A Study Evaluating The PF-03084014 In Combination With Docetaxel In Patients With Advanced Breast Cancer

Any DLT event in Cycle 1: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia (Grade more than or equal to \[\>=\] 3 and body temperature \>=38.5 degrees Celsius); Grade \>=3 neutropenic infection; Grade \>=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia without bleeding; Grade \>=3 toxicities (except those that had not been maximally treated); Grade 3 prolongation of time from electrocardiogram (ECG) Q wave to the end of the T wave corresponding to electrical systole (QT) corrected for heart rate (QTc) which persisted after correction of reversible causes; delay of 2 weeks in receiving next scheduled cycle due to persisting treatment-related toxicities; and failure to deliver at least 80% of planned dose during first cycle due to treatment-related toxicities.

Time frame: Cycle 1 Days 1-21

Population: All enrolled participants who were eligible, received study treatment, and who either experienced DLT during the first cycle, or completed the 1-cycle observation period.

The period from study entry until disease progression, death or date of last contact. Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

Time frame: Baseline till 6 months post-dose

Population: The 6-month PFS was evaluated only for the participants in the expansion cohort (PF-03084014 100 mg BID + docetaxel 75 mg/m\^2). Due to early study termination, only 7 participants were treated in the expansion cohort.

Serum PF-03084014 pharmacokinetic (PK) parameters were calculated following twice daily (BID) doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1).

Time frame: Cycle (C) 1 Days (D) 1, 2, 8, and 21; Day 1 of subsequent cycles and at EOT (max reached: Cycle 12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

Time frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)

Population: All 7 participants who received treatment in the expansion cohort were included in the analysis. n=number of evaluable participants at the specified time point.

Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

Time frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)

Population: All 7 participants who received treatment in the expansion cohort were included in the analysis. n=number of evaluable participants at the specified time point.

Time frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)

Population: All 7 participants who received treatment in the expansion cohort were included in the analysis. At Cycle 1 Day 21, only 5 participants had available data for Ctrough.

Duration of response (DR) defined as time from start of first documented objective tumor response \[Complete Response (CR) or Partial Response (PR)\] to first documented objective tumor progression or death due to any cause, whichever occurs first. DR = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.

Time frame: Baseline up to 28-35 days after treatment discontinuation (up to Day 280)

Population: Only 4 participants had CR or PR, 2 each in the PF-03084014 100 mg BID + docetaxel 75 mg/m\^2 and PF-03084014 150 mg BID + docetaxel 75 mg/m\^2 groups.

Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AEs (TEAEs) are defined as newly occurring AEs or those worsening after first dose. AEs comprised both SAEs and non-SAEs. 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. Causality assessment was made by the investigator. Grading was per the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) version 3.0: Grade 1=mild, Grade 2=moderate, Grade 3=severe, Grade 4=life-threatening, Grade 5=death related to AE.

Time frame: Baseline up to 28-35 days after treatment discontinuation (up to Day 280)

Population: All 29 participants who received study treatment were included in the AE summarization/analysis.

Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick).

Time frame: Baseline up to 28-35 days after treatment discontinuation (up to Day 280)

Population: All 29 participants who received study treatment were included in the safety analyses.

Criteria for categorical summarization of the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT) corrected for heart rate (QTc) using Bazett's correction (QTcB) or Fridericia's correction (QTcF) included: maximum QTcB or QTcF less than or equal to (\<=) 450 milliseconds (msec), 450 to \<=480 msec, 480 to \<=500 msec, more than (\>) 500 msec; maximum QTcB or QTcF changes (increases/decreases) from baseline (BL) less than (\<) 30 msec, 30 to \<60 msec, more than or equal to (\>=) 60 msec.

Time frame: Screening, C1D1, C1D21, Day 1 of subsequent cycles, and EOT (maximum reached: C12)

Population: All 29 participants who received study treatment were analyzed for safety.

As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4.

Time frame: C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12)

Population: All treated participants who had at least 1 screening and post treatment biomarker assessment. n=number of evaluable participants for the specified biomarker at the specified time point.

OR was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than \[\<\] 10 millimeters \[mm\]). No new lesions. PR was defined as more than or equal to (\>=) 30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.

Time frame: Baseline, every 6 weeks from Cycle 2 onwards up to 26 months

Population: All 29 participants who received study treatment were included in this analysis.

Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.

Time frame: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)

Population: All 7 participants who received treatment in the expansion cohort were included in the analysis. n=number of evaluable participants at the specified time point.

Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1)

Time frame: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)

Population: All 22 participants treated in the dose escalation stage were included in the analysis. n=number of evaluable participants at the specified time point.