A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau).

Time frame: pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)

Population: PK parameter population was defined as all participants in the Rifampin interaction cohort safety population who satisfied following criteria for Cycle 1 Day 15 or Cycle 2 Day 1: a) had at least 1 of the primary PK parameters of Crizotinib (AUCtau and Cmax). b) received adequate dosing prior to PK sampling. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure.

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).

Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

Population: The PK concentration population of midazolam included all participants treated with midazolam (including Day -7 dose) who have at least 1 concentration of midazolam.

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time frame: Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be collected for low dose escalation cohort (excluding Crizotinib 50 mg QD, Crizotinib 200 mg QD and Crizotinib 250 mg BID arms) and combined RP2D cohort and was not planned to be collected for high dose escalation cohort.

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

Population: The PK parameter analysis population included all participants treated (including Day -7 dose) who have at least 1 of the PK parameters of interest for Crizotinib. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data for this outcome measures was planned to be collected for individual arms of dose escalation cohorts and combined RP2D Cohort.

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

Population: The PK parameter analysis population included all participants treated (including Day -7 dose) who have at least 1 of the PK parameters of interest for Crizotinib. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data for this outcome measures was planned to be collected for individual arms of dose escalation cohorts and combined RP2D Cohort.

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dose and 24 hours for QD dose.

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be reported for individual arms of low and high dose escalation and combined RP2D Cohort excluding Low Dose Escalation Cohort: Crizotinib 100 mg QD arm.

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time (0-inf).

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Population: Pharmacokinetic (PK) parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Overall number of participants analyzed (N) signifies participants evaluable for this outcome measure (OM). Data for this OM was planned to be collected for individual arms of low and high dose escalation and combined RP2D Cohort excluding Low Dose Escalation Cohort: Crizotinib 100 mg QD arm.

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time frame: Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be collected for low dose escalation cohort (excluding Crizotinib 50 mg QD, Crizotinib 200 mg QD and Crizotinib 250 mg BID arms) and combined RP2D cohort and was not planned to be collected for high dose escalation cohort.

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

Population: The PK parameter analysis population included all participants treated (including Day -7 dose) who have at least 1 of the PK parameters of interest for Crizotinib. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data for this outcome measures was planned to be collected for individual arms of dose escalation cohorts (both low and high) and combined RP2D Cohort.

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

Population: The PK parameter analysis population included all participants treated (including Day -7 dose) who have at least 1 of the PK parameters of interest for Crizotinib. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data for this outcome measures was planned to be collected for individual arms of dose escalation cohorts (both low and high) and combined RP2D Cohort.

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Population: PK parameter analysis population set. N=participants evaluable for this outcome measure. Data for this OM was planned to be collected for dose escalation cohorts (both low and high) and combined RP2D Cohort excluding Low Dose Escalation Cohort: Crizotinib 100 mg QD cohort arms.

An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. 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; medically important events. AEs included both serious and all non-serious adverse events. TEAEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration.

Time frame: up to 189 Months

Population: SA set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1.

Plasma decay half-life is the time measured for the plasma concentration of Crizotinib to decrease by one half.

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be collected for individual arms of low and high dose escalation cohort and combined RP2D cohort excluding Low Dose Escalation Cohort: Crizotinib 100 mg QD arm.

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 2 Day 1

Population: The PK parameter analysis population included all participants treated (including Day -7 dose) who have at least 1 of the PK parameters of interest for Crizotinib. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data for this outcome measures was planned to be collected for individual arms of dose escalation cohorts (both low and high) and combined RP2D Cohort.

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time frame: Pre-dose, 2, 4 and 6 hours post dose on Cycle 1 Day 1

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be collected for low dose escalation cohorts (excluding Crizotinib 50 mg QD, Crizotinib 200 mg QD and Crizotinib 250 mg BID arms) and combined RP2D cohort and was not planned to be collected for high dose escalation cohort.

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15

Population: The PK parameter analysis population included all participants treated (including Day -7 dose) who have at least 1 of the PK parameters of interest for Crizotinib. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data for this outcome measures was planned to be collected for individual arms of dose escalation cohorts (both low and high) and combined RP2D Cohort.

