Study of PF-05212384 (Also Known as PKI-587)Administered Intravenously To Subjects With Solid Tumors

DLT was defined as any of the following events occurring during the first 28 days of study medication and considered at least possibly-related to study medication: Grade 3 nonhematologic AE (including nausea, vomiting, or diarrhea despite optimal therapy; or greater than or equal to \[\>=\] grade 3 asthenia \>2 days; or fasting serum glucose \>250 milligrams per deciliter (mg/dL) despite optimal therapy); \>=Grade 4 thrombocytopenia; Grade 3 thrombocytopenia with bleeding; Grade 4 neutropenia lasting more than 7 days; Febrile neutropenia; other Grade 4 hematologic AE; delay of treatment \>2 consecutive weeks due to toxicity. Grades were based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Time frame: Baseline up to Day 28

Population: DLT evaluable analysis set included all enrolled participants who started treatment and did not have had a major treatment deviation in the first cycle of treatment.

Criteria for laboratory test abnormality: hematology (hemoglobin \[less than {\<} 0.8\*lower limit of normal {LLN}\], platelets \[\<0.5\*LLN or greater than {\>} 1.75\*upper limit of normal {ULN}\], white blood cells \[\<0.6\*LLN or \>1.5\*ULN\], lymphocytes \[\<0.8\*LLN or \>1.2\*ULN\], total neutrophils \[\<0.8\*LLN or \>1.2\*ULN\], basophils, eosinophils, monocytes \[\>1.2\*ULN\]); coagulation \[partial thromboplastin time, prothrombin (PT), PT international ratio \[\>1.1\*ULN\]); liver function (total bilirubin \[\>1.5\*ULN\], aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase \[\>0.3\*ULN\], total protein, albumin \[\<0.8\*LLN or \>1.2\*ULN\]).

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

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 Cycle 14, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious adverse events.

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

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

Treatment-related 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. Treatment-emergent are events between first dose of study drug and up to Cycle 14, that were absent before treatment or that worsened relative to pretreatment state. Relatedness to drug was assessed by the investigator. Participants with multiple occurrences of an AE within a category were counted once within the category. AEs included both serious and non-serious adverse events.

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

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

RP2D of PF-05212384 was determined based on the safety profile including laboratory and clinical assessments and pharmacodynamics findings.

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

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

Area under the concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 168 hours (1 Week). For Cycle 2, the last PK sample for parameter calculations was on 120 hours after the Day 1 dose, however AUCtau was extrapolated to 168 hours using t1/2.

Time frame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1

Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.

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

Time frame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1

Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Area under the plasma concentration versus time curve from time zero (predose) to time of last quantifiable concentration (Clast).

Time frame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1

Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated. Here 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Tumor biopsies were taken from participants of reporting arm PF-05212384 154 mg dose level at baseline and at Cycle 1/Day 22. Biopsies were fixed in optimal cutting temperature compound and analyzed via RPMA. The biomarkers tested were phosphorylated versions of the proteins: AKT S473, AKT T308, FKHR T24 / FKHR1 T32, and STAT3. This outcome measure was planned to be analyzed only for the reporting arm Part 1 and 2: PF-05212384 154 mg, as pre-specified in protocol.

Time frame: Baseline, Day 22 of Cycle 1

Population: Tumor biopsy analysis set=all enrolled participants who had treatment \&had baseline,on-treatment tumor tissue successfully analyzed for at least 1 biomarker.N=participants evaluable for this OM. This OM was planned to analyzed only in reporting arm- Part 1 and 2:PF-05212384 154 mg.

Analysis of hair follicles was conducted using a Reverse Phase Microarrays (RPMA) assay. Phosphoprotein biomarkers measured were pAkt S473, pAkt T308, pStat3 (Y705), Ki-67, and pPRAS40 (T246).

Time frame: Baseline, 2, 3 and 72 hours (H) postdose on Day 1 of Cycle 1

Population: Hair follicle analysis set. Here, N= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for reporting arms: PF-05212384 10 mg, 21 mg, 43 mg, 89 mg, and 319 mg, as pre specified in protocol Amendment 5.

Time frame: Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)

Population: Serum biomarker analysis set. Here, N= participants evaluable for this outcome measure. Data for this outcome measure was not planned to be analyzed for reporting arms: PF-05212384 10 mg, 21 mg, 43 mg, 89 mg, and 319 mg, as pre specified in protocol Amendment 5.

Time frame: Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)

Population: Serum biomarker analysis set included all enrolled participants who started treatment and had baseline and on-treatment serum biomarker samples successfully analyzed for at least 1 biomarker.

Time frame: Baseline, Day 2 of Cycle 1, thereafter Day 1 of Cycle 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 (each cycle 28 days) , end of treatment visit (up to Cycle 14)

Population: Serum biomarker analysis set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure (OM).

Time frame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1

Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Number of Participants with maximum increase from baseline in QTcB and QTcF of \< 30 msec, between \<=30 to \<60 msec and \>=60 were reported.

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

Population: The QTc analysis set included all enrolled participants who had at least one ECG assessment after receiving PF-05212384

Biopsied tumor tissue was analyzed for alterations in the phosphoinositide-3-kinase/rat sarcoma (PI3K/RAS) signaling pathway by molecular approaches. The biomarkers studied were PIK3CA and phosphatase and tensin homolog (PTEN) by immunohistochemistry.

Time frame: Baseline

Population: Baseline tumor tissue biomarker analysis set: All enrolled patients who start treatment and had baseline tumor tissues successfully analyzed for at least one of the biomarkers. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

Objective response was defined as having complete response (CR) or Partial Response (PR) assessed by RECIST 1.1. CR was defined as disappearance of all target, non-target lesions; normalization of tumor marker level and all lymph nodes size was \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions (taking as reference the baseline sum diameters). Percentage of participants with objective response were reported.

Time frame: Baseline until disease progression or death due to any cause (up to Cycle 14 [each cycle 28 days])

Population: Response-evaluable population included participants who received at least 1 dose of study drug, had an adequate baseline tumor assessment and at least 1 post baseline disease assessment for analyses of response.

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

Time frame: Cycle 1: predose, 0.5, 2, 3, 6, 24, 72, 120 and 168 hours postdose on Day 1; Cycle 2: predose, 0.5, 24, 72, 120 hours postdose on Day 1

Population: PK parameter analysis population included all enrolled participants who received at least 1 dose of study drug and had at least 1 of the PK parameters of interest estimated.