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Irinotecan

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PF-05212384 intravenous infusion weekly starting at 110 mg.

PF-05212384

PD-0325901 Oral twice daily (BID) dosing 2 mg BID 3 weeks on 1 week off

PD-0325901

PF-05212384 intravenous infusion weekly starting at 95 mg.

Irinotecan by intravenous infusion at 180 mg/m2 every two weeks (Q x 2 week)

irinotecan

Pfizer CT.gov Call Center

After the fourth protocol amendment two study arms are evaluated in this clinical protocol: PD-0325901 (oral MEK inhibitor) plus PF-05212384 (intravenous PI3K/mTOR inhibitor) and PF-05212384 plus irinotecan. The study will assess safety, pharmacokinetics and pharmacodynamics of these combinations in patients with advanced cancer. Once the maximum tolerated doses are identified, further assessment of these combinations will be done in patients with previously treated metastatic colorectal or pancreatic cancer for the PF-05212384 plus irinotecan arm and in patients with ovarian cancer or KRAS mutated non small cell lung cancer for the combination of PF-05212384 plus PD-0325901.

The study was prematurely discontinued as a result of an internal portfolio review on April 1, 2015. The decision to terminate was not due to any safety or efficacy data.

Clinical Study Of PI3K/mTOR Inhibitors In Combination With An Oral MEK Inhibitor Or Irinotecan In Patients With Advanced Cancer

A Multi-arm Phase 1 Dose Escalation Study Of The Safety, Pharmacokinetics, And Pharmacodynamics Of The Dual Pi3k/Mtor Inhibitors Pf-04691502 And Pf-05212384 In Combination With Experimental Or Approved Anticancer Agents In Patients With Advanced Cancer

DLT was defined as any of the following hematologic or non-hematologic events which were attributable to the combination study drug and occurring in the first 28-day cycle: 1) Grade 4 neutropenia lasting greater than (\>)7 days; 2) Febrile neutropenia (defined as neutropenia greater than or equal to \[≥\]Grade 3 and a body temperature ≥38.5°C); 3) Grade ≥3 neutropenic infection; 4) Grade 3 thrombocytopenia with bleeding; 5) Grade 4 thrombocytopenia; 6) Grade ≥3 toxicities; 7) Persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses during the first cycle; 8) Persistent, intolerable toxicities which resulted in delay of start of Cycle 2 by more than 2 weeks of scheduled day; 9) Persistent Grade 3 QTc prolongation (QTc \>500 msec) after correction of any reversible causes.

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.

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 which 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. AEs were graded by the NCI CTCAE (Version 4.0).

Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 hematological test abnormalities. Hematological tests included platelet count, hemoglobin, and white blood cell (WBC) count with 5- part differential.

Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 coagulation test abnormalities. Coagulation tests included partial thromboplastin time (PTT) and prothrombin time (PT) international normalized ratio (INR).

Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 chemistry test abnormalities. Chemistry tests included aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]), alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]), serum creatinine, total bilirubin, direct/indirect bilirubin, alkaline phosphatase, chloride, uric acid, phosphorus, calcium, magnesium, potassium, sodium, blood urea nitrogen (BUN) or urea, total protein, albumin, glucose, and insulin.

Number of participants with NCI CTCAE (version 4.0) grade 1 to 4 urinalysis test abnormalities for urine protein.

Number of participants with vital signs values meeting prespecified criteria. Criteria defined as: 1) absolute systolic blood pressue (SBP) less than or equal to (\<=) 100 millimeter of mercury (mmHg); 2) absolute SBP greater than or equal to (\>=) 160 mmHg, 3) SBP maximum increase of \>=20 mmHg from baseline; 4) SBP maximum increase of \>=40 mmHg from baseline; 5) SBP maximum increase of \>=60 mmHg from baseline; 6) absolute diastolic blood pressure (DBP) \<=60 mmHg; 7) absolute DBP \>=100 mmHg; 8) DBP maximum increase of \>=10 mmHg from baseline; 9) DBP maximum increase of \>=20 mmHg from baseline; 10) DBP maximum increase of \>=30 mmHg from baseline; 11) absolute heart rate (HR) \<50 beats per minute (bpm); 12) absolute HR \>120 bpm.

Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett's Formula (QTcB) and Fridericia's Formula (QTcF) .

Electrocardiogram (ECG) measurements (an average of the triplicate measurements) were used for the statistical analysis and all data presentations. QT intervals were corrected for heart rate (QTc) using Bazett's Formula (QTcB) and Fridericia's Formula (QTcF).

CR was defined as the disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis \<10 mm). PR was defined as at least a 30% decrease in the sum of the longest diameters of the targeted lesions.

Progression-free survival (PFS) was the time from first dose to date of first documentation of progression or death due to any cause.

