LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib

A Phase III, Multicenter, Randomized, Open-label Study of Oral LDK378 Versus Standard Chemotherapy in Adult Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer Who Have Been Treated Previously With Chemotherapy (Platinum Doublet) and Crizotinib

The primary purpose of the study was to compare the antitumor activity of LDK378 vs. chemotherapy in patients previously treated with chemotherapy (platinum doublet) and crizotinib. Patients in the chemotherapy arm were given the option to switch to LDK378 after confirmed progressive disease (PD), while also had the choice to continue with pemetrexed treatment.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Ceritinib; Drug: Pemetrexed; Drug: Docetaxel

Detailed Description

A total of 231 patients were randomized to one of the two treatment arms in a 1:1 ratio. Randomization was stratified by World Health Organization (WHO) performance status (0 versus 1-2) and whether the patient had brain metastases at screening. The study was planned to be ended once the final overall survival (OS) analysis was performed (at the earliest of approximately 196 deaths observed or statistical significance reached at earlier OS interim analysis).

Following an agreement between Novartis and European Medicines Agency (EMA) in May 2023 to terminate the trial earlier, this study was completed when the total number of deaths was 190. Patients who had Response Evaluation Criteria In Solid Tumors (RECIST)-defined disease progression as confirmed by the Blinded Independent Review Committee (BIRC), but who, in the opinion of the Investigator, had continued clinical benefit from study treatment on either the chemotherapy arm or the ceritinib arm, continued to receive treatment. These patients continued assessments in the treatment phase. In addition, only patients randomized to the chemotherapy arm were allowed to crossover to receive ceritinib therapy (extension treatment [ET] phase) after BIRC-confirmed, RECIST-defined disease progression, and provided they met the eligibility requirements.