Tmax was defined as the time to reach the observed maximum plasma concentration (Cmax).

Time frame: Pre-dose, 1, 2, 4, 6, 8, 9, 24, 48 and any two time points (72, 96, 120 and 144 hours) post-dose on Day -7

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be collected for individual arms of low and high dose escalation cohorts (excluding 'Low Dose Escalation Cohort: Crizotinib 100 mg QD' arm) and combined RP2D.

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time frame: Pre-dose on Cycle 1 Day 15

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be collected for individual arms of low dose escalation and combined RP2D Cohort and not planned to be collected for high dose escalation cohort.

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time frame: Pre-dose on Cycle 2 Day 1

Population: PK parameter analysis population included all participants treated (including Day -7 dose) who had at least 1 of the PK parameters of interest for Crizotinib. Here, N signifies participants evaluable for this OM. Data for this OM was planned to be collected for individual arms of low dose escalation and combined RP2D Cohort and not planned to be collected for high dose escalation cohort.

MTD: Dose level at which at most 1 of 6 participants experienced DLT within and including 28 days of treatment (during Cycle 1 \[1 cycle=28 days\]) with next higher dose having at least 2/3 or 2/6 participants experiencing a DLT. DLT was defined as any of following: Hematologic toxicities- 1) prolonged grade 4 neutropenia for \>7 days. 2) Febrile neutropenia: grade 4 neutropenia with fever greater than (\>) 38.5 degree Celsius, both sustained over a 24 hour period (3) neutropenic infection: greater than or equal to (\>=) Grade 3 neutropenia with Grade \>=3 infection. (4) Grade \>=3 thrombocytopenia with bleeding/grade 4 lasting \>=7 days. Other non-hematologic toxicity included: Grade 3/4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure \[less than (\<) 140/90 millimeter of mercury, and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting/diarrhea must persist at grade 3/4 despite maximal medical therapy.

Time frame: Cycle 1 (28 days)

Population: Safety analysis (SA) set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1.

Dose-limiting toxicity (DLT) was defined as any of the following: Hematologic- prolonged grade 4 neutropenia for \>7 days. Febrile neutropenia, defined as grade 4 neutropenia with fever greater than (\>)38.5 degree Celsius, both sustained over a 24 hour period, neutropenic infection: greater than or equal to (\>=)Grade 3 neutropenia with Grade \>=3 infection. Grade \>=3 thrombocytopenia with bleeding or grade 4 lasting \>=7 days Lymphopenia was not considered a DLT unless accompanied by infection. Other non-hematologic toxicity: Grade 3 or 4 toxicities (except for alopecia, Grade 3/4 hypophosphatemia, grade 3 hypertension with controlled blood pressure \[less than (\<) 140/90\], and Grade 3/4 hyperuricemia without signs and symptoms of gout). Nausea, vomiting or diarrhea must persist at grade 3 or 4 despite maximal medical therapy.

Time frame: Cycle 1 (28 days)

Population: SA set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1.

RP2D was defined as a dose below or equal to MTD, at which crizotinib was unlikely to cause a significant inhibition of CYP3A4 activity.

Time frame: Cycle 1 (28 days)

Population: Safety analysis (SA) set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1.

Geometric mean of ratio (Cycle 12 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 12 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle 15 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 15 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this outcome measure.

Geometric mean of ratio (Cycle 18 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 18 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle1Day15/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Time frame: Baseline, Cycle 1 Day 15

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle 21 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 21 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle 24 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 24 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle 27 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 27 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this outcome measure.

Geometric mean of ratio (Cycle 2 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Time frame: Baseline, Cycle 2 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle 30 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 30 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this outcome measure.

Geometric mean of ratio (Cycle 4 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Time frame: Baseline, Cycle 4 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle 6 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts.

Time frame: Baseline, Cycle 6 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (Cycle 9 Day 1/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, Cycle 9 Day 1

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Geometric mean of ratio (End of treatment/Baseline) of hypogonadism parameters (total testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone, dihydroepiandrosterone sulfate, estradiol and prolactin) levels in males was analyzed. Data for this outcome measure was planned to be collected for combined RP2D Cohort only, excluding arms of low and high dose escalation cohorts. 95% CI should be interpreted with cautions due to the limited sample size at this time point.

