LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.

Study Overview
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Brief Summary
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This was a single-arm, open-label, multicenter, phase II study to evaluate the efficacy and safety of the ALK inhibitor LDK378 when used as single agent in patients with ALK-rearranged stage IIIB or IV NSCLC previously treated with alectinib. Treatment with LDK378 750 mg qd continued until the patient experienced disease progression as determined by the investigator according to RECIST 1.1, unacceptable toxicity that precluded further treatment, pregnancy, start of a new anticancer therapy, discontinued treatment at the discretion of the patient or investigator, lost to follow-up, death, or study was terminated by Sponsor.

Detailed Description
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Study completed as per protocol. 'Switched to commercial drug' implies that after the primary and secondary objectives were achieved, one patient continued the study treatment as they did not meet the progression disease or AE to be discontinued from the treatment. But after the regulatory approval, Novartis decided to close the study, the 1 patient switched to commercially available drug.

Official Title
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A Phase II, Multi-center, Open-label, Single-Arm Study to Evaluate the Efficacy and Safety of Oral LDK378 Treatment for Patients With ALK-Positive Non-Small Cell Lung Cancer Previously Treated With Alectinib

Conditions
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Non-Small-Cell Lung Cancer

Intervention / Treatment
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* Drug: LDK378


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically confirmed diagnosis of Stage IIIb or IV NSCLC that carries an ALK rearrangement as determined locally by Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test. Patients must have NSCLC that has progressed at study enrollment. Patients must have received previous treatment with alectinib for treatment of locally advanced or metastatic NSCLC. Prior therapy with crizotinib as ALK inhibitor therapy in addition to alectinib is allowed. Alectinib doesn't need to be the last therapy prior to study enrollment. No particular sequence of prior alectinib and crizotinib is required for enrollment. Patients must be chemotherapy-naïve or have received only one line of prior cytotoxic chemotherapy. Age 18 years or older at the time of informed consent. Key Exclusion Criteria: Patients with known hypersensitivity to any of the excipients of LDK378. Prior therapy with other ALK inhibitor investigational agents except crizotinib and alectinib. Prior systemic anti-cancer (including investigational) therapy aside from alectinib, crizotinib and one regimen of previous cytotoxic chemotherapy for locally advanced or metastatic NSCLC. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms. Patient with history of interstitial lung disease or interstitial pneumonitis, including clinically significant radiation pneumonitis. Patients with history of carcinomatous meningitis. Patient with a concurrent malignancy or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. Patient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LDK378 (Ceritinib)<br>Participants who received LDK378 750mg once daily on a 28 day cycle. | Drug: LDK378<br>* Oral LDK378 750mg once daily<br>* Other names: Oral LDK378 750mg once daily;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) to LDK378 by Investigator Assessment | ORR, defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) in the whole body as assessed per RECIST 1.1 by the investigator. CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. | Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | DCR, calculated as the percentage of participants with best overall response of CR, PR, or stable disease (SD) evaluated by investigator per RECIST 1.1; CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD); PD: taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. | 6 cycles of 28 days up to 798 days | 
| Time to Tumor Response (TTR) | TTR, calculated as the time from first dose of LDK378 to first documented response (CR or PR) evaluated by investigator per RECIST 1.1 for participants with confirmed PR or CR. | 6 cycles of 28 days up to 798 days | 
| Duration of Response (DOR) | DOR, calculated as the time from the date of the first documented response (CR or PR) to the first documented disease progression evaluated by investigator per RECIST 1.1 or death due to any cause | 6 cycles of 28 days up to 798 days | 
| Progression Free Survival (PFS) | PFS, calculated as the time from first dose of LDK378 to date of first documented disease progression evaluated by investigator per RECIST 1.1 or date of death due to any cause | 6 cycles of 28 days up to 798 days | 
| Overall Survival (OS) | OS was defined as the time from the start date of study drug to the date of death due to any cause. | 6 cycles of 28 days up to 798 days | 
| Overall Intracranial Response Rate (OIRR) | OIRR, calculated as the percentage of participants with a best overall confirmed response of CR or PR in the brain assessments for participants having measurable brain metastases at baseline | 6 cycles of 28 days up to 798 days | 

 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, alectinib, Non-small cell lung carcinoma (NSCLC), lung cancer, lung adenocarcinoma, Non small cell lung carcinoma, Non small cell lung cancer, Non-small cell lung cancer