Trial Outcomes & Findings for Studying An Investigational Drug Crizotinib (PF-02341066) In Non Non-Small Cell Lung Cancer Tumors That Are Positive For Anaplastic Lymphoma Kinase (ALK) (NCT NCT01121588)

A total of 44 Anaplastic lymphoma kinase (ALK) genetic event positive participants were enrolled into the study and treated: 17 with anaplastic large cell lymphoma (ALCL), 9 with inflammatory myofibroblastic tumors (IMT), and 18 with other tumors (ALK-positive malignancies excluding non-small cell lung cancer).

The data for age was provided for the overall population and the pediatric population. Number Analyzed for Overall Population = Number of participants (regardless of age) with the corresponding type(s) of tumor, who were enrolled and treated in this study. Number Analyzed for Pediatric Population = Number of participants \<18 years of age with the corresponding type(s) of tumor, who were enrolled and treated in this study.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.