• Study Type: Interventional
• Enrollment (Actual): 231
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1000
    • Novartis Investigative Site
  • Edegem, Belgium, 2650
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Novartis Investigative Site
• France
  • Besancon cedex, France, 25030
    • Novartis Investigative Site
  • Brest, France, 29609
    • Novartis Investigative Site
  • Caen, France, 14021
    • Novartis Investigative Site
  • Le Mans, France, 72000
    • Novartis Investigative Site
  • Mulhouse cedex, France, 68070
    • Novartis Investigative Site
  • Paris, France, 75970
    • Novartis Investigative Site
  • Strasbourg, France, F 67085
    • Novartis Investigative Site
  • Suresnes, France, 92150
    • Novartis Investigative Site
  • Bouches Du Rhone
    • Marseille cedex 20, Bouches Du Rhone, France, 13915
      • Novartis Investigative Site
• Germany
  • Bad Berka, Germany, 99438
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Esslingen, Germany, 73730
    • Novartis Investigative Site
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Koeln, Germany, 51109
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
• Hong Kong
  • Hong Kong, Hong Kong
    • Novartis Investigative Site
  • Pokfulam, Hong Kong
    • Novartis Investigative Site
• Ireland
  • Dublin 4, Ireland, DO4
    • Novartis Investigative Site
  • Co Limerick
    • Limerick, Co Limerick, Ireland, V94 YX29
      • Novartis Investigative Site
• Israel
  • Kfar Saba, Israel, 44281
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
• Italy
  • AV
    • Avellino, AV, Italy, 83100
      • Novartis Investigative Site
  • MB
    • Monza, MB, Italy, 20900
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
  • PG
    • Perugia, PG, Italy, 06129
      • Novartis Investigative Site
  • PI
    • Pisa, PI, Italy, 56124
      • Novartis Investigative Site
  • PN
    • Aviano, PN, Italy, 33081
      • Novartis Investigative Site
  • RE
    • Reggio Emilia, RE, Italy, 42123
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00189
      • Novartis Investigative Site
  • TO
    • Orbassano, TO, Italy, 10043
      • Novartis Investigative Site
  • VR
    • Verona, VR, Italy, 37126
      • Novartis Investigative Site
• Japan
  • Niigata, Japan, 951 8520
    • Novartis Investigative Site
  • Aichi
    • Nagoya, Aichi, Japan, 464 8681
      • Novartis Investigative Site
  • Chiba
    • Kashiwa, Chiba, Japan, 277 8577
      • Novartis Investigative Site
  • Fukuoka
    • Fukuoka city, Fukuoka, Japan, 812-8582
      • Novartis Investigative Site
    • Fukuoka-city, Fukuoka, Japan, 811-1395
      • Novartis Investigative Site
  • Hyogo
    • Akashi, Hyogo, Japan, 673-8558
      • Novartis Investigative Site
  • Okayama
    • Okayama-city, Okayama, Japan, 700-8558
      • Novartis Investigative Site
  • Osaka
    • Hirakata-city, Osaka, Japan, 573-1191
      • Novartis Investigative Site
    • Osaka Sayama, Osaka, Japan, 589 8511
      • Novartis Investigative Site
    • Osaka-city, Osaka, Japan, 541-8567
      • Novartis Investigative Site
    • Takatsuki, Osaka, Japan, 569-8686
      • Novartis Investigative Site
  • Tokyo
    • Koto ku, Tokyo, Japan, 135 8550
      • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 06351
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 03722
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 05505
    • Novartis Investigative Site
  • Seocho Gu
    • Seoul, Seocho Gu, Korea, Republic of, 06591
      • Novartis Investigative Site
• Lebanon
  • Ashrafieh, Lebanon, 166830
    • Novartis Investigative Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Novartis Investigative Site
• Portugal
  • Lisboa, Portugal, 1649 035
    • Novartis Investigative Site
• Russian Federation
  • Moscow, Russian Federation, 115478
    • Novartis Investigative Site
  • Moscow Region Istra Village, Russian Federation, 143423
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 197022
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
  • Singapore, Singapore, 168583
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28041
    • Novartis Investigative Site
  • Madrid, Spain, 28034
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Andalucia
    • Sevilla, Andalucia, Spain, 41013
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08028
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Galicia
    • La Coruna, Galicia, Spain, 15006
      • Novartis Investigative Site
    • Santiago De Compostela, Galicia, Spain, 15706
      • Novartis Investigative Site
• Switzerland
  • Luzern, Switzerland, 6000
    • Novartis Investigative Site
  • St Gallen, Switzerland, 9007
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06230
    • Novartis Investigative Site
  • Pendik Istanbul, Turkey, 34899
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Novartis Investigative Site
  • London, United Kingdom, SE1 9RT
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO30 3JB
    • Novartis Investigative Site
  • Gloucestershire
    • Cheltenham, Gloucestershire, United Kingdom, GL53 7AN
      • Novartis Investigative Site
  • Grampian Region
    • Aberdeen, Grampian Region, United Kingdom, AB25 2ZN
      • Novartis Investigative Site
• United States
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Cancer Institute
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists of North Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Marywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Iowa
    • Iowa, Iowa, United States, 52242
      • Uni Of Iowa Hospitals And Clinics
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Oklahoma Cancer Specialists and Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology-Sugarland
    • Waco, Texas, United States, 76712
      • Texas Oncology Cancer Care and Research Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is anaplastic lymphoma kinase (ALK) positive as assessed by the FDA approved Abbott FISH Test.
2. Patient has stage IIIB or IV diagnosis and must have received one or two prior regimens (including platinum- doublet) of cytotoxic chemotherapy for the treatment of locally advanced or metastatic NSCLC.
3. Patient has at least one measurable lesion as defined by RECIST 1.1. A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation
4. Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.

Exclusion Criteria:

1. Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
2. Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs.
3. Patient with symptomatic central nervous system (CNS) metastases who is neurologically unstable or has required increasing doses of steroids within the 2 weeks prior to screening to manage CNS symptoms.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceritinib; Ceritinib 750 mg	Drug: Ceritinib; Ceritinib was the investigational treatment and was provided as 150 mg hard gelatin capsules for oral use. The dose was 750 mg once daily.
Active Comparator: Chemotherapy; Chemotherapy as determined by BIRC	Drug: Pemetrexed; Pemetrexed was one of the chemotherapy treatments. Pemetrexed, a reconstituted solution, was intravenously administered over 10 minutes at 500 mg/m^2 every 21 days.; Drug: Docetaxel; Docetaxel was one of the chemotherapy treatments. Docetaxel, a reconstituted solution, was intravenously administered over 1 hour, at 75 mg/m^2 every 21 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC)	PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.	From the date of randomization to the date of first radiologically documented disease progression or death due to any cause up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as time from date of randomization to date of death due to any cause.	Up to approximately 114 months
Progression Free Survival (PFS) Per Investigator Assessment	PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.	Up to approximately 84 months
Overall Response Rate (ORR) Per BIRC	ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR): (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST), v. 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.	Up to approximately 54 months
Overall Response Rate (ORR) Per Investigator Assessment	ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR): (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST), v. 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.	Up to approximately 93 months
Duration of Response (DOR) Per BIRC	DOR defined as the time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer. 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.	Up to approximately 54 months
Duration of Response (DOR) Per Investigator Assessment	DOR defined as the time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer. 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.	Up to approximately 93 months
Disease Control Rate (DCR) Per BIRC	DCR was defined as the percentage of participants with best overall response of CR, PR, or stable disease (SD). 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.	Up to approximately 54 months
Disease Control Rate (DCR) Per Investigator Assessment	DCR was defined as the percentage of participants with best overall response of CR, PR, or stable disease (SD). 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.	Up to approximately 93 months
Time to Response (TTR) Per BIRC	TTR was defined as the time from date of randomization to date of first documented response (CR or PR). 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.	Up to approximately 52 weeks
Time to Response (TTR) Per Investigator Assessment	TTR was defined as the time from date of randomization to date of first documented response (CR or PR). 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.	Up to approximately 45 weeks
Overall Intracranial Response Rate (OIRR) Per BIRC	OIRR was defined as the ORR based on lesions in brain (target, nontarget 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.	Up to approximately 18 months
Intracranial Disease Control Rate (IDCR) Per BIRC	IDCR was defined as the DCR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated as the proportion of patients with a best overall response of CR or PR or SD (or non-CR/nonPD) in the brain per modified RECIST 1.1 as assessed by BIRC neuro-radiologist. 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.	Up to approximately 18 months
Duration of Intracranial Response (DOIR) Per BIRC	DOIR was defined as the DOR based on lesions in brain (target, non-target lesions (and new lesions, if applicable) and calculated from the time of first documented response of CR or PR to the date of the first documented disease progression in the brain or death due to any cause per modified RECIST 1.1 as assessed by BIRC neuro-radiologist. 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.	Up to approximately 18 months
Least Squares Mean Scores on the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC-QLQC30)	The EORTC QLQ-C30 questionnaire contained 30 items and was composed of both multi-item scales and single item measures. These included five functional scales (physical, role, emotional, cognitive, and social functioning), three symptom scales (fatigue, nausea/vomiting, and pain), six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial impact), and a global health status/quality of life (QoL) scale. All of the scales and single items ranged from 0 to 100. A high scale score represented a higher response level. Thus, a high score for a functional scale indicated a high/healthy level of functioning, a high score for the QoL indicated high QoL, but a high score for a symptom scale/single item indicated a high level of symptomatology/problems. Data from all collected time points were combined and presented using a repeated measures model for longitudinal data.	Screening and treatment phase up to 92 months
EORTC QLQ-LC13 Time to Definitive Deterioration	The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) was used in conjunction with the EORTC QLQ-C30 and provided information on an additional 13 items specifically related to lung cancer. The lung cancer module incorporated one multi-item scale to assess dyspnea, and 9 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the domain scores ranged from 0 to 100. A high score indicated a high level of symptoms. QLQ-LC13 time to definitive deterioration was defined as the time from randomization to the earliest date a patient shows a 10 point or higher increase from baseline in any of the ALCLC13 scores related to pain in chest, cough, or dyspnea (with no later change below this threshold), or death due to any cause. Each cycle was 21 days.	Screening and treatment phase up to 92 months
Least Squares Mean Scores on the Lung Cancer Symptom Scale (LCSS)	The LCSS patient scale uses a 24-hour recall period and contains nine items: six measuring major symptoms for lung cancer (appetite loss, fatigue, cough, dyspnea, hemoptysis, pain), and three summary items related to total symptom distress, normal activity status, and overall quality of life. The total scale used is a 100 mm visual analog scale to measure the intensity of patient responses, with zero corresponding to the lowest rating (best status) and 100 representing the highest rating (worst status). The total score was calculated as the mean of the 9 items. Data from all collected time points were combined and presented using a repeated measures model for longitudinal data.	Screening and treatment phase up to 92 months
Least Squares Mean Scores on the EQ-5D-5L Index	The EQ-5D descriptive classification consists of five dimensions of health: mobility, self-care, usual activities, anxiety/depression and pain/discomfort. Patients are requested to select the statement which best describes their condition on that day for each dimension. EQ-5D-5L index scores can range from -0.59 to 1, where 1 is the best possible health state. Data from all collected time points were combined and presented using a repeated measures model for longitudinal data.	Screening and treatment phase up to 92 months
Least Squares Mean Scores on the EQ-5D Visual Analogue Scale (VAS)	The EQ-5D descriptive classification consists of five dimensions of health: mobility, self-care, usual activities, anxiety/depression and pain/discomfort. Patients are requested to select the statement which best describes their condition on that day for each dimension. EQ VAS scores can range from 0 to 100, where 100 is the best possible health state. Data from all collected time points were combined and presented using a repeated measures model for longitudinal data.	Screening and treatment phase up to 92 months
Cmax for Ceritinib	The observed maximum plasma concentration following administration	Cycle 1, Day 1 and Cycle 2, Day 1: pre-dose and 1, 2, 4, 6, 8, and 24 hours post-dose. Each cycle was 21 days.
Tmax for Ceritinib	The time to reach peak or maximum concentration	Cycle 1, Day 1 and Cycle 2, Day 1: pre-dose and 1, 2, 4, 6, 8, and 24 hours post-dose. Each cycle was 21 days.
Tlast for Ceritinib	The time to last quantifiable concentration	Cycle 1, Day 1 and Cycle 2, Day 1: pre-dose and 1, 2, 4, 6, 8, and 24 hours post-dose. Each cycle was 21 days.
AUC0-24h for Ceritinib	The area under the plasma concentration-time curve calculated from time zero to 24 hours	Cycle 1, Day 1 and Cycle 2, Day 1: pre-dose and 1, 2, 4, 6, 8, and 24 hours post-dose. Each cycle was 21 days.
Mean Accumulation Ratio (Racc) for Ceritinib	Accumulation ratio calculated using AUC0-24 values obtained from a dosing interval at steady-state (Cycle 2, Day 1) divided by AUC0-24 on Cycle 1, Day 1.	Cycle 1, Day 1 and Cycle 2, Day 1: pre-dose and 1, 2, 4, 6, 8, and 24 hours post-dose. Each cycle was 21 days.
Clearance Rate at Steady State (CLss/F) for Ceritinib	The apparent total body clearance from plasma. CLss/F is calculated from AUC0-24 assuming steady state (CLss/F=Dose/AUC0-24).	Cycle 1, Day 1 and Cycle 2, Day 1: pre-dose and 1, 2, 4, 6, 8, and 24 hours post-dose. Each cycle was 21 days.
Post-Hoc: All Collected Deaths	Pre-treatment deaths: from day of patient's informed consent to the day before first dose of study treatment. On-treatment deaths: from first dose of study treatment to 30 days following the last dose of study treatment at the end of treatment phase. For crossover patients, from first dose of ceritinib at the extension treatment phase to 30 days following the last dose. Survival Follow-up deaths: from Day 31 after last dose of study treatment to the data cut-off date.	Pre-treatment and on-treatment deaths: Up to approximately 8 years. Post-treatment survival follow-up deaths: Up to an additional 2.5 years.

