Trial Outcomes & Findings for LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib. (NCT NCT02450903)
NCT ID: NCT02450903
Last Updated: 2021-03-30
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 days
Results posted on
2021-03-30
Participant Flow
Approximately 20 patients were planned to be enrolled.
A total of 20 patients were enrolled and treated with ceritinib.
Participant milestones
| Measure |
LDK378 (Ceritinib)
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
Entered Post-treatment Effic. f/u Phase
|
4
|
|
Overall Study
Entered Survival Follow-up Phase
|
15
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
20
|
Reasons for withdrawal
| Measure |
LDK378 (Ceritinib)
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Progressive disease
|
15
|
|
Overall Study
Switched to commercial drug
|
1
|
|
Overall Study
Subject/guardian decision
|
1
|
Baseline Characteristics
LDK378 in Patients With ALK Positive NSCLC Previously Treated With Alectinib.
Baseline characteristics by cohort
| Measure |
LDK378 (Ceritinib)
n=20 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Age, Continuous
|
52.2 Years
STANDARD_DEVIATION 15.88 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
19 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Until disease progression or unacceptable toxicity occurs, or patient withdrawal up to 798 daysPopulation: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.
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.
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=20 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Overall Response Rate (ORR) to LDK378 by Investigator Assessment
|
25.0 Percentage of participants
Interval 8.7 to 49.1
|
SECONDARY outcome
Timeframe: 6 cycles of 28 days up to 798 daysPopulation: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.
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.
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=20 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Disease Control Rate (DCR)
|
70.0 Percentage of participants
Interval 45.7 to 88.1
|
SECONDARY outcome
Timeframe: 6 cycles of 28 days up to 798 daysPopulation: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib - participants with confirmed PR or CR.
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.
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=5 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Time to Tumor Response (TTR)
|
1.8 Months
Standard Deviation 0.0818
|
SECONDARY outcome
Timeframe: 6 cycles of 28 days up to 798 daysPopulation: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib - participants with confirmed PR or CR.
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
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=5 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Duration of Response (DOR)
|
6.3 Months
Interval 3.5 to 9.2
|
SECONDARY outcome
Timeframe: 6 cycles of 28 days up to 798 daysPopulation: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.
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
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=20 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Progression Free Survival (PFS)
|
3.7 Months
Interval 1.9 to 5.3
|
SECONDARY outcome
Timeframe: 6 cycles of 28 days up to 798 daysPopulation: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib.
OS was defined as the time from the start date of study drug to the date of death due to any cause.
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=20 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Overall Survival (OS)
|
17.3 Months
Interval 9.1 to
N/A= not enough number of events to calculate the upper limit of the confidence interval.
|
SECONDARY outcome
Timeframe: 6 cycles of 28 days up to 798 daysPopulation: Full Analysis Set (FAS) consists of all patients who received at least one dose of ceritinib - participants with measurable brain disease at baseline
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
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=2 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Overall Intracranial Response Rate (OIRR)
|
0.0 Percentage of participants
Interval 0.0 to 84.2
|
POST_HOC outcome
Timeframe: approx. 24 months, approx. 33 monthsPopulation: Clinical Database Population: all treated patients and patients who died during screening
On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months). Deaths post treatment survival follow up were collected after the on treatment period, up to 33 months. Patients who didn't die during the on-treatment period and had not stopped study participation at the time of data cut-off (end of study) were censored.
Outcome measures
| Measure |
LDK378 (Ceritinib)
n=20 Participants
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
All Collected Deaths
Deaths post-treatment survival follow-up
|
12 Participants
|
|
All Collected Deaths
Total Deaths
|
12 Participants
|
|
All Collected Deaths
Deaths on-treatment
|
0 Participants
|
Adverse Events
LDK378 (Ceritinib)
Serious events: 9 serious events
Other events: 20 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
LDK378 (Ceritinib)
n=20 participants at risk
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Hepatobiliary disorders
Hepatobiliary disease
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Infections and infestations
Pneumonia
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Metabolism and nutrition disorders
Dehydration
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Renal and urinary disorders
Acute kidney injury
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Vascular disorders
Embolism
|
5.0%
1/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
Other adverse events
| Measure |
LDK378 (Ceritinib)
n=20 participants at risk
Participants who received LDK378 750mg once daily on a 28 day cycle.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Gastrointestinal disorders
Constipation
|
35.0%
7/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
85.0%
17/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Gastrointestinal disorders
Nausea
|
80.0%
16/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Gastrointestinal disorders
Vomiting
|
65.0%
13/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
General disorders
Fatigue
|
15.0%
3/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
General disorders
Pyrexia
|
25.0%
5/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Infections and infestations
Nasopharyngitis
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Infections and infestations
Upper respiratory tract infection
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Alanine aminotransferase increased
|
40.0%
8/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Amylase increased
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Aspartate aminotransferase increased
|
35.0%
7/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Blood alkaline phosphatase increased
|
15.0%
3/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Blood cholesterol increased
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Blood creatinine increased
|
45.0%
9/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Electrocardiogram QT prolonged
|
25.0%
5/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Gamma-glutamyltransferase increased
|
25.0%
5/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Lymphocyte count decreased
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Weight decreased
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
Weight increased
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Investigations
White blood cell count decreased
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Metabolism and nutrition disorders
Decreased appetite
|
40.0%
8/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Nervous system disorders
Dysgeusia
|
15.0%
3/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Rash
|
15.0%
3/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
10.0%
2/20 • On treatment deaths were collected from FPFT up to 30 days after study drug discontinuation, for a maximum duration of 24 months (treatment duration ranged from 0.4 to to 23.0 months).
AE: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER