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NCT01828099

LDK378 Versus Chemotherapy in Previously Untreated Patients With ALK Rearranged Non-small Cell Lung Cancer

Completed Phase 3 Results posted Last updated 16 January 2025
What this trial tests

Phase 3 trial testing Ceritinib in Non-Small Cell Lung Cancer in 376 participants. Completed in 7 January 2024.

Timeline
9 July 2013
Primary endpoint
24 June 2016
7 January 2024

Quick facts

Lead sponsorNovartis Pharmaceuticals
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment376
Start date9 July 2013
Primary completion24 June 2016
Estimated completion7 January 2024
Sites167 locations across Italy, Colombia, Japan, Taiwan, Ireland, Poland, South Korea, Lebanon

Drugs / interventions tested

Conditions studied

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

Adults 18 to 100, any sex, with Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC) Primary · From the date of randomization to the date of first radiologically documented disease progression or death due to any cause, up to approximately 34 months

PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression (as assessed by BIRC per RECIST 1.1) or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or had received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. The distribution of PFS was estimated using the Kaplan-Meier (KM) method.

GroupValue95% CI
Ceritinib16.612.6 – 27.2
Chemotherapy8.15.8 – 11.1
Overall Survival (OS) Secondary · From date of randomization to date of death due to any cause, up to approximately 120 months

OS defined as time from date of randomization to date of death due to any cause. If the patient was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cut-off date. The distribution of OS was estimated using the KM method.

GroupValue95% CI
Ceritinib62.944.2 – 77.6
Chemotherapy40.728.5 – 54.5
Overall Response Rate (ORR) by BIRC Assessment Secondary · Up to approximately 34 months

ORR is defined as the percentage of patients with a best overall response defined as complete response (CR) or or partial response (PR) measured by BIRC 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.

GroupValue95% CI
Ceritinib72.565.5 – 78.7
Chemotherapy26.720.5 – 33.7
Overall Response Rate (ORR) by Investigator Assessment Secondary · Up to approximately 120 months

ORR is defined as the percentage of patients with a best overall response defined as complete response (CR) or or partial response (PR) measured 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.

GroupValue95% CI
Ceritinib73.566.7 – 79.7
Chemotherapy33.226.5 – 40.4
Duration of Response (DOR) by BIRC Assessment Secondary · From first documented response to first documented disease progression or death, assessed up to approximately 34 months

DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression (measured by BIRC assessment per RECIST 1.1) or death due to any cause. CR: Disappearance of all lesions with lymph nodes measuring \< 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. If a patient had not had an event, DOR was censored at the date of last adequate tumor assessment. Patients who had never achieved a best overall response of CR or PR were excluded from the analysis. The distribution f

GroupValue95% CI
Ceritinib23.916.6 – NA
Chemotherapy11.17.8 – 16.4
Duration of Response (DOR) by Investigator Assessment Secondary · From first documented response to first documented disease progression or death, assessed up to approximately 120 months

DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression (measured by investigator assessment per RECIST 1.1) or death due to any cause. CR: Disappearance of all lesions with lymph nodes measuring \< 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. If a patient had not had an event, DOR was censored at the date of last adequate tumor assessment. Patients who had never achieved a best overall response of CR or PR were excluded from the analysis. The distr

GroupValue95% CI
Ceritinib22.617.7 – 26.2
Chemotherapy9.86.1 – 16.9
Disease Control Rate (DCR) by BIRC Assessment Secondary · Up to approximately 34 months

DCR is defined as the percentage of patients with best overall response of CR, PR, or stable disease (SD) measured by BIRC assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 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.

GroupValue95% CI
Ceritinib84.778.7 – 89.5
Chemotherapy73.866.9 – 79.9
Disease Control Rate (DCR) by Investigator Assessment Secondary · Up to approximately 120 months

DCR is defined as the percentage of patients with best overall response of CR, PR, or stable disease (SD) measured by investigator assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 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.

