Phase 2
N=138
A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment
Non-Small-Cell Lung Carcinoma
Bottom Line
View on ClinicalTrials.gov: NCT01801111 ↗Enrolled (actual)
138
Serious AEs
28.3%
Results posted
May 2016
Primary outcome: Primary: Recommended Phase 2 Dose (RP2D) of Alectinib
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Erlotinib (Drug); Alectinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Oct 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Recommended Phase 2 Dose (RP2D) of Alectinib |
— | — |
| PRIMARY Percentage of Participants With Dose Limiting Toxicities (DLTs) |
— | — |
| PRIMARY Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Independent Radiological Review Committee (IRC) in Response Evaluable (RE) Population |
50.8 | 0.0005 sig |
| PRIMARY Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants |
44.8 | 0.0599 |
| SECONDARY Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants |
73.1 | — |
| SECONDARY Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population |
51.4 | 0.0001 sig |
| SECONDARY Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants |
50.0 | — |
| SECONDARY Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants |
57.1 | — |
| SECONDARY Duration of Response (DoR) as Assessed by IRC in RE Population |
15.2 | — |
| SECONDARY Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population |
71.0 | — |
| SECONDARY Progression Free Survival (PFS) as Assessed by IRC in Safety Population |
8.9 | — |
| SECONDARY Percentage of Participants Who Died of Any Cause |
54.3 | — |
| SECONDARY Overall Survival (OS) |
29.2 | — |
| SECONDARY Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population |
63.9; 69.6 | — |
| SECONDARY Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1 |
58.8 | — |
| SECONDARY Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria |
44.1 | — |
| SECONDARY CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1 |
11.1 | — |
| SECONDARY CDoR as Assessed by IRC According to RANO Criteria |
7.6 | — |
| SECONDARY Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1 |
18.8 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of Alectinib |
204; 933 | — |
| SECONDARY Time to Cmax (Tmax) of Alectinib |
5.89; 4.12 | — |
| SECONDARY Time to Last Measurable Plasma Concentration (Tlast) of Alectinib |
11.59; 11.65 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib |
1140; 7860 | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib |
1340; 9090 | — |
| SECONDARY Cmax of Alectinib Metabolite |
57.2; 303 | — |
| SECONDARY Tmax of Alectinib Metabolite |
8.03; 7.00 | — |
| SECONDARY Tlast of Alectinib Metabolite |
11.59; 11.65 | — |
| SECONDARY AUC(0-10) of Alectinib Metabolite |
300; 2590 | — |
| SECONDARY AUC(0-last) of Alectinib Metabolite |
378; 3040 | — |
| SECONDARY Metabolite to Parent Ratio Based on AUC(0-10) |
0.278; 0.349 | — |
| SECONDARY Metabolite to Parent Ratio Based on AUC(0-last) |
0.298; 0.354 | — |
| SECONDARY Trough Plasma Concentration (Ctrough) of Alectinib |
761 | — |
| SECONDARY Ctrough of Alectinib Metabolite |
244 | — |
| SECONDARY Peak to Trough Ratio of Alectinib |
1.23 | — |
| SECONDARY Accumulation Ratio of Alectinib |
6.95 | — |
| SECONDARY Accumulation Ratio of Alectinib Metabolite |
8.68 | — |
Summary
This open-label, non-randomized, multicenter, Phase 1/2 study will evaluate the safety and efficacy of alectinib in participants with non-small cell lung cancer who have ALK mutation and failed crizotinib treatment. In Part 1, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Part 2, participants will receive the recommended phase 2 dose (RP2D) of alectinib as determined in Part 1. Treatment will continue in Part 1 and Part 2 on the same dose until disease progression. In Part 3, following disease progression, participants without epidermal growth factor receptor (EGFR) mutation will be offered continued treatment with alectinib, participants with EGFR mutations will be offered a combination of alectinib and erlotinib.
Eligibility Criteria
Inclusion Criteria
- Locally advanced or metastatic non-small cell lung cancer (stage IIIB or IV by American Joint Committee on Cancer [AJCC])
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Documented ALK rearrangement based on Food and Drug Administration (FDA)-approved test
- Prior treatment with crizotinib and progression according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1) criteria. Participants had to have a minimum 1-week wash-out period between the last dose of crizotinib and the first dose of study treatment. Participants can either be chemotherapy-naïve or have received at least one line of platinum-based chemotherapy
- Adequate hematologic, hepatic, and renal function
- Participants with brain or leptomeningeal metastases are allowed if protocol defined criteria are met
- Measurable disease according to RECIST v1.1 prior to administration of first dose of study drug
Exclusion Criteria
- Receipt of any other ALK inhibitors in addition to crizotinib
- Receipt of any prior cytotoxic chemotherapy for ALK-positive NSCLC within 4 weeks prior to the first dose of study drug
- Participants who received crizotinib or any other tyrosine kinase inhibitors need to have a minimum 1-week washout period before the first dose of study drug
- Active or uncontrolled infectious diseases requiring treatment
- National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03) Grade 3 or higher toxicities due to prior therapy that have not shown improvement and are considered to interfere with current study medication
- History of organ transplant
- Co-administration of anti-cancer therapies other than those administered in this study
- Baseline corrected Q-T interval (QTc) greater than (>) 470 milliseconds, or baseline symptomatic bradycardia (less than 45 heart beats per minute)
- Pregnant or breastfeeding women
- Known Human Immunodeficiency Virus (HIV) positivity or Acquired Immunodeficiency Syndrome (AIDS)-related illness
- History of hypersensitivity to any of the additives in the alectinib formulation
- Any clinically significant concomitant disease or condition that could interfere with, or for which treatment might interfere with, the conduct of the study, or absorption of oral medications, or that would, in the opinion of the principal investigator, pose an unacceptable risk to the participant in the study
Data sourced from ClinicalTrials.gov (NCT01801111). 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.