An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) Gene

The objective response rate (ORR) as a measure of anti-tumor efficacy of oral PF-02341066 in participants with advanced NSCLC with an ALK gene translocation or inversion after failure of at least one line of chemotherapy.

Time frame: 6 years

Population: Response-evaluable populations: defined as participants in either the SA-ALK positive by IUO population or SA-ALK positive by non-IUO population, respectively, who had adequate baseline tumor assessment.

Incidence of adverse events and laboratory abnormalities (severity graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], version 4.0).

Time frame: 6 years

Population: The safety analysis population included all participants who were enrolled and received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing).

DCR at 6 and 12 weeks was defined as the percentage of participants with a confirmed CR, confirmed PR, or SD (according to RECIST v 1.1) at 6 weeks and 12 weeks, respectively.

Time frame: 6 years

Population: Response-evaluable populations: defined as participants in either the SA-ALK positive by IUO population or SA-ALK positive by non-IUO population, respectively, who had adequate baseline tumor assessment.

DR was defined as the time from the first documentation of objective tumor response (CR or PR) that was subsequently confirmed, to the first documentation of objective tumor progression or to death on study due to any cause, whichever occurred first. DR (in months) was calculated as (first date of PD or death - first date of CR or PR that was subsequently confirmed + 1)/30.4.

Time frame: 6 years

Population: Response-evaluable populations: defined as participants in either the SA-ALK positive by IUO population or SA-ALK positive by non-IUO population, respectively, who had adequate baseline tumor assessment.

The frequency of the candidate gene alleles, HLA-DQA1\*02:01, HLA-DQB1\*02:02, HLA-DRB1\*07:01 and TNXB/rs12153855, were measured in alanine transaminase (ALT) Cases and ALT Controls to evaluate if there were statistically significant associations that would support or suggest any predictive (ie, diagnostic) value of these markers in identifying participants who were at increased risk for hepatic toxicity. The frequency of 2 additional HLA gene alleles, HLA-B\*57:01 and HLA-DRB1\*15:01, were also measured in ALT Cases and ALT Controls. ALT Cases are defined as those patients with a baseline ALT of ≤1xULN and at least one on-treatment ALT assessment of \>3x upper limit of normal (ULN), and ALT Controls represent those patients with baseline and on-treatment assessments of ALT of ≤1xULN.

Time frame: 6 years

Population: The All Genotyped Population was defined as all participants in the safety analysis population who had at least 1 genotype result. The Pharmacogenomic Evaluable (PE) Population was defined as participants in the All Genotyped Population who had an HLA genotype result and were designated as an ALT Case or Control.

The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), global health status/quality of life, disease/treatment related symptoms (fatigue, pain, nausea/vomiting, dyspnea, appetite loss, sleep disturbance, constipation, and diarrhoea), and the perceived financial impact of disease. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-C30 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher (worse) symptom severity, higher (better) functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

Time frame: 6 years

Population: The patient reported outcomes (PRO) evaluable population was defined as the participants from the safety analysis (SA) population who completed a baseline assessment and at least one post-baseline assessment.

The EORTC QLQ-C30 consists of 30 questions which assess five functional domains (physical, role, cognitive, emotional, and social), global health status/quality of life, disease/treatment related symptoms (fatigue, pain, nausea/vomiting, dyspnoea, appetite loss, sleep disturbance, constipation, and diarrhoea), and the perceived financial impact of disease. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-C30 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher (worse) symptom severity, higher (better) functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

Time frame: 6 years

Population: The PRO evaluable population was defined as the participants from the SA population who completed a baseline assessment and at least one post-baseline assessment.

The QLQ-LC13 consists of 1 multi-item scale and 9 single items that assess specific symptoms (dyspnoea, cough, hemoptysis, and site-specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer patients. n is the number of participants who completed the scale at baseline and at the respective Cycle. The subscales of the EORTC QLQ-LC13 were scored based on the EORTC scoring manual. The transformed scores range from 0-100. Higher scores indicate higher (worse) symptom severity, higher (better) functioning, and better global QoL. Negative change from Baseline scores indicate an improvement in symptoms, decreased functioning, or decreased QoL, while positive change scores indicate an increase in functioning, increased QoL, or deterioration in symptoms.