GroupValue95% CI
Ceritinib89.484.1 – 93.4
Chemotherapy75.969.2 – 81.9
Time to Response (TTR) by BIRC Assessment Secondary · From randomization to date of first documented response, up to approximately 34 months

TTR is defined as the time from date of randomization to date of first documented response (CR or PR) measured by BIRC assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 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. Patients who had not achieved a confirmed CR or PR were censored at the last adequate tumor assessment date when they had not had a PFS event or at maximum follow-up when they had had a PFS event.

GroupValue95% CI
Ceritinib6.145.1 – 61.7
Chemotherapy13.365.1 – 90.1
Time to Response (TTR) by Investigator Assessment Secondary · From randomization to date of first documented response, up to approximately 120 months

TTR is defined as the time from date of randomization to date of first documented response (CR or PR) measured by investigator assessment per RECIST 1.1. CR: Disappearance of all lesions with lymph nodes measuring \< 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. Patients who had not achieved a confirmed CR or PR were censored at the last adequate tumor assessment date when they had not had a PFS event or at maximum follow-up when they had had a PFS event

GroupValue95% CI
Ceritinib6.295.1 – 71.9
Chemotherapy12.714.7 – 461.6
PFS by Investigator Assessment Secondary · From the date of randomization to the date of first radiologically documented disease progression or death due to any cause, up to approximately 120 months

PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression (as assessed by investigator assessment per RECIST 1.1) or death due to any cause. A patient who had not progressed or died at the date of the analysis cut-off or had received another anticancer therapy had their PFS censored at the time of the last adequate tumor evaluation before the earlier of the cut-off date or the anticancer therapy date. The distribution of PFS was estimated using the KM method.

GroupValue95% CI
Ceritinib16.813.5 – 22.8
Chemotherapy7.25.8 – 9.7
Overall Intracranial Response Rate (OIRR) Secondary · Up to approximately 34 months

OIRR is defined as the ORR based on lesions in brain (target, non-target lesions and new lesions, if applicable) and calculated as the percentage of patients with a best overall confirmed response of CR or PR in the brain per modified RECIST 1.1 as assessed by BIRC neuroradiologist. CR: Disappearance of all lesions with lymph nodes measuring \< 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.

GroupValue95% CI
Ceritinib72.749.8 – 89.3
Chemotherapy27.310.7 – 50.2

Adverse events — posted to ClinicalTrials.gov

Time frame: All-cause mortality: from randomization up to approx. 120 months, including post-treatment survival follow-up period. Serious and Other Adverse Events (AEs): from first dose of study treatment until 30 days after last dose (or start of crossover treatment), up to approx. 120 months. For participants who crossed over, AEs were also collected from start of crossover treatment to 30 days post-crossover treatment (extension-treatment period), up to approx. 108 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Ceritinib
Serious: 93/189 (49%)
Deaths: 15/189
Chemotherapy
Serious: 64/175 (37%)
Deaths: 10/187
Chemotherapy to Ceritinib (Extension-treatment)
Serious: 47/100 (47%)
Deaths: 15/100
Ceritinib (Post-treatment Follow-up)
Serious: 0
Deaths: 98/149
Chemotherapy (Post-treatment Follow-up)
Serious: 0
Deaths: 38/60
Chemotherapy to Ceritinib (Post-treatment Follow-up)
Serious: 0
Deaths: 56/83

Serious adverse events (200 terms)

ReactionSystemCeritinibChemotherapyChemotherapy to Ceritinib …Ceritinib (Post-treatment …Chemotherapy (Post-treatme…Chemotherapy to Ceritinib …
PneumoniaInfections and infestations
DyspnoeaRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
Metastases to central nervous systemNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute kidney injuryRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
Pericardial effusionCardiac disorders
DiarrhoeaGastrointestinal disorders
Aspartate aminotransferase increasedInvestigations
SeizureNervous system disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
Alanine aminotransferase increasedInvestigations
Blood creatinine increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
EpilepsyNervous system disorders
HaemoptysisRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Atrial fibrillationCardiac disorders
Myocardial infarctionCardiac disorders
Other adverse events (76 terms — click to expand)

