Phase 3
N=119
Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase (ALK)-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) Participants Previously Treated With Platinum-Based Chemotherapy and Crizotinib
Non-small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02604342 ↗Enrolled (actual)
119
Serious AEs
23.7%
Results posted
Feb 2018
Primary outcome: Primary: Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator — 10.9; 1.4 months — p=<0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Alectinib (Drug); Docetaxel (Drug); Pemetrexed (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Jan 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator |
10.9; 1.4 | <0.001 sig |
| SECONDARY Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC |
66.7; 0.0 | <0.001 sig |
| SECONDARY PFS Using RECIST Version 1.1 as Assessed by IRC |
7.1; 1.6 | — |
| SECONDARY Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC |
50.6; 2.5; 36.1; 11.4 | — |
| SECONDARY Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC |
86.1; 25.0; 76.4; 48.6 | — |
| SECONDARY Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC |
12.0; 2.7; 9.7; NA | — |
| SECONDARY PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC |
9.7; 1.4; 8.1; 1.5 | — |
| SECONDARY Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC |
NA; 1.6 | — |
| SECONDARY Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC |
82.7; 25.0 | — |
| SECONDARY Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC |
48.1; 0.0 | — |
| SECONDARY Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC |
13.9; NA | — |
| SECONDARY Overall Survival (OS) |
27.8; NA | — |
| SECONDARY Plasma Concentration of Alectinib |
559 | — |
| SECONDARY Plasma Concentration of Alectinib Metabolite |
240 | — |
| SECONDARY Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time |
92.4; 85.0; 96.1; 83.3; 97.2; 60.0 | — |
| SECONDARY Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time |
92.4; 82.5; 96.1; 83.3; 97.2; 63.3 | — |
| SECONDARY Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time |
88.9; 82.9; 86.6; 78.8; 91.9; 58.6 | — |
| SECONDARY Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population |
18.1; 16.6; 4.1; 3.3; NA; NA | — |
| SECONDARY Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population |
NA; 16.6; 9.7; 1.4; NA; NA | — |
| SECONDARY Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population |
13.3; 8.3; 5.6; 1.2 | — |
| SECONDARY Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population |
16.6; 8.3; 14.4; 1.0 | — |
| SECONDARY TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population |
2.8; 1.4 | — |
| SECONDARY TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population |
1.4; 1.4 | — |
| SECONDARY Percentage of Participants With Adverse Events (AEs) |
89.6; 89.2 | — |
Summary
This randomized active-controlled multicenter Phase III open-label study will evaluate and compare between treatment groups the efficacy of alectinib versus chemotherapy in participants with ALK-positive advanced NSCLC who were previously treated with chemotherapy and crizotinib, as measured by investigator-assessed progression-free survival (PFS) and to evaluate and compare between treatment groups the central nervous system (CNS) objective response rate (C-ORR) in participants with measurable CNS metastases at baseline, as assessed by an Independent Review Committee (IRC).
Eligibility Criteria
Inclusion Criteria
- Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC that is ALK-positive. ALK positivity must have been determined by a validated fluorescence in situ hybridization (FISH) test (recommended probe, Vysis ALK Break-Apart Probe) or a validated immunohistochemistry (IHC) test (recommended antibody, clone D5F3)
- Participant had received two prior systemic lines of therapy, which must have included one line of platinum-based chemotherapy and one line of crizotinib
- Prior CNS or leptomeningeal metastases allowed if asymptomatic
- Participants with symptomatic CNS metastases for whom radiotherapy is not an option will be allowed to participate in this study
- Measurable disease by RECIST Version 1.1 prior to the administration of study treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- For all females of childbearing potential, a negative pregnancy test must be obtained within 3 days before starting study treatment
Exclusion Criteria
- Participants with a previous malignancy within the past 3 years are excluded (other than curatively treated basal cell carcinoma of the skin, early gastrointestinal [GI] cancer by endoscopic resection or in situ carcinoma of the cervix)
- Participants who have received any previous ALK inhibitor other than crizotinib
- Any GI disorder that may affect absorption of oral medications
Data sourced from ClinicalTrials.gov (NCT02604342). 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.