Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell lung Cancer, NSCLC, ALK, LDK378, ALK-rearranged, ALK-positive, advanced non-small cell lung cancer
Brief summary
A single-Arm, open-label, multi-center, phase I/II study in which the pharmacokinetics, safety, tolerability and efficacy of LDK378 will be assessed in adult Chinese patients with locally advanced or metastatic NSCLC harboring a confirmed ALK rearrangement. Patients must have demonstrated progression during or after crizotinib treatment whether or not previously treated with cytotoxic chemotherapy. Approximately 100 patients will be enrolled. For the first 15 patients enrolled in this study, patients will have an additional 5-day PK run-in period before treatment period. The pharmacokinetics profile of LDK378 in Chinese adult patients with ALK-rearranged NSCLC will be evaluated.
Detailed description
This is a phase I/II, open-label, multi-center study in which the PK, safety, tolerability and efficacy of LDK378 will be assessed in adult Chinese patients with locally advanced or metastatic NSCLC harboring a confirmed ALK rearrangement (positive) as assessed using the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) or positive as assessed by immunohistochemistry (IHC) test (Ventana Medical Systems, Inc) using rabbit monoclonal primary antibody assay (D5F3). Patients must have demonstrated progression during or after crizotinib treatment whether or not previously treated with cytotoxic chemotherapy. Approximately 100 patients with locally advanced or metastatic NSCLC which carry ALK -rearrangement will be enrolled in the study. The first 15 patients to be enrolled in the study will have PK sampling over 120-hour during the 5-day PK run-in period following a single oral dose at 750 mg. After the PK run-in period, the treatment period will start in which LDK378 will be given starting on Cycle 1 Day 1 in a continuous daily oral dosing in 28-day cycles. Separated from these 15 patients, the rest of the enrolled patients will receive LDK378 treatment at 750 mg QD on Cycle 1 Day 1. Tumor response will be evaluated every 8 weeks (i.e. every 2 cycles) starting from the first day of treatment with LDK378 until the time of RECIST-defined PD by investigator assessment, withdrawal of consent for further follow-up, loss to follow-up or death.
Interventions
DRUGLDK378
750 mg once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed diagnosis of NSCLC that carries an ALK rearrangement defined as positive using the FDA approved Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular Inc.) test and scoring algorithm (including positivity criteria) or positive as assessed by the CFDA approved immunohistochemistry (IHC) test (Ventana Medical Systems, Inc) * Age 18 years or older at the time of informed consent. * Patients must have stage IIIB or IV NSCLC at the time of study entry and have had progressive disease during or after crizotinib treatment whether or not previously treated with cytotoxic chemotherapy. If treated with chemotherapy, maximum 2 lines are allowed.
Exclusion criteria
* Patients with known hypersensitivity to any of the excipients of LDK378 * 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 * History of carcinomatous meningitis * Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years. * clinically significant, uncontrolled heart disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf | PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) | AUClast: The area under the concentration-time curve from time zero to the last measurable concentration time. AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours. AUCinf: Area under the plasma (serum, or blood) concentration versus time curve from time zero to infinity |
| Primary Pharmacokinetics (PK) Parameter of of LDK378 After Daily Oral Dose: AUC0-24h | Cycle 2 Day 1 (after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h) | AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours. |
| Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax | PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h) | Cmax is the maximum (peak) concentration of drug in plasma |
| Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax | PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h) | Tmax is the time to reach maximum plasma concentration. |
| Overall Summary of Adverse Events (AEs) - Per Occurence | up to 41 months | Safety and tolerability of LDK378 at 750 mg once daily dose in Chinese adult patients with ALK-rearranged locally advanced or metastatic NSCLC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Intracranial Response Rate (OIRR) Per Investigator Assessment | 40 months | OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Overall Intracranial Response Rate (OIRR) Per BIRC Assessment | 40 months | OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Progression Free Survival (PFS) Per Investigator Assessment | 40 months | PFS, defined as time from first dose of LDK378 to progression or death due to any cause. |
| Overall Survival (OS) | 40 months | OS, defined as time from first dose of LDK378 to death due to any cause. |
| Overall Response Rate (ORR) Per RECIST 1.1 Per Investigator Assessment | 40 months | ORR calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Disease Control Rate (DCR) Per BIRC Assessment | 40 months | DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is 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, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline. |
| Time to Response (TTR) Per BIRC Assessment | 40 months | TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Progression Free Survival (PFS) Per BIRC Assessment | 40 months | PFS, defined as time from first dose of LDK378 to progression or death due to any cause. |
| Duration of Response (DOR) Per BIRC Assessment | 40 months | DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is 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 Per Blind Independent Review Committee (BIRC) Assessment | 40 months | ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Duration of Response (DOR) Per Investigator Assessment | 40 months | DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
| Disease Control Rate (DCR) Per Investigator Assessment | 40 months | DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is 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, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline. |
| Time to Response (TTR) Per Investigator Assessment | 40 months | TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. |
Countries
China
Participant flow
Recruitment details
Approximately 100 patients were planned to be enrolled, and 103 patients were actually enrolled and analyzed.