ReactionSystemCeritinibChemotherapyChemotherapy to Ceritinib …Ceritinib (Post-treatment …Chemotherapy (Post-treatme…Chemotherapy to Ceritinib …
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
Gamma-glutamyltransferase increasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Blood alkaline phosphatase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Blood creatinine increasedInvestigations
Weight decreasedInvestigations
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
Back painMusculoskeletal and connective tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
PyrexiaGeneral disorders
NeutropeniaBlood and lymphatic system disorders
Non-cardiac chest painGeneral disorders
ConstipationGastrointestinal disorders
AstheniaGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
DizzinessNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
White blood cell count decreasedInvestigations
Oedema peripheralGeneral disorders
Neutrophil count decreasedInvestigations
Upper respiratory tract infectionInfections and infestations
Amylase increasedInvestigations
Electrocardiogram QT prolongedInvestigations
PruritusSkin and subcutaneous tissue disorders
HyperglycaemiaMetabolism and nutrition disorders
NasopharyngitisInfections and infestations
InsomniaPsychiatric disorders
StomatitisGastrointestinal disorders
DyspepsiaGastrointestinal disorders
InfluenzaInfections and infestations

Most-reported serious reactions: Pneumonia, Dyspnoea, Vomiting, Pleural effusion, Nausea, Pulmonary embolism, Pyrexia, Hyperglycaemia.

Data from ClinicalTrials.gov NCT01828099 adverse events section.

Sponsor's own description

To compare the efficacy and safety of ceritinib with standard first-line chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with stage IIIB (not candidates for definitive multimodality therapy) or stage IV, non-squamous non-small cell lung cancer (NSCLC) harboring a confirmed anaplastic lymphoma kinase (ALK) rearrangement, using the Ventana immunohistochemistry (IHC) test.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study.
    Soria JC, Tan DSW, Chiari R, Wu YL, et al · · 2017 · cited 858× · PMID 28126333 · DOI 10.1016/s0140-6736(17)30123-x
  2. Non-small cell lung cancer in China.
    Chen P, Liu Y, Wen Y, Zhou C. · · 2022 · cited 479× · PMID 36075878 · DOI 10.1002/cac2.12359
  3. ALK inhibitors in non-small cell lung cancer: crizotinib and beyond.
    Awad MM, Shaw AT. · · 2014 · cited 186× · PMID 25322323
  4. Current Landscape of Non-Small Cell Lung Cancer: Epidemiology, Histological Classification, Targeted Therapies, and Immunotherapy.
    Rodak O, Peris-Díaz MD, Olbromski M, Podhorska-Okołów M, et al · · 2021 · cited 159× · PMID 34572931 · DOI 10.3390/cancers13184705
  5. Targeted therapy in cancer.
    Tsimberidou AM. · · 2015 · cited 156× · PMID 26391154 · DOI 10.1007/s00280-015-2861-1
  6. Leptomeningeal disease: current diagnostic and therapeutic strategies.
    Nayar G, Ejikeme T, Chongsathidkiet P, Elsamadicy AA, et al · · 2017 · cited 155× · PMID 29069871 · DOI 10.18632/oncotarget.20272
  7. Management of Brain Metastases in Non-Small-Cell Lung Cancer.
    Ernani V, Stinchcombe TE. · · 2019 · cited 151× · PMID 31715122 · DOI 10.1200/jop.19.00357
  8. Molecular pathways and therapeutic targets in lung cancer.
    Shtivelman E, Hensing T, Simon GR, Dennis PA, et al · · 2014 · cited 150× · PMID 24722523 · DOI 10.18632/oncotarget.1891

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