the FDA approved Abbott FISH Test.
2. Patient has stage IIIB or IV diagnosis and must have received one or two prior regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of locally advanced or metastatic NSCLC.
3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation

Exclusion Criteria:

1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
2. Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel 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.

Centre Hospitalier de Luxembourg - CHL