PF-00337210

DLTs included events occurring in Cycle 1: blood pressure of 180/110 millimeters of mercury (mmHg) or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or greater than (\>) 160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia for greater than or equal to (\>=) 7 days or \>=Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree Celsius \[degree C\] or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.

MTD: dose level at which no more than 1 of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.

MAD: dose level at which 2 or more out of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or \>160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia \>=7 days or \>= Grade 3 neutropenia associated with fever (1 reading of oral temperature \>38.5 degree C or 3 readings of oral temperature \>38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of \>1/2 teaspoon of bright red blood per day; proteinuria of \>=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; \>=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.

RP2D was determined based on the safety profile and pharmacodynamic findings. The twice daily dosing was preferred over once daily dosing for RP2D, as per investigator's discretion, due to more consistent changes in pharmacodynamic markers and greater clinical benefit observed in twice daily dosing.