Number of participants with expression of genes relating to PI3K, MAPK and/or Wnt pathway signaling (kirsten rat sarcoma 2 viral oncogene homolog \[KRAS\] and PTEN protein). Biopsies were obtained at baseline and Cycle 1 Day 23. Biomarker evaluation was performed on these biopsies.

Duration of response was to be calculated for participants with an objective response. Duration of PR or CR was the time from start date (date of first documentation of PR or CR) to date of first documentation of objective progression or death. CR: disappearance of a target lesions. PR: at least 30% decrease in the sum of diameters of target lesions.

Pfizer

Single oral dose of PF-04691502 4 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-04691502+PF-0325901: Arm A1 (Stage1)

Single oral dose of PF-04691502 6 mg tablet and PF 0325901 8 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily and PF 0325901 8 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-04691502+PF 0325901: Arm A2 (Stage1)

Single oral dose of PF-04691502 4 mg tablet and PF 0325901 5 mg capsule in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily and PF 0325901 5 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-04691502+PF 0325901: Arm A4 (Stage1)

Single oral dose of PF-04691502 4 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 4 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m\^2 dosed intravenously biweekly.

PF-04691502+Irinotecan: Arm B1 (Stage 1)

Single oral dose of PF-04691502 6 mg tablet in lead-in period (4 to 10 days prior to Cycle 1 Day 1), followed by PF-04691502 6 mg tablet orally once daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death. Irinotecan 180 mg/m\^2 dosed intravenously biweekly.

PF-04691502+Irinotecan: Arm B2 (Stage 1)

Participants received intravenous doses of PF-05212384 95 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m\^2 dosed intravenously biweekly.

PF-05212384+Irinotecan: Arm C1 (Stage 1)

Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m\^2 dosed intravenously biweekly.

PF-05212384+Irinotecan: Arm C2 (Stage 1)

Participants received intravenous doses of PF-05212384 130 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m\^2 dosed intravenously biweekly.

PF-05212384+Irinotecan: Arm C3 (Stage 1)

Participants received intravenous doses of PF-05212384 110 mg weekly on Days 2, 9, 16 and 23 of each 28 day cycle. Irinotecan 180 mg/m\^2 dosed intravenously biweekly. During Stage 2, only participants with metastatic colorectal cancer (mCRC) and pancreatic ductal adenocarcinoma (PDAC) were enrolled.

PF-05212384+Irinotecan: Arm C2 (Stage 2)

Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D0 (Stage 1)

Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+PD-0325901: Arm D0A (Stage 1)

Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D0B (Stage 1)

Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D1 (Stage 1)

Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D1A (Stage 1)

Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D1B (Stage 1))

Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D2 (Stage 1)

Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D2A (Stage 1)

Single intravenous dose of PF-05212384 130 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 130 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 2 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 2 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+ PD-0325901: Arm D0A (Stage 1)

Total

Age, Continuous

Sex: Female, Male

This study was terminated prematurely for strategic reasons based on an internal portfolio prioritization.

Pfizer ClinicalTrials.gov Call Center

Single intravenous dose of PF-05212384 154 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 154 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 4 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF-0325901 4 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+PD-0325901: Arm D1B (Stage 1)

Single intravenous dose of PF-05212384 110 mg in lead-in period (Day 14 prior to Cycle 1 day 1) followed by intravenous doses of PF-05212384 110 mg on Days 1, 8, 15 and 22. Single oral dose of PF 0325901 6 mg capsule in lead-in period (Day 7 to Day 1 prior to Cycle 1 Day 1), followed by PF 0325901 6 mg capsule orally twice daily continuously on Days 2-12 and 16-26 of each cycle until participants experienced unacceptable toxicity, disease progression, withdrawal from the study, or death.

PF-05212384+PD-0325901: Arm D2 (Stage 1)

All enrolled participants who started treatment and who did not have a major pre-specified treatment deviation in the first cycle of treatment in Stage 1.

Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle (28 Days)

SAEs

All enrolled participants who started treatment.

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Any AEs, Grade 1

Any AEs, Grade 2

Any AEs, Grade 3

Any AEs, Grade 4

Any AEs, Grade 5

Any AEs, Missing or Unknown

Any AEs, Total

Number of Participants With Treatment-Emergent AEs (TEAEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade

Anemia

Hemoglobin Increased

Lymphocyte Count Increased

Lymphopenia

Absolute Neutrophils

Platelets

White Blood Cells

Number of Participants With Laboratory Test Abnormalities (Hematology)

PTT (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)

PT INR (N=5,1,1,7,7,3,6,4,30,7,3,4,7,7,3,4,2)

All enrolled participants who started treatment. N=number of evaluable participants for each parameter.

