Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Carcinoma, Non-Small-Cell Lung

Neoplasm Metastasis

Carcinoma

Lung Neoplasms

Adenocarcinoma

Adenocarcinoma of Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lung Adenocarcinoma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Crizotinib

Ceritinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants on this arm took oral LDK378 750 mg once daily.

LDK378/Ceritinib was supplied as 150 mg hard gelatin capsules and administered orally

LDK378

Novartis Pharmaceuticals

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).

LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

A Phase II, Multicenter, Single-arm Study of Oral LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed 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.

ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response (OR) defined as complete response (CR) or partial response (PR) as assessed by BIRC. 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.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by investigator assessment 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.

DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to any cause, by BIRC assessment 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.

DCR per RECIST 1.1 is the percentage of participants with best overall response of CR, PR, stable disease (SD) or Non-CR/Non-PD. CR: Disappearance of all non-nodal target lesions. Also, 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 that would qualify for PD. PD: At least a 20% increase in the sum of diameter of all measured target lesions, 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 5mm.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator. This was only on participants with confirmed CR or PR. 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.

TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by BIRC assessment. This was only on participants with confirmed CR or PR. 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.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by investigator.

OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline by BIRC.

PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by investigator and BIRC assessments.

OS, defined as time from first dose of LDK378 to death due to any cause

LDK378 Ceritinib)

LDK378 (Ceritinib)

Age, Continuous

Sex: Female, Male

Asian

Caucasian

Black

Other

Race/Ethnicity, Customized

The Full Analysis Set (FAS) consisted of all patients who received at least one dose of study drug.

Study Director

Overall Response Rate (ORR) by Investigator Assessment

ORR by Blinded Independent Review Committee (BIRC)

The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) by investigator.

Duration of Response (DOR) as Per Investigator

The set consisted of patients in the Full Analysis Set (FAS) who had confirmed complete response (CR) or partial response (PR) as assessed by BIRC.

Duration of Response (DOR) as Per BIRC

DCR per Investigator

DCR per BIRC

Disease Control Rate (DCR) as Per Investigator and BIRC

Time to Response (TTR) as Per Investigator

Time to Response (TTR) as Per BIRC

The set consisted of patients in the Full Analysis Set (FAS) who had measurable target lesions in brain at baseline by investigator.

Overall Intracranial Response Rate (OIRR) as Per Investigator

The set consisted of patients in the Full Analysis Set (FAS) who had measurable target lesions in brain at baseline by BIRC.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer	NCT01685138	Non-Small Cell ...	LDK378	18 Years -	Novartis
LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer	NCT01685138	Non-Small Cell ...	LDK378	18 Years -	Novartis
LDK378 in Crizotinib naïve Adult Patients With ALK-activated Non-small Cell Lung Cancer	NCT01685138	Non-Small Cell ...	LDK378	18 Years -	Novartis

Spots Global Cancer Trial Database for crizotinib naïve adult patients