Pre-assignment details
Not Completed means that the participants discontinued from the treatment phase
Participants by arm
| Arm | Count |
|---|---|
| LDK378 daily dosing, 28-day cycle patients | 103 |
| Total | 103 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 7 |
| Overall Study | Completed treatment phase | 6 |
| Overall Study | Death | 13 |
| Overall Study | Lost to Follow-up | 3 |
| Overall Study | Physician Decision | 6 |
| Overall Study | Progressive disease | 58 |
| Overall Study | Subject/guardian decision | 10 |
Baseline characteristics
| Characteristic | LDK378 |
|---|---|
| Age, Continuous | 49.3 Years STANDARD_DEVIATION 10.89 |
| Race/Ethnicity, Customized Chinese | 103 Participants |
| Sex: Female, Male Female | 48 Participants |
| Sex: Female, Male Male | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 23 / 103 |
| other Total, other adverse events | 101 / 103 |
| serious Total, serious adverse events | 36 / 103 |
Outcome results
Primary
Overall Summary of Adverse Events (AEs) - Per Occurence
Safety and tolerability of LDK378 at 750 mg once daily dose in Chinese adult patients with ALK-rearranged locally advanced or metastatic NSCLC
Time frame: up to 41 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | All deaths | 65 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | On-treatment deaths | 23 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | Adverse Events (AEs) | 103 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | AEs suspected to be drug related | 100 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | Serious Adverse Events (SAEs) | 36 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | SAEs suspected to be drug related | 7 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | AEs leading to discontinuation | 15 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | AEs requiring dose adjustment or interruption | 64 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | AEs requiring dose interruption | 34 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | AEs requiring dose adjustment | 49 occurrences |
| LDK378 | Overall Summary of Adverse Events (AEs) - Per Occurence | AEs requiring additional therapy | 94 occurrences |
Primary
Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax
Cmax is the maximum (peak) concentration of drug in plasma
Time frame: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)
Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LDK378 | Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax | PK run-in phase | 233 ng/mL | Geometric Coefficient of Variation 52.2 |
| LDK378 | Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Cmax | C2D1 | 1080 ng/mL | Geometric Coefficient of Variation 78 |
Primary
Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax
Tmax is the time to reach maximum plasma concentration.
Time frame: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose)) and C2D1(after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)
Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| LDK378 | Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax | PK run-in phase | 5.94 hour |
| LDK378 | Primary Pharmacokinetics (PK) Parameter of LDK378 After Daily Oral Dose: Tmax | C2D1 | 5.88 hour |
Primary
Primary Pharmacokinetics (PK) Parameter of of LDK378 After Daily Oral Dose: AUC0-24h
AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours.
