A Study of PF-04217903 in Patients With Advanced Cancer

MTD: dose level at which 1 of 6 participants experienced dose-limiting toxicity (DLT) after 21 days of treatment (Cycle 1). DLT: grade (Gr) 2 elevated creatinine, acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable),Gr \>=3 non-hematological non-disease-related (NDR) toxicities (except alopecia,Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for \>=7 days, febrile neutropenia, neutropenic infection, inability to deliver 80 percent of planned dose during Cycle 1 due to NDR toxicities.

Time frame: Baseline up to 21 days after the start of each increased treatment dose

Population: Analysis population included all enrolled participants who received at least 1 dose of the study treatment.

DLT includes Gr 2 elevated creatinine and acute renal failure, Gr 3 thrombocytopenia with bleeding, hypertension (if unmanageable), Gr \>= 3 non-hematological non-disease-related (NDR) toxicities (except alopecia, Gr 3/4 hypophosphatemia, hyperuricemia), Gr 3/4 nausea, vomiting, diarrhea, Gr 4 neutropenia, thrombocytopenia lasting for \>= 7 days, febrile neutropenia, neutropenic infection, inability to deliver at least 80 percent of planned dose during Cycle 1 due to NDR adverse events.

Time frame: Baseline up to 21 days after the start of each increased treatment dose

Population: DLT analysis set: participants who received first cycle of study medication and did not temporarily or permanently discontinue from study medication or missed more than 3 consecutive days of PF-04217903 dosing for reasons other than DLTs within first cycle.

Time frame: Baseline up to 21 days after the start of each increased treatment dose

Population: Data was not analyzed due to insufficient number of participants enrolled.

Rac is obtained from AUCtau (Cycle 2 Day 1) divided by AUCtau (Cycle 1 Day 1). Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1

Population: The PK parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluated for this measure at specific time point for each arm group respectively.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1

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

Area under the concentration-time profile from time zero to time tau (dosing interval), where tau is equal to 12 hours.

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1

Population: The PK parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluated for this measure at specific time point for each arm group respectively.

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

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1

Population: The PK parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluated for this measure at specific time point for each arm group respectively.

F-fluoro-3'-deoxy-3'-L-fluorothymidine positron emission tomography (FLT-PET) imaging was used to assess the tumor proliferation in RP2D cohorts. Results of the FLT-PET were scored according to the methods developed by the American College of Radiology Imaging Network (ACRIN).

Time frame: Cycle 2 Day 1

Population: Data was not analyzed due to insufficient number of participants enrolled.

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hours (hrs) (just prior to evening dosing) post dose on Cycle (C) 1 Day (D) 1 and C2 D1

Population: The pharmacokinetic (PK) parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluated for this measure at specific time point for each arm group respectively.

Molar ratio of metabolite to parent area under the plasma concentration time-curve from zero (pre-dose) to end of dosing interval (MRAUCtau).

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1

Population: The PK parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluated for this measure at specific time point for each arm group respectively.

Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C2 D1

Population: The PK parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluated for this measure at specific time point for each arm group respectively.

Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and/or non target). PR were those with at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non target lesions not increased or absent.

Time frame: Baseline until disease progression up to C2 D1

Population: Efficacy analysis set included all enrolled participants who received the study treatment and had measurable disease at baseline.

Participants did not receive 200 mg twice a day dose of study treatment for this specific measure.

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1

Population: The PK parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluable for this measure.

Time frame: 0 (pre-dose), 1, 2, 4, 6, 8 and 12 hrs (just prior to evening dosing) post dose on C1 D1 and C2 D1

Population: The PK parameter analysis population included all enrolled participants who received the study medication and had at least 1 of the PK parameters of interest. 'n' signifies those participants evaluated for this measure at specific time point for each arm group respectively.