A Study Of PF-04449913 Administered Alone In Select Solid Tumors

Any DLT event in Cycle 1: (1) Grade 4 neutropenia lasting more than 7 days; (2) Febrile neutropenia; (3) Grade \>=3 neutropenic infection; (4) Grade \>=3 thrombocytopenia with bleeding; (5) Grade 4 thrombocytopenia lasting more than 7 days; (6) Grade \>=3 non-hematologic toxicity; (7) Failure to deliver at least 80% of the planned doses due to toxicities attributable to PF-04449913

Time frame: Baseline up to end of Cycle 1 (Study Day 28)

Population: Per-Protocol Analysis Set: all enrolled participants who received at least 1 dose of study medication and did not have major treatment deviations during Cycle 1.

Accumulation ratio was calculated as AUCtau at steady state (Cycle 1/Day 25)/AUCtau on Study Day 1

Time frame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1, and pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes.

Time frame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Time frame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

AUCtau of PF-04449913 on Cycle 1/Day 1 has been reported. AUCtau is defined as area under the curve from time 0 to tau, where tau is the dosing interval of 24 hours.

Time frame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

AUCtau of PF-04449913 on Cycle 1/Day 25 has been reported. AUCtau is defined as area under the curve from time 0 to tau, where tau is the dosing interval of 24 hours.

Time frame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Time frame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Duration from date of first documentation of objective response to date of first documentation of disease progression or death. Progression was defined using RECIST 1.1 as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. DR was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first objective response that was subsequently confirmed plus 1).

Time frame: Baseline up to Cycle 14 (each cycle 28 days)

Population: This OM was planned for expansion cohort only. Since none of the participants were enrolled in expansion cohort, no data was collected for duration of response and thus the outcome measure was not performed.

Ribonucleic acid (RNA) was extracted from skin samples and complementary deoxyribonucleic acid (cDNA) was prepared. Gene expression was measured using custom Taqman low density array (TLDA) cards run on the Applied Biosystems ViiATM 7 system. The ratio for each participant at each dosing level was calculated at C1D15 to baseline assay readout (C1D1), and the mean of it is reported in this outcome measure.

Time frame: Baseline and Cycle 1/Day 15

Population: Pharmacodynamic (PD) Analysis Set: all enrolled participants who received at least 1 dose of study medication, and had baseline and at least 1 on-treatment PD result.

Cmax of PF-04449913 on Cycle 1/Day 1 has been reported.

Time frame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Cmax of PF-04449913 on Cycle 1/Day 25 has been reported.

Time frame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. QTcF was calculated. Participants with maximum decrease from baseline of \<30 msec, 30 to \<60 msec and \>=60 msec were summarized.

Time frame: Baseline up to Cycle 14 (each cycle 28 days)

Population: QTc Analysis Set: all enrolled participants who had at least 1 ECG assessment after receiving at least 1 dose of study medication.

Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole (QT) was corrected for heart rate (QTc). QTc using Fridericia's formula (QTcF) was calculated. Participants with maximum increase from baseline of less than (\<) 30 millisecond (msec), 30 to \<60 msec and \>=60 msec were summarized.

Time frame: Baseline up to Cycle 14 (each cycle 28 days)

Population: QTc Analysis Set: all enrolled participants who had at least 1 ECG assessment after receiving at least 1 dose of study medication.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. Participants with post-baseline absolute QTcF values \>=500 msec were summarized.

Time frame: Baseline up to Cycle 14 (each cycle 28 days)

Population: QTc Analysis Set: all enrolled participants who had at least 1 ECG assessment after receiving at least 1 dose of study medication.

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Confirmed responses were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as complete disappearance of all target lesions with the exception of nodal disease. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions.

Time frame: Baseline up to Cycle 14 (each cycle 28 days)

Population: Efficacy Analysis Set: all enrolled participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events occurred between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than one occurrence in the same preferred term event category, only the worst CTCAE grade was reported. Grades as per NCI CTCAE, v4.0 were classified as: Grade 1- mild, Grade 2- moderate, Grade 3- severe, Grade 4- life threatening, and Grade 5- death.

Time frame: Baseline up to 28 days post last dose of study medication (maximum duration: 14 cycles [each cycle of 28 days])

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-related AEs are events that were assessed by the investigator as related to study medication. If the same participant in a given treatment had more than one occurrence in the same preferred term event category, only the worst CTCAE grade was reported. Grades as per NCI CTCAE, v4.0 were classified as: Grade 1- mild, Grade 2- moderate, Grade 3- severe, Grade 4- life threatening, and Grade 5- death.

Time frame: Baseline up to 28 days post last dose of study medication (maximum duration: 14 cycles [each cycle of 28 days])

Population: Safety Analysis Set: all enrolled participants who received at least 1 dose of study medication.

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

Time frame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Time from Cycle 1/Day 1 to first documentation of disease progression or to death due to any cause, whichever occurred first. Progression was defined using RECIST 1.1 as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. PFS (days) was calculated as (first event date minus the date of first dose of study medication plus 1).

Time frame: Baseline up to Cycle 14 (each cycle 28 days)

Population: This OM was planned for expansion cohort only. Since none of the participants were enrolled in expansion cohort, no data was collected for progression free survival and thus the outcome measure was not performed.

Time from Cycle 1/Day 1 to first documentation of disease progression. Progression was defined using RECIST 1.1 as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm. TTP (days) was calculated as (first event date minus the date of first dose of study medication plus 1).

Time frame: Baseline up to Cycle 14 (each cycle 28 days)

Population: This OM was planned for expansion cohort only. Since none of the participants were enrolled in expansion cohort, no data was collected for time to progression and thus the outcome measure was not performed.

Tmax of PF-04449913 on Cycle 1/Day 1 has been reported.

Time frame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure

Tmax of PF-04449913 on Cycle 1/Day 25 has been reported.

Time frame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25

Population: PK Analysis Set: all treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for the outcome measure