Time frame: Baseline, End of Treatment (28 days post last dose)

Population: Hypogonadism test evaluable population: Male participants who had completed screening, had received at least 1 dose of crizotinib on Cycle 1 Day 1, had at least 1 post baseline visit data for at least total testosterone, free testosterone, SHBG and included male participants of MET amplification and enriched other Cohort following approval of protocol amendment number 21. N =participants evaluable for this OM and 'number analyzed' =participants with available data for each specified category.

Area under the plasma concentration versus time curve from time 0 to end of dosing interval (AUCtau), where dosing interval is 24 hours.

Time frame: pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

Population: PK parameter evaluable population included participants who had at least 1 of the PK parameters of Crizotinib (AUCtau or Cmax) and had received 10 consecutive doses of both Crizotinib 250 mg QD and itraconazole 200 mg QD immediately prior to end of Crizotinib 250 mg + Itraconazole treatment as well as 10 consecutive doses of Crizotinib 250 mg QD prior to end of Crizotinib 250 mg + Itraconazole treatment. Overall number of participants analyzed =participants evaluable for this outcome measure.

Time frame: pre-dose, 1, 2, 4, 6, 8, 9 and 24 hours post dose on Cycle 1 Day 15 (Crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

Population: PK parameter evaluable population included participants who had at least 1 of the PK parameters of Crizotinib (AUCtau or Cmax) and had received 10 consecutive doses of both Crizotinib 250 mg QD and itraconazole 200 mg QD immediately prior to end of Crizotinib 250 mg + Itraconazole treatment as well as 10 consecutive doses of Crizotinib 250 mg QD prior to end of Crizotinib 250 mg + Itraconazole treatment. Overall number of participants analyzed =participants evaluable for this outcome measure.

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time frame: pre-dose on Cycle 1 Day 15 (crizotinib with itraconazole) and Cycle 2 Day 1 (itraconazole alone)

Population: PK parameter evaluable population included participants who had at least 1 of the PK parameters of Crizotinib (AUCtau or Cmax) and had received 10 consecutive doses of both Crizotinib 250 mg QD and itraconazole 200 mg QD immediately prior to end of Crizotinib 250 mg + Itraconazole treatment as well as 10 consecutive doses of Crizotinib 250 mg QD prior to end of Crizotinib 250 mg + Itraconazole treatment. Overall number of participants analyzed =participants evaluable for this outcome measure.

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time frame: pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Day -7 (midazolam alone arm), pre-dose, 0.5, 1, 2, 4, 6, 8, 9, and 24 hours post dose on Cycle 2 Day 1 (midazolam with crizotinib arm)

Population: The PK concentration population of midazolam included all participants treated with midazolam (including Day -7 dose) who have at least 1 concentration of midazolam.

Probability of survival was defined as the probability of being alive at Month 12.

Time frame: Month 12

Population: SA set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

Probability of survival was defined as the probability of being alive at Month 6.

Time frame: Month 6

Population: SA set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

Duration of response (DoR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Time frame: From first documentation of response to date of PD or death due to any cause (up to 172 months)

Population: Response-evaluable population was defined as all participants in the SA set who had an adequate baseline disease assessment and had met 1 of the following 2 criteria: a) Had at least one post-baseline disease assessment b) withdrew from the trial or experienced progression/death at any time on study. Here, Overall number of participants analyzed signifies number of participants who were objective responders. Data was planned to be analyzed for reported arms only.

OS was defined as the time from randomization to death due to any cause.

Time frame: From randomization date to the date of death (up to 172 Months)

Population: SA set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

Disease control was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Time frame: Week 16

Population: Response-evaluable population was defined as all participants in the SA set who had an adequate baseline disease assessment and had met 1 of the following 2 criteria: a) Had at least one post-baseline disease assessment b) withdrew from the trial or experienced progression/death at any time on study. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

Disease control was defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Time frame: Week 8

Population: Response-evaluable population was defined as all participants in the SA set who had an adequate baseline disease assessment and had met 1 of the following 2 criteria: a) Had at least one post-baseline disease assessment b) withdrew from the trial or experienced progression/death at any time on study. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

ORR was defined as participants with a best overall response of complete response (CR) or partial response (PR) divided by the total number of evaluable participants per RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response.

