Phase 3
N=303
A Study Comparing Alectinib With Crizotinib in Treatment-Naive Anaplastic Lymphoma Kinase-Positive Advanced Non-Small Cell Lung Cancer Participants
Non-Small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT02075840 ↗Enrolled (actual)
303
Serious AEs
38.9%
Results posted
Mar 2018
Primary outcome: Primary: Progression-Free Survival (PFS) by Investigator Assessment — NA; 11.1 months — p=<0.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Alectinib (Drug); Crizotinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Feb 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-Free Survival (PFS) by Investigator Assessment |
NA; 11.1 | <0.0001 sig |
| PRIMARY Percentage of Participants With PFS Event by Investigator Assessment |
40.8; 67.5 | — |
| SECONDARY PFS Independent Review Committee (IRC)-Assessed |
25.7; 10.4 | <0.0001 sig |
| SECONDARY Percentage of Participants With PFS Event by IRC |
41.4; 60.9 | — |
| SECONDARY Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using RECIST V1.1 Criteria |
11.8; 45.0 | <0.0001 sig |
| SECONDARY Percentage of Participants With Central Nervous System (CNS) Progression as Determined by IRC Using Revised Assessment in Neuro Oncology (RANO) Criteria |
10.5; 35.8 | — |
| SECONDARY Percentage of Participants With Objective Response Rate (ORR) of Complete Response (CR) or Partial Response (PR) as Determined by The Investigators According to RECIST V1.1 Criteria |
82.9; 75.5 | 0.0936 |
| SECONDARY Duration of Response (DOR) According to RECIST V1.1 Criteria as Assessed by the Investigators |
42.3; 11.1 | — |
| SECONDARY Overall Survival (OS) |
81.1; 54.2 | 0.1320 |
| SECONDARY Percentage of Participants With OS Event |
50.0; 48.3 | — |
| SECONDARY Percentage of Participants With CNS ORR of CR or PR IRC-assessed According to RECIST v1.1 Criteria |
81.0; 50.0; 59.4; 25.9 | — |
| SECONDARY CNS DOR IRC-assessed According to RECIST v1.1 Criteria |
17.3; 5.5 | — |
| SECONDARY Percentage of Participants With Adverse Events |
96.7; 98.0 | — |
| SECONDARY Area Under The Concentration-Time Curve (AUC) of Alectinib |
713; 5030 | — |
| SECONDARY Maximum Concentration (Cmax) of Alectinib |
211; 717 | — |
| SECONDARY Time to Reach Cmax (Tmax) of Alectinib |
6.03; 4.02 | — |
| SECONDARY AUC of Alectinib Metabolite |
142; 2230 | — |
| SECONDARY Cmax of Alectinib Metabolite |
56.2; 321 | — |
| SECONDARY Tmax of Alectinib Metabolite |
8.00; 6.00 | — |
| SECONDARY Time to Deterioration by European Organization for The Research And Treatment of Cancer (EORTC) Quality Of Life Questionnaire Core 30 (C30) |
NA; NA; NA; NA | 0.2079 |
| SECONDARY Percentage of Participants With Deterioration by EORTC Quality Of Life Questionnaire Core 30 (C30) |
21.7; 25.2; 17.1; 9.9 | — |
| SECONDARY Time to Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) |
NA; NA; 22.8; NA; NA; NA | 0.7042 |
| SECONDARY Percentage of Participants With Deterioration by EORTC Quality of Life Questionnaire Lung Cancer Module 13 (LC13) |
11; 11; 28; 16; 18; 12 | — |
| SECONDARY Health-Related Quality of Life (HRQoL) by EORTC Quality of Life Questionnaire C30 Score |
66.67; 66.67; 66.67; 66.67; 75.0; 75.0 | — |
| SECONDARY HRQoL by EORTC Quality of Life Questionnaire LC13 Score Coughing |
33.33; 33.33; 33.33; 33.33; 33.33; 33.33 | — |
| SECONDARY HRQoL by EORTC Quality of Life Questionnaire LC13 Score Dyspnoea |
22.22; 22.22; 22.22; 22.22; 22.22; 11.11 | — |
| SECONDARY HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Chest |
33.33; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
| SECONDARY HRQoL by EORTC Quality of Life Questionnaire LC13 Score Pain in Arm and Shoulder |
0.0; 0.0; 0.0; 0.0; 0.0; 0.0 | — |
Summary
This randomized, active controlled, multicenter phase III open-label study is designed to evaluate the efficacy and safety of alectinib compared with crizotinib treatment in participants with treatment-naive anaplastic lymphoma kinase-positive (ALK-positive) advanced non-small cell lung cancer (NSCLC). Participants will be randomized in a 1:1 ratio to receive either alectinib, 600 milligrams (mg) orally twice daily (BID), or crizotinib, 250 mg orally BID. Participants will receive treatment until disease progression, unacceptable toxicity, withdrawal of consent, or death. The study is expected to last approximately 144 months.
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 as assessed by the Ventana immunohistochemistry (IHC) test
- Life expectancy of at least 12 weeks
- Eastern cooperative oncology group performance status (ECOG PS) of 0-2
- Participants with no prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC
- Adequate renal, and hematologic function
- Participants must have recovered from effects of any major surgery or significant traumatic injury at least 28 days before the first dose of study treatment
- Measurable disease by response evaluation criteria in solid tumors (RECIST) version 1.1 (v1.1) prior to the administration of study treatment
- Prior brain or leptomeningeal metastases allowed if asymptomatic (e.g., diagnosed incidentally at study baseline)
- Negative pregnancy test for all females of child bearing potential
- Use of highly effective contraception as defined by the study protocol
Exclusion Criteria
- Participants with a previous malignancy within the past 3 years
- Any gastrointestinal (GI) disorder or liver disease
- National cancer institute common terminology criteria for adverse events (NCI CTCAE) (version 4.0) Grade 3 or higher toxicities due to any prior therapy (e.g., radiotherapy) (excluding alopecia)
- History of organ transplant
- Co-administration of anti-cancer therapies other than those administered in this study
- Participants with baseline QTc greater than (>) 470 milliseconds or symptomatic bradycardia
- Recipient of strong/potent cytochrome P4503A inhibitors or inducers within 14 days prior to the first dose until the end of study treatment
- Recipient of any drug with potential QT interval prolonging effects within 14 days prior to the first dose for all participants and while on treatment through the end of the study for crizotinib-treated participants only
- History of hypersensitivity to any of the additives in the alectinib and crizotinib drug formulation
- Pregnancy or lactation
- Any clinically significant disease or condition (or history of) that could interfere with, or for which the treatment might interfere with, the conduct of the study or the absorption of oral medications or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in this study
- Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the participant before trial entry
Data sourced from ClinicalTrials.gov (NCT02075840). 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.