Time frame: Cycle 2 Day 1 (after one cycle (28 days) of continous dosing)(0h, 1h, 2h, 3h, 4h , 6h , 8h and 24h)
Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LDK378 | Primary Pharmacokinetics (PK) Parameter of of LDK378 After Daily Oral Dose: AUC0-24h | 22000 ng*hr/mL | Geometric Coefficient of Variation 79.7 |
Primary
Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf
AUClast: The area under the concentration-time curve from time zero to the last measurable concentration time. AUC0-24h: The area under the plasma concentration-time curve calculated from time zero to 24 hours. AUCinf: Area under the plasma (serum, or blood) concentration versus time curve from time zero to infinity
Time frame: PK run-in phase (0h, 1h, 2h, 3h, 4h, 6h, 8h, 24h, 48h, 72h, 96h after PK run-in dose and predose Cycle 1 day 1 (C1D1)(approximately 120h after PK run in dose))
Population: The Pharmacokinetic Analysis Set (PAS) consists of all patients who receive at least one dose of LDK378 and provide at least one evaluable PK sample.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LDK378 | Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf | AUClast | 10100 ng*hr/mL | Geometric Coefficient of Variation 52.6 |
| LDK378 | Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf | AUC0-24h | 3940 ng*hr/mL | Geometric Coefficient of Variation 49.6 |
| LDK378 | Primary Pharmacokinetics (PK) Parameters of of LDK378 After Daily Oral Dose: AUClast, AUC0-24h, AUCinf | AUCinf | 11100 ng*hr/mL | Geometric Coefficient of Variation 57.7 |
Secondary
Disease Control Rate (DCR) Per BIRC Assessment
DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is 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, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDK378 | Disease Control Rate (DCR) Per BIRC Assessment | 67.0 Percentage of participants |
Secondary
Disease Control Rate (DCR) Per Investigator Assessment
DCR, calculated as the percentage of participants with best overall response of CR, PR, stable disease (SD) and Non-CR/Non-progressive disease (PD). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD is 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, the sum must also demonstrate an absolute increase of at least 5 mm. SD is neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Non-CR/Non-PD refers to best overall responses that are neither CR nor PD per RECIST 1.1 criteria for patients with non-measurable disease only at baseline.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDK378 | Disease Control Rate (DCR) Per Investigator Assessment | 77.7 Percentage of participants |
Secondary
Duration of Response (DOR) Per BIRC Assessment
DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDK378 | Duration of Response (DOR) Per BIRC Assessment | 9.2 months |
Secondary
Duration of Response (DOR) Per Investigator Assessment
DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or all cause death. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDK378 | Duration of Response (DOR) Per Investigator Assessment | 7.5 months |
Secondary
ORR Per RECIST 1.1 Per Blind Independent Review Committee (BIRC) Assessment
ORR per RECIST 1.1 calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDK378 | ORR Per RECIST 1.1 Per Blind Independent Review Committee (BIRC) Assessment | 32.0 Percentage of participants |
Secondary
Overall Intracranial Response Rate (OIRR) Per BIRC Assessment
OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDK378 | Overall Intracranial Response Rate (OIRR) Per BIRC Assessment | 0 Percentage of participants |
Secondary
Overall Intracranial Response Rate (OIRR) Per Investigator Assessment
OIRR calculated as the ORR (CR+PR) of lesions in the brain for patients who have measureable disease in the brain at baseline. CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDK378 | Overall Intracranial Response Rate (OIRR) Per Investigator Assessment | 39.1 Percentage of participants |
Secondary
Overall Response Rate (ORR) Per RECIST 1.1 Per Investigator Assessment
ORR calculated as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LDK378 | Overall Response Rate (ORR) Per RECIST 1.1 Per Investigator Assessment | 41.7 Percentage of participants |
Secondary
Overall Survival (OS)
OS, defined as time from first dose of LDK378 to death due to any cause.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDK378 | Overall Survival (OS) | 17.5 Months |
Secondary
Progression Free Survival (PFS) Per BIRC Assessment
PFS, defined as time from first dose of LDK378 to progression or death due to any cause.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDK378 | Progression Free Survival (PFS) Per BIRC Assessment | 3.8 Months |
Secondary
Progression Free Survival (PFS) Per Investigator Assessment
PFS, defined as time from first dose of LDK378 to progression or death due to any cause.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDK378 | Progression Free Survival (PFS) Per Investigator Assessment | 7.2 Months |
Secondary
Time to Response (TTR) Per BIRC Assessment
TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDK378 | Time to Response (TTR) Per BIRC Assessment | 1.80 Months |
Secondary
Time to Response (TTR) Per Investigator Assessment
TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR). CR is the 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 is at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time frame: 40 months
Population: The Full Analysis Set (FAS) consisted of enrolled patients who received at least one dose of ceritinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LDK378 | Time to Response (TTR) Per Investigator Assessment | 1.90 Months |