Time frame: Baseline up to 172 months

Population: Response-evaluable population was defined as all participants in the SA set who had an adequate baseline disease assessment and had met 1 of the following 2 criteria: a) Had at least one post-baseline disease assessment b) withdrew from the trial or experienced progression/death at any time on study. Here, Overall number of participants Analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

Probability of being event free (event defined as PD or death due to any cause) at 6 months after the first dose of crizotinib was reported. PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Time frame: From randomization to 6 months

Population: SA set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1. Here, Overall Number of Participants Analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

Progression free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause RECIST version 1.0 (RECIST1.1 for ALK-negative NSCLC cohort 1 and ALK-negative NSCLC cohort 2). PD: \>=20% increase in the sum of the longest diameter of target lesions taking as references the smallest sum longest diameter recorded since the treatment started, unequivocal progression of existing non-target lesions, or the appearance of 1 or more new lesions.

Time frame: From randomization until PD or death, whichever occurred first (up to 172 months)

Population: SA set included all enrolled participants who received at least one dose of Crizotinib on Cycle 1 Day 1. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure. Data was planned to be analyzed for reported arms only.

TTR: time between first dose until first documented response of PR or CR. PR: At least a 30% decrease in the sum of the longest diameters of target lesions (taking as reference the baseline sum), without progression of non-target lesions and no appearance of new lesions indicated partial response. CR: Disappearance of all target and non-target lesions, normalization of tumor marker levels, and no appearance of new lesions indicated complete response.

Time frame: From first dose until first documented response of PR or CR (up to 172 months)

Population: Response-evaluable population was defined as all participants in the SA set who had an adequate baseline disease assessment and had met 1 of the following 2 criteria: a) Had at least one post-baseline disease assessment b) withdrew from the trial or experienced progression/death at any time on study. Here, Overall number of participants analyzed signifies number of participants who were objective responders. Data was planned to be analyzed for reported arms only.

Ctrough refers to plasma concentration of Crizotinib observed just before treatment administration.

Time frame: pre-dose on Cycle 1 Day 15 (Crizotinib alone arm) and Cycle 2 Day 1 (Crizotinib with Rifampin arm)

Population: PK parameter population was defined as all participants in the Rifampin interaction cohort safety population who satisfied following criteria for Cycle 1 Day 15 or Cycle 2 Day 1: a) had at least 1 of the primary PK parameters of Crizotinib (AUCtau and Cmax). b) Received adequate dosing prior to PK sampling. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure.

Time frame: pre-dose, 2, 4, 6, 8 and 10 hours on Cycle 1 Day 15 (Crizotinib alone) and Cycle 2 Day 1 (Crizotinib with Rifampin)

Population: PK parameter population was defined as all participants in the Rifampin interaction cohort safety population who satisfied following criteria for Cycle 1 Day 15 or Cycle 2 Day 1: a) had at least 1 of the primary PK parameters of Crizotinib (AUCtau and Cmax). b) Received adequate dosing prior to PK sampling. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure.

AUC0-24 of Crizotinib was defined as the area under the free plasma concentration time curve from time 0 to 24 hours post-dose.

Time frame: pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7

Population: The food effect analysis set included all participants treated (including Day -7 dose) and in the RP2D cohort who had received a dose of crizotinib under fed conditions and for which at least 1 PK parameter of interest (Cmax or AUC) was available. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure.

Cmax is defined as the observed maximum plasma concentration post drug administration.

Time frame: pre-dose, 1, 2, 4, 6, 8, 9, and 24 hours post-dose on Day -7

Population: The food effect analysis set included all participants treated (including Day -7 dose) and in the RP2D cohort who had received a dose of crizotinib under fed conditions and for which at least 1 PK parameter of interest (Cmax or AUC) was available. Here, Overall number of participants analyzed signifies number of participants evaluable for this outcome measure.