Studying An Investigational Drug Crizotinib (PF-02341066) In Non Non-Small Cell Lung Cancer Tumors That Are Positive For Anaplastic Lymphoma Kinase (ALK)

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious AE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication.Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

Time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)

Population: Enrolled pediatric (\<18 years old) participants who received at least 1 dose of study treatment.

An adverse event (AE) was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious AE was an AE resulting in death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care activity of daily living (ADL); Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

Time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)

Population: All enrolled participants who received at least 1 dose of study treatment.

Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Both hematology and clinical chemistry parameters were analyzed. Grades of severity were defined by CTCAE v4.0. Grade 1 = mild adverse event; Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated.

Time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)

Population: Number analyzed = Number of participants with a postbaseline value during the study treatment for this outcome measure for each specified row.

Baseline assessment was defined as the last assessment performed on or prior to the date of the first dose of study treatment. Both hematology and chemistry laboratory assessments were analyzed. Grades of severity were defined by CTCAE v4.0. Grade 1 = mild adverse event; Grade 2 = moderate adverse event; Grade 3= severe adverse event; Grade 4 = life-threatening consequences; urgent intervention indicated. Unplanned laboratory test results were also included.

Time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)

Population: Enrolled pediatric (\<18 years old) participants who received at least 1 dose of study treatment and had both baseline and post-baseline values.

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

Time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 444 weeks)

Population: All enrolled participants who received at least 1 dose of study treatment.

Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsened in severity after the first dose of study medication. Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5=death related to AE.

Time frame: From the first dose of study treatment up to 28 days after the last dose of study treatment (maximum 342 weeks)

Population: Enrolled pediatric (\<18 years old) participants who received at least 1 dose of study treatment.

Percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) (1.1) as determined by the investigators. CR = disappearance of all target lesions. PR = greater than equal to (\>=) 30% decrease in sum of target lesions taking as reference baseline sum diameters. ORR based on Cheson criteria was defined similarly however, confirmation of response was not required. If participant had tumor response assessed only by RECIST or Cheson, then ORR was based on the single result. If tumor response was assessed by both RECIST and Cheson, then ORR was reported based on tumor response by Cheson criteria unless the Cheson has indeterminate result, in which case the RECIST result was reported. Participant(s) who did not have tumor assessment results from either RECIST 1.1 or Cheson criteria reported at baseline were to be excluded from the analysis.

Time frame: From the date of first dose of study medication to the date of the first documentation of objective tumor progression or death on treatment due to any cause, whichever occured first (maximum 374 weeks)

Population: All participants who were enrolled and received at least 1 dose of study treatment, and had adequate baseline tumor assessment by either RECIST 1.1 or Cheson criteria.

Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection. The ratio is calculated as: (PF-06260182 concentration/464.33)/(Crizotinib concentration/450.34), where 464.33 is molecular weight for PF-06260182 and 450.33 is molecular weight for Crizotinib.

Time frame: Predose within -1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5

Population: Number of Participants Analyzed = participants who were enrolled and treated, had at least 1 PK blood sample collected, and were evaluable for steady-state Ctrough analysis. Number Analyzed = participants evaluable for this OM and had Ctrough data on the specific day.

DR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. CR: disappearance of all lesions; any pathological lymph nodes (target lesions \[TLs\]) or non-target lesions (non-TLs) must have reduction in short axis to \<10 mm; normalization of tumor marker level for non-TLs; PR: \>=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters; DR (in weeks) was calculated as (first date of PD or death - first date of CR or PR +1)/7. The median DR was estimated using Kaplan-Meier estimates.

Time frame: From the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first (maximum 374 weeks)

Population: Participants enrolled and treated who had baseline tumor assessment result and had confirmed CR or PR.

Number of participants with ALK translocation/fusion, amplification, mutation and overexpression at baseline assessed by technologies including fluorescence in-situ hybridization (FISH), immunohistochemistry (IHC), quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR), ALK Fusion partners assessed by FISH or PCR; ALK gene amplification assessed by FISH or array Comparative Genomic Hybridization (aCGH), ALK Mutation assessed by PCR or direct sequencing were reported.

Time frame: From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)

Population: The analysis planned to include all participant who had at least one dose of study treatment and at least one data of molecular profiling. Number Analyzed = participants who were enrolled and evaluable for this OM that had ALK genetic events at baseline.

OS is defined as the time from the date of first dose of study medication to the date of death due to any cause. OS (in months) was calculated as (date of death - date of first dose +1)/30.42. For participants still alive at the time of the analysis, for those who were lost to follow-up, and those who withdrew consent for additional follow up, the OS was censored on the last date that participants were known to be alive. Participants lacking data beyond the first dose had their OS censored at the date of first dose. The median OS was estimated using Kaplan-Meier method.

Time frame: From the first dose of study treatment to the date of death due to any cause (maximum 444 weeks)

Population: Enrolled participants who received at least 1 dose of study treatment.

The probability of survival at 6 months and 1 year, respectively, after the date of the first dose based on the Kaplan-Meier estimate.

Time frame: At 6 months and 1 year after first dose

Population: Enrolled participants who received at least 1 dose of study treatment.

Tumor sample was planned to be provided to the designated central laboratory for retrospective confirmation of ALK phosphorylation status by a Pfizer designated central laboratory. The molecular profiling results were planned to include ALK fusion/translocation, mutations, amplification and overexpression.

Time frame: From Screening 28 Days Prior to Dosing Up to End of Treatment/Withdrawal (Maximum Up to Approximately 11 Years)

Population: Analysis population included all participant who had at least one dose of study treatment and at least one data of molecular profiling at baseline and at end of treatment. Data were not collected due to that post-treatment tumor sample collection was optional per protocol and no participant had the post-treatment sample taken.

PFS was defined as the time from the date of first dose of study medication to the date of the first documentation of objective tumor progression (at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study \[this includes the baseline sum if that is the smallest on study\]). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered a sign of progression) or death on treatment due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. The median PFS was estimated using Kaplan-Meier method.

Time frame: From the date of first dose of study medication to the date of the first documentation of objective tumor progression or death on treatment due to any cause, whichever occurs first (maximum 444 weeks)

Population: All enrolled participants who received at least 1 dose of study treatment.

Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection.

Time frame: Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5

Population: Number of Participants Analyzed = participants who were enrolled and treated, had at least 1 PK blood sample collected, and were evaluable for steady-state Ctrough analysis. Number Analyzed = participants evaluable for this OM and had Ctrough data on the specific day.

Ctrough is defined as the drug concentration observed at the last planned timepoint prior to dosing. Steady state is defined as the participant receiving at least 90% of Crizotinib 500 mg daily dosing 14 days prior to the PK sample collection.

Time frame: Predose within 1.2 hours before dosing on Day 1 of Cycles 2, 3 and 5

Population: Number of Participants Analyzed = participants who were enrolled and treated, had at least 1 PK blood sample collected, and were evaluable for steady-state Ctrough analysis. Number Analyzed = participants evaluable for this OM and had Ctrough data on the specific day.