Phase 3
Completed N=231
LDK378 Versus Chemotherapy in ALK Rearranged (ALK Positive) Patients Previously Treated With Chemotherapy (Platinum Doublet) and Crizotinib
Source: ClinicalTrials.gov NCT01828112 ↗Enrolled (actual)
231
Serious AEs
44.8%
Results posted
Jul 2017
Primary outcomePrimary: Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC) — 5.4; 1.6 months — p=<0.001
◆ Published Evidence
Highly cited
580citations · ~64 / year
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.
Summary
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.
Linked Publications (2)
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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.
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Phase 3 study of ceritinib vs chemotherapy in ALK-rearranged NSCLC patients previously treated with chemotherapy and crizotinib (ASCEND-5): Japanese subset.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression Free Survival (PFS) Per Blinded Independent Review Committee (BIRC) |
5.4; 1.6 | <0.001 sig |
| SECONDARY Overall Survival (OS) |
17.7; 20.1 | — |
| SECONDARY Progression Free Survival (PFS) Per Investigator Assessment |
6.2; 1.6 | — |
| SECONDARY Overall Response Rate (ORR) Per BIRC |
40.9; 6.9 | — |
| SECONDARY Overall Response Rate (ORR) Per Investigator Assessment |
44.3; 6.9 | — |
| SECONDARY Duration of Response (DOR) Per BIRC |
7.6; 10.4 | — |
| SECONDARY Duration of Response (DOR) Per Investigator Assessment |
6.7; 8.3 | — |
| SECONDARY Disease Control Rate (DCR) Per BIRC |
76.5; 37.9 | — |
| SECONDARY Disease Control Rate (DCR) Per Investigator Assessment |
80.0; 39.7 | — |
| SECONDARY Time to Response (TTR) Per BIRC |
6.71; 9.64 | — |
| SECONDARY Time to Response (TTR) Per Investigator Assessment |
6.43; 14.71 | — |
| SECONDARY Overall Intracranial Response Rate (OIRR) Per BIRC |
10.6; 3.0 | — |
| SECONDARY Intracranial Disease Control Rate (IDCR) Per BIRC |
71.2; 53.7 | — |
| SECONDARY Duration of Intracranial Response (DOIR) Per BIRC |
8.3; 16.7 | — |
| SECONDARY Least Squares Mean Scores on the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC-QLQC30) |
62.9; 63.2; 80.5; 75.4; 82.4; 80.7 | — |
| SECONDARY EORTC QLQ-LC13 Time to Definitive Deterioration |
13.4; 2.8 | — |
| SECONDARY Least Squares Mean Scores on the Lung Cancer Symptom Scale (LCSS) |
22.0; 26.3; 28.0; 26.6; 34.6; 39.2 | — |
| SECONDARY Least Squares Mean Scores on the EQ-5D-5L Index |
0.7837; 0.7108 | — |
| SECONDARY Least Squares Mean Scores on the EQ-5D Visual Analogue Scale (VAS) |
71.8; 69.0 | — |
| SECONDARY Cmax for Ceritinib |
90.4; 1170 | — |
| SECONDARY Tmax for Ceritinib |
6.03; 7.15 | — |
| SECONDARY Tlast for Ceritinib |
24; 23.9 | — |
| SECONDARY AUC0-24h for Ceritinib |
1470; 25000 | — |
| SECONDARY Mean Accumulation Ratio (Racc) for Ceritinib |
15.5 | — |
| SECONDARY Clearance Rate at Steady State (CLss/F) for Ceritinib |
30 | — |
| SECONDARY Post-Hoc: All Collected Deaths |
0; 2; 0; 16; 5; 19 | — |
Eligibility Criteria
Inclusion Criteria
- 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.
- 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.
- 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
- Patients must have received previous treatment with crizotinib for the treatment of locally advanced or metastatic NSCLC.
Exclusion Criteria
- Patient with known hypersensitivity to any of the excipients of LDK378 (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon dioxide and magnesium stearate)
- Patient with a history of severe hypersensitivity reaction to pemetrexed or docetaxel or any known excipients of these drugs.
- 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.
Data sourced from ClinicalTrials.gov (NCT01828112) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.