Asian Phase I Study Of PF-03446962

The MTD was defined as the highest dose of PF-03446962 associated with the occurrence of Dose Limiting Toxicities (DLTs) in at most 1 of 6 participants with the next higher dose having at least 2/3 or 2/6 participants experiencing DLTs (that is (i.e.) Maximum Administrated Dose). DLT is defined if the participants meets the following criteria during the first 6 weeks of treatment, possibly attributable to PF-03446962. Neutropenia grade 4 (less than \[\< \])500/cubic millimeter \[mm\^ 3\]) lasting for greater than equal to (\>=) 8 days; Febrile Neutropenia \>= Grade 3; Neutropenic Infection \>= Grade 3; Grade 4 thrombocytopenia (\<25,000/mm\^3); Grade 3 thrombocytopenia (\<50,000/mm\^3) with active bleeding; Grade 3 or higher non-hematological toxicity.

Time frame: Baseline up to Week 6

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

RP2D was determined by a comprehensive assessments based on all the safety data, efficacy data, pharmacokinetics profile and biomarker data using blood and tumor samples.

Time frame: Baseline up to 28 days after last dose of study medication

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

AUC (0-28)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-28).

Time frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) for drug.

Time frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest.

Time frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: Pharmacokinetic (PK) parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest.

Time frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

Number of participants with best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST); Complete response (CR): disappearance of all lesions, Pathological lymph nodes' reduction in short axis (SA) to less than (\<)10 millimeter (mm); Partial response (PR): greater than equal to (\>=) 30% decrease in sum of longest dimensions (LD) of Target Lesions (TL) taking reference baseline sum LD; Progressive disease (PD):\>=20% (\>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of \>=1 new lesions, unequivocal progression of existing non-TL, or appearance of \>=1 new lesion; Stable disease (SD): insufficient shrinkage to qualify for PR, insufficient increase to qualify for PD taking reference smallest sum of the LD since treatment start. Confirmed response=that persist at least 4 weeks after initial documentation.

Time frame: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)

Population: Response evaluable population included all enrolled participants with measurable disease who received at least 1 dose of PF-03446962 and had an adequate baseline tumor assessment. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

Number of participant with clinical benefit response (CBR): CBR was defined as CR, PR, SD \>12 weeks, SD\<12weeks or PD according to RECIST criteria; Complete response (CR): disappearance of all lesions, Pathological lymph nodes' reduction in short axis (SA) to \<10 mm; Partial response (PR): \>=30% decrease in sum of longest dimensions (LD) of Target Lesions (TL) taking reference baseline sum LD; Progressive disease (PD):\>=20% (\>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of \>=1 new lesions, unequivocal progression of existing non-TL, or appearance of \>=1 new lesion; Stable disease (SD): insufficient shrinkage to qualify for PR, insufficient increase to qualify for PD taking reference smallest sum of the LD since treatment start.

Time frame: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)

Population: Response evaluable population included all enrolled participants with measurable disease who received at least 1 dose of PF-03446962 and had an adequate baseline tumor assessment. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

HAHA analysis was performed using validated, sensitive and specific chemiluminescence enzyme-linked immunosorbent assay (ELISA) methodology.

Time frame: Baseline, Post-dose (Day 1 of every Cycle up to 28 days after last dose) up to Cycle 30

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Laboratory abnormalities were segregated into hematology, chemistry, coagulation and urinalysis test. It had been graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) into Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Life-threatening). Participants with abnormality of any of these grades are reported.

Time frame: Baseline up to 28 days after last dose

Population: Safety analysis set included all 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. An 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 were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. AEs included both SAEs and non-serious adverse events (non-SAEs).

Time frame: Baseline up to 28 days after last dose

Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity; Grade 1 (Mild Adverse Event), Grade 2 (Moderate Adverse Event), Grade 3 (Severe Adverse Event), Grade 4 (Life- Threatening or Disabling Adverse Event), Grade 5 (Death Related to Adverse Event).

Time frame: Baseline up to 28 days after last dose

Population: Safety analysis set included 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. An 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. AEs included both SAEs and non-serious adverse events (non-SAEs). Relatedness to study drug was assessed based on investigator's discretion.

Time frame: Baseline up to 28 days after last dose

Population: Safety analysis set included 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: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

PFS was defined as the time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. PFS calculated as (Months) = (first event date minus randomization or the first dose date plus 1) divided by 30.44). PFS was calculated using the median, and 95% Confidence Intervals (CIs) and Progressive disease (PD):\>=20% (\>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of \>=1 new lesions, unequivocal progression of existing non-TL, or appearance of \>=1 new lesion.

Time frame: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)

Population: Response evaluable population included all enrolled participants with measurable disease who received at least 1 dose of PF-03446962 and had an adequate baseline tumor assessment. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

Soluble proteins related to Activin Receptor-Like Kinase 1 (ALK-1) signaling and angiogenesis signaling including Vascular adhesion molecule (VAM), Monocyte chemotactic protein 1 (MCP-1), Angiopoietin 2, Tear intercellular adhesive molecule 1 (ICAM-1), Soluble intracellular adhesion molecule 1 (SIAM-1), Soluble vascular adhesion molecule 1 (SVAM-1), Vascular endothelial growth factor A (VEGF-A), Vascular endothelial growth factor C (VEGF-C), Vascular endothelial growth factor D (VEGF-D), Soluble vascular endothelial growth factor- Receptor 1 (REC 1) (SVEGF-REC 1), Soluble vascular endothelial growth factor- REC 2 (SVEGF-REC 2), Soluble vascular endothelial growth factor- REC 3 (SVEGF-REC 3), Bone morphogenetic protein-9 (BMP-9), Endoglin, Transforming growth factor- beta 1 (TGF- Beta 1), Placental growth factor (PGF) was evaluated.

Time frame: Baseline, Day 1, 0 hour (H), 6 H Cycle 1 Day 1, Day 22 of Cycle 1, Day 1 Cycle 2, Day 1 Cycle 3 and end of treatment (up to cycle 30)

Population: Biomarker analysis population included all enrolled and treated participants with baseline and on-treatment biomarker sample analyzed. Here n= participants who were evaluable for specified biomarker at given time point for each arm, respectively.

CL is a quantitative measure of the rate at which a drug substance is removed from the body.

Time frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.

Time frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest.

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 blood concentration of a drug.

Time frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1

Population: PK parameter analysis population included all participants treated who had at least 1 of the PK parameters of interest. Here N (number of participants analyzed) signifies participants who were evaluable for this measure.