Time frame: 6 years

Population: The PRO evaluable population was defined as the participants from the SA population who completed a baseline assessment and at least one post-baseline assessment.

Molecular profiling outcomes included:Types of EML4-ALK fusion variants and ALK protein expression; Although a secondary objective was defined to explore the relationship of ALK gene fusion to the presence of ALK protein and fusion transcript, no additional analyses of ALK fusion variants or ALK protein were performed for technical reasons. Analyses of change from Baseline in the expression of biomarkers relevant to signaling pathways were not performed because paired Baseline and on-treatment (Cycle 2) tumor tissue required for the analysis, which were to be collected on an optional basis, were not available.

Time frame: 6 years

Population: The safety analysis population included all participants who received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing) and were ALK positive by IUO (SA-ALK positive by IUO population)

OS was defined as the time from the Cycle 1 Day 1 dose to the date of death due to any cause. OS (in months) was calculated as (date of death - date of Cycle 1 Day 1 dose + 1)/30.4.

Time frame: 6 years

Population: The safety analysis populations included all participants who received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing), and were ALK positive either by IUO (SA-ALK positive by IUO population) or by non-IUO (SA-ALK positive by non-IUO population), respectively.

The EQ-5D descriptive system measured a patient's health state on 5 dimensions which included: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The respondent's self-rated health was assessed on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state) by the EQ-VAS. n is the number of participants who completed the scale at baseline and at the respective Cycle.

Time frame: 6 years

Population: The PRO evaluable population was defined as the participants from the SA population who completed a baseline assessment and at least one post-baseline assessment.

The participants who responded to the question: Have you experienced any visual disturbances? Only the participants who answered yes were instructed to complete the rest of the questionnaire. N was the number of participants who had completed the first question.

Time frame: 6 years

Population: The safety analysis population included all participants who were enrolled and received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing).

Plasma concentrations of crizotinib (PF-02341066) and its metabolite PF-06260182. The method of dispersion is % coefficient of variation.

Time frame: 6 years

Population: All participants who have ≥ 1 measurement of PF-02341066 or PF-06260182 at the time of reporting are included in PK analysis. Concentration at Cycle 2 Day 1 and beyond are considered steady state, and only included those who received at least 14 continuous days of 250 mg BID dosing.

Six-month and 1-year survival probabilities were defined as the probabilities of survival at 6 months and 1 year, respectively, after the date of the Cycle 1 Day 1 dose based on the Kaplan-Meier estimate.

Time frame: 6 years

Population: The safety analysis populations included all participants who received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing), and were ALK positive either by IUO (SA-ALK positive by IUO population) or by non-IUO (SA-ALK positive by non-IUO population), respectively.

PFS was defined as the time from the date of the Cycle 1 Day 1 dose to the date of the first documentation of objective tumor progression or death on study due to any cause, whichever occurred first.

Time frame: 6 years

Population: The safety analysis populations included all participants who received at least 1 dose of study medication (excluding day-7 pharmacokinetic \[PK\] dosing), and were ALK positive either by IUO (SA-ALK positive by IUO population) or by non-IUO (SA-ALK positive by non-IUO population), respectively.

The percentage of participants with maximum post-dose QTcF/QTcB (\<450, 450 - \<480, 480 - \<500, and ≥500 msec) were evaluated.

Time frame: 6 years

Population: Participants from the SA population who had a Baseline (last ECG \[electrocardiogram\] prior to Cycle 1 Day 1 dose) and ≥1 post Baseline ECG measurement and were not included in the ECG sub-study.

TTR was defined as the time (in weeks) from the date of Cycle 1 Day 1 dose to first documentation of objective tumor response (CR or PR) that was subsequently confirmed. For participants proceeding from PR to CR, the onset of PR was taken as the onset of response.

Time frame: 6 years

Population: Response-evaluable populations: defined as participants in either the SA-ALK positive by IUO population or SA-ALK positive by non-IUO population, respectively, who had adequate baseline tumor assessment.