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Tyrosine

Escalating doses of PF-02341066 will be administered orally on a continuous dosing schedule. Doses to be evaluated will range from 50 mg to 2000 mg/day administered either once or twice a day. A treatment cycle is considered to be 28 days (or 21 days depending on the cohort).

PF-02341066

600 mg QD administered from Cycle 1, Day 16 to Cycle 2, Day 1 (14 days of dosing) in combination with PF-02341066.

Multiple Dose Design: 200 mg QD administered from Cycle 1, Day 1 to Cycle 1, Day 16 (16 days) in combination with PF-02341066.

Pfizer CT.gov Call Center

PF-02341066 may work in cancer by blocking the cell growth, migration and invasion of tumor cells. PF-02341066 is a new class of drugs called c-Met/Hepatocyte growth factor receptor tyrosine kinase inhibitors. This compound is also an inhibitor of the anaplastic lymphoma kinase (called ALK) tyrosine kinase and ROS receptor tyrosine kinases. This research study is the first time PF-02341066 will be given to people. PF-02341066 is taken by mouth daily.

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

PHASE 1 SAFETY, PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF PF-02341066, A MET/HGFR SELECTIVE TYROSINE KINASE INHIBITOR, ADMINISTERED ORALLY TO PATIENTS WITH ADVANCED CANCER

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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.

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

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

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.

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

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

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

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

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.

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.

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

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

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

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

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.

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.

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.

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.

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.

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.

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Pfizer

Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety analysis set.

Participants received Crizotinib 50 milligram (mg) capsule or tablet orally once daily (QD) for up to 34 cycles (each cycle 28 days).

Low Dose Escalation Cohort: Crizotinib 50 mg QD

Participants received Crizotinib 100 mg capsule or tablet orally QD for up to 34 cycles (each cycle 28 days) and 2 mg oral dose of Midazolam along with Crizotinib 100 mg on Cycle 2 Day 1 only. Participants who did not receive Crizotinib on Day -7, received single 2 mg oral dose of Midazolam on Day -7.

Low Dose Escalation Cohort: Crizotinib 100 mg QD

Participants received Crizotinib 200 mg (2 capsules/tablet of 100 mg each) capsule/tablet orally QD for up to 34 cycles (each cycle 28 days).

Low Dose Escalation Cohort: Crizotinib 200 mg QD

Participants received Crizotinib 200 mg (2 capsules/tablet of 100 mg each) capsule/tablet orally twice daily (BID) for up to 34 cycles (each cycle 28 days).

Low Dose Escalation Cohort: Crizotinib 200 mg BID

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet BID for up to 34 cycles (each cycle 28 days).

Low Dose Escalation Cohort: Crizotinib 250 mg BID

Participants received Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet orally BID for up to 34 cycles (each cycle 28 days) and 2 mg oral dose of Midazolam along with Crizotinib 300 mg on Cycle 2 Day 1 only. Participants who did not receive Crizotinib on Day -7, received single 2 mg oral dose of Midazolam on Day -7.

Low Dose Escalation Cohort: Crizotinib 300 mg BID

Participants received Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet QD for up to 7 cycles (each cycle 28 days).

High Dose Escalation Cohort: Crizotinib 300 mg QD

Participants received Crizotinib 400 mg (4 capsules/tablet of 100 mg each) capsule/tablet QD for up to 7 cycles (each cycle 28 days).

High Dose Escalation Cohort: Crizotinib 400 mg QD

Participants received Crizotinib 500 mg (5 capsules/tablet of 100 mg each) capsule/tablet QD for up to 7 cycles (each cycle 28 days).

High Dose Escalation Cohort: Crizotinib 500 mg QD

Participants received Crizotinib 650 mg (6 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet twice daily (BID) for up to 7 cycles (each cycle 28 days).

High Dose Escalation Cohort: Crizotinib 650 mg QD

Participants received Crizotinib 800 mg (8 capsules/tablet of 100 mg each) capsule/tablet QD for up to 7 cycles (each cycle 28 days).

High Dose Escalation Cohort: Crizotinib 800 mg QD

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet orally twice daily (BID) with or without food for up to 105 cycles (each cycle 28 days).

RP2D Cohort: ROS1-Positive NSCLC: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet orally twice daily (BID) with or without food for up to 55 cycles (each cycle 28 days).

RP2D Cohort: MET Exon 14 Alterations NSCLC: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet orally twice daily (BID) with or without food for up to 101 cycles (each cycle 28 days).

RP2D Cohort: MET Amplification NSCLC: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet twice daily (BID) with or without food for up to 70 cycles (each cycle 21 days).

RP2D Cohort: ALK-Negative Cohort 1, NSCLC: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet orally BID with or without food for up to 70 cycles (each cycle 21 days).

RP2D Cohort: ALK-Negative Cohort 2, NSCLC: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet twice daily (BID) with or without food for up to 133 cycles (each cycle 28 days).

RP2D Cohort: ALK-Positive Cohort, NSCLC: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet orally twice daily (BID) with or without food for up to 54 cycles (each cycle 28 days).

RP2D Cohort: Enriched Other: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet QD from Cycle 1Day1 to Cycle 2 Day1 thereafter 250 mg BID from Cycle 2 Day 2 up to 58 cycles (each cycle 28 days). Participants also received Itraconazole 200 mg QD from Cycle 1 Day 1 to Cycle 1 Day 16.

