Breast Neoplasms, Carcinoma, Renal Cell, Colorectal Neoplasms, Liver Neoplasms, Melanoma, Mesothelioma, Neoplasms, Squamous Cell, Pancreatic Neoplasms, Prostate Neoplasms
Conditions
Keywords
efficacy, safety, pharmacokinetics, dose escalation, dose expansion, open-label, TGFb, transforming growth factor beta, breast cancer, prostate cancer, CRPC, metastatic, advanced, adenocarcinoma
Brief summary
A Phase 1 dose escalation and expansion study evaluating safety, tolerability and pharmacokinetics of PF-06952229 in adult patients with advanced solid tumors.
Detailed description
This is a Phase 1, open label, multi center, multiple dose, dose escalation and expansion, safety, tolerability, PK, and pharmacodynamics study of PF 06952229 in previously treated patients with advanced or metastatic cancers that may have high TGFbeta signatures and EMT expression. The study includes Parts 1A and 1B, which are dose-escalation for monotherapy and combination therapy with enzalutamide, respectively, and Parts 2A and 2B, which are dose expansion for monotherapy and combination therapy with enzalutamide, respectively.
Interventions
DRUGPF-06952229
Oral 7 days on / 7 days off - 28 day cycles (Part 1)
DRUGEnzalutamide
Prostate Cancer (Part 2). 160mg, capsules, orally, daily
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. For Part 1A: Histological or cytological diagnosis of a solid tumor that is advanced/metastatic, patients are intolerant to standard treatment, resistant to standard therapy or for which no standard therapy is available for the following tumor types: Breast cancer; Prostate cancer (mCRPC testosterone less than 50 ng/dL); Squamous cell cancer of the head and neck; Melanoma; Mesothelioma; Pancreatic cancer; Colorectal cancer; Renal cell carcinoma; Hepatocellular cancer. 2. For Part 1B: * histological or cytological diagnosis of mCRPC 3 Part 2A and Part 2B: * Histologically or cytologically confirmed prostate adenocarcinoma metastatic disease. * Effective castration with serum testosterone levels 0.5 ng/mL (1.7 nmol/L). * Having received 3 or more cycles of prior docetaxel therapy (before or after abiraterone). * Having PD while receiving abiraterone acetate within 12 months of abiraterone treatment initiation. * Progressive disease (PD) by: 1. Progression in measurable disease per RECIST 1.1 criteria. Patient with measurable disease must have at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be at least 10 mm when measured by computed tomography (CT) (CT scan thickness no greater than 