Number of Participants With Laboratory Test Abnormalities (Coagulation)

Alkaline phosphatase

Total bilirubin

creatinine

hypercalcemia

hyperglycemia

hyperkalemia

hypermagnesemia

hypernatremia

hypoalbuminemia

hypocalcemia

hypoglycemia

hypokalemia

hypomagnesemia

hyponatremia

hypophosphatemia

Number of Participants With Laboratory Test Abnormalities (Chemistry)

All enrolled participants who started treatment. Number of participants analyzed=number of evaluable participants for each laboratory parameter.

Number of Participants With Laboratory Test Abnormalities (Urinalysis)

Criterion 1 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)

Criterion 2 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)

Criterion 3 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)

Criterion 4 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)

Criterion 5 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)

Criterion 6 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)

Criterion 7 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)

Criterion 8 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)

Criterion 9 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)

Criterion10 (N=5,1,1,6,7,3,6,4,31,7,3,3,7,4,3,4,1)

Criterion11 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)

Criterion12 (N=5,1,1,7,7,3,6,4,31,7,3,4,7,7,3,4,2)

All enrolled participants who started treatment. N=number of participants evaluated against criteria.

Number of Participants With Vital Signs Values Meeting Prespecified Criteria

Cycle 1 Day 2 (N=2, 6, 4, 30)

Cycle 1 Day 16 (N=3, 6, 4, 28)

Enrolled participants treated who had at least 1 of the pharmacokinetic (PK) parameters of interest estimated. N=number of participants contributing to the summary statistics.

Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C

Cycle 0 Day -14 (N=7, 3, 4, 7, 6, 3, 4, 2)

Cycle 1 Day 15 (N=5, 3, 4, 6, 5, 1, 4, 1)

Enrolled participants treated who had at least 1 of the PK parameters of interest estimated. N=number of participants contributing to the summary statistics.

Maximum Plasma Concentrations (Cmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D

Cycle 0 Day -1 (N=7, 3, 3, 7, 7, 3, 3, 2)

Cycle 1 Day 1 (N=5, 3, 3, 6, 6, 3, 4, 2)

Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D

Cycle 0 Day -7 (N=5, 1, 1)

Cycle 1 Day 12 (N=4, 1, 1)

Maximum Plasma Concentrations (Cmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A

Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A

Cycle 0 Day -7 (N=7, 7)

Cycle 1 Day 12 (N=7, 5)

Maximum Plasma Concentrations (Cmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B

Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C

Time to Reach Maximum Plasma Concentration (Tmax) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D

Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -1 and Cycle 1 Day 1 for Arm D

Time to Reach Maximum Plasma Concentration (Tmax) for PD-0325901 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A

Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A

Time to Reach Maximum Plasma Concentration (Tmax) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B

Cycle 1 Day 2 (N=1, 5, 3, 25)

Cycle 1 Day 16 (N=1, 5, 3, 20)

Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 1 Day 2 and Day 16 for Arm C

Cycle 0 Day -14 (N=5, 3, 3, 6, 6, 3, 4, 2)

Cycle 1 Day 15 (N=3, 3, 4, 6, 3, 1, 3, 1)

Terminal Elimination Half Life (t½) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D

Enrolled participants treated who had at least 1 of the pharmacokinetic (PK) parameters of interest estimated.

Terminal Elimination Half Life (t½) for PD-0325901 on Cycle 0 Day -7 for Arm A

Cycle 1 Day 12 (N=4, 0, 0)

Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm A

Cycle 0 Day -7 (N=6, 7)

Cycle 1 Day 12 (N=3, 1)

Terminal Elimination Half Life (t1/2) for PF-04691502 on Cycle 0 Day -7 and Cycle 1 Day 12 for Arm B

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D

Enrolled participants treated who had at least 1 of the PK parameters of interest estimated.

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PD-0325901 on Cycle 0 Day -7 for Arm A

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm A

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-04691502 on Cycle 0 Day -7 for Arm B

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 1 Day 2 and Cycle 1 Day 16 for Arm C

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-05212384 on Cycle 0 Day -14 and Cycle 1 Day 15 for Arm D

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PD-0325901 on Cycle 0 Day -7 for Arm A

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm A

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-04691502 on Cycle 0 Day -7 for Arm B

Maximum QTcB Interval Increase <30msec

MaximumQTcB Interval Increase >=30to<60msec

Maximum QTcB Interval Increase >=60 msec

Maximum QTcF Interval Increase <30 msec

MaximumQTcF Interval Increase >=30 to<60msec

Maximum QTcF Interval Increase >=60 msec

All participants enrolled in the study having at least one ECG assessment after receiving study drug for the respective arm.

Spots Global Cancer Trial Database for advanced metastatic cancer (solid tumors)