Itraconazole Interaction Sub-study: Crizotinib 250 mg

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet twice daily (BID) with or without food from Cycle 1 Day 1 up to 13 cycles (each cycle 28 days). Participants also received commercially available Rifampin 650 mg QD from Cycle 1 Day 16 to Cycle 2 Day 1 (14 days) either one hour before or 2 hours after food.

RP2D Cohort: Rifampin Interaction: Crizotinib 250 mg +Rifampin

Participants received Crizotinib 250 mg tablet/capsule (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) orally BID from Day 1Cycle 1 up to p to 133 cycles (each cycle 28 days). Participants also received single 2 mg oral dose of Midazolam on Day -7 and another single 2-mg oral dose of Midazolam concurrently with Crizotinib on Cycle 2 Day 1.

Midazolam Interaction Cohort: Crizotinib 250

Participants received with or without food Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet QD from Cycle 1Day1 to Cycle 2 Day1 thereafter 250 mg BID from Cycle 2 Day 2 up to 58 cycles (each cycle 28 days). Participants also received Itraconazole 200 mg QD from Cycle 1 Day 1 to Cycle 1 Day 16.

RP2D Cohort: Itraconazole Interaction: Crizotinib 250 mg +Itraconazole

Participants received Crizotinib 250 mg tablet/capsule (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) orally BID with or without food from Day 1 Cycle 1 up to 133 cycles (each cycle 28 days). Participants also received single 2 mg oral dose of Midazolam on Day -7 and another single 2-mg oral dose of Midazolam concurrently with Crizotinib on Cycle 2 Day 1

RP2D Cohort: Midazolam Interaction: Crizotinib 250 mg +Midazolam

Total

less than 65 years

greater than or equals to 65 years

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

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

Pfizer ClinicalTrials.gov Call Center

Dose-Escalation Cohort: Maximum Tolerated Dose (MTD) of Crizotinib

Dose-Escalation Cohort: Recommended Phase 2 Dose (RP2D) of Crizotinib

Participants received Crizotinib 250 mg tablet/capsule (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) orally BID up to 124 months.

RP2D Cohort: Crizotinib 250 mg

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Crizotinib on Day -7

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Day -7

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 1

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 1 Day 15

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib on Cycle 2 Day 1

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".

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib Cycle 1 Day 15

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Trough Concentration (Ctrough) of Crizotinib on Cycle 2 Day 1

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Day -7

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 1

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 1 Day 15

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Maximum Observed Plasma Concentration (Cmax) of Crizotinib on Cycle 2 Day 1

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Day -7

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 1

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib on Cycle 1 Day 15

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib Cycle 2 Day 1

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.

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Plasma Decay Half-Life (t1/2) of Crizotinib on Day -7

SAEs

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet orally twice daily (BID) with or without food for up to 105 cycles (each cycle 28 days)

RP2D Cohort: ROS1-Positive NSCLC: Crizotinib 250

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

Dose-Escalation and Recommended Phase 2 Dose (RP2D) Cohort: Number of Participants With Treatment Emergent Adverse Events (TEAES) and Serious Adverse Events (SAEs)

Dose-Escalation Cohort: Number of Participants With Dose-limiting Toxicities (DLT)

Participants who did not receive Crizotinib on Day -7, received single 2 mg oral dose of Midazolam on Day -7.

Low Dose Escalation Cohort: Crizotinib 100 mg QD (Midazolam Alone)

Participants received Crizotinib 100 mg capsule or tablet orally QD along with single 2 mg oral dose of Midazolam on Cycle 2 Day 1.

Low Dose Escalation Cohort: Crizotinib 100 mg QD + Midazolam

Participants who did not receive Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet BID on Day -7, received single 2 mg oral dose of Midazolam on Day -7.

Low Dose Escalation Cohort: Crizotinib 300 mg BID (Midazolam Alone)

Participants received Crizotinib 300 mg (3 capsules/tablet of 100 mg each) capsule/tablet orally BID along with 2 mg oral dose of Midazolam on Cycle 2 Day 1.

Low Dose Escalation Cohort: Crizotinib 300 mg BID + Midazolam

Participants who did not receive Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet on Day -7, received single 2 mg oral dose of Midazolam on Day -7.

RP2D Cohort: Crizotinib 250 mg (Midazolam Alone)

Participants received Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) BID along with single 2 mg oral dose of Midazolam on Cycle 2 Day 1.

RP2D Cohort: Crizotinib 250 mg + Midazolam

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

Midazolam Interaction Cohort: Maximum Observed Plasma Concentration (Cmax) of Midazolam When Taken Alone or Taken With Crizotinib

Participants who did not receive Crizotinib 250 mg (2 capsules/tablet of 100 mg each + 1 capsule/tablet of 50 mg) capsule/tablet on Day -7, received single 2 mg oral dose of Midazolam on Day -7

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer	NCT00585195	Non-Small Cell ... Non-Small Cell ... Non-Small Cell ... Systemic Anapla... Advanced Malign...	PF-02341066 Rifampin Itraconazole	18 Years -	Pfizer
A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer	NCT00585195	Non-Small Cell ... Non-Small Cell ... Non-Small Cell ... Systemic Anapla... Advanced Malign...	PF-02341066 Rifampin Itraconazole	18 Years -	Pfizer

Spots Global Cancer Trial Database for alk rearrangements