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Kiura K, Imamura F, Kagamu H, Matsumoto S, Hida T, Nakagawa K, Satouchi M, Okamoto I, Takenoyama M, Fujisaka Y, Kurata T, Ito M, Tokushige K, Hatano B, Nishio M. Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset. Jpn J Clin Oncol. 2018 Apr 1;48(4):367-375. doi: 10.1093/jjco/hyy016.
• Shaw AT, Kim TM, Crino L, Gridelli C, Kiura K, Liu G, Novello S, Bearz A, Gautschi O, Mok T, Nishio M, Scagliotti G, Spigel DR, Deudon S, Zheng C, Pantano S, Urban P, Massacesi C, Viraswami-Appanna K, Felip E. Ceritinib versus chemotherapy in patients with ALK-rearranged non-small-cell lung cancer previously given chemotherapy and crizotinib (ASCEND-5): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2017 Jul;18(7):874-886. doi: 10.1016/S1470-2045(17)30339-X. Epub 2017 Jun 9.

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2013
• Primary Completion (Actual): January 26, 2016
• Study Completion (Actual): November 10, 2023

Study Registration Dates

• First Submitted: April 2, 2013
• First Submitted That Met QC Criteria: April 9, 2013
• First Posted (Estimated): April 10, 2013

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 16, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy; NSCLC; Non-Small Cell Lung Cancer; lung cancer; lung adenocarcinoma; Non small cell lung cancer; Non-small cell lung carcinoma (NSCLC); treatment of lung cancer after first metastasis; Non small cell lung carcinoma; ALK; crizotinib; LDK378; ALK-positive; ALK-rearranged advanced non-small cell lung cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors; Protein Kinase Inhibitors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Pemetrexed; Ceritinib
• Other Study ID Numbers: CLDK378A2303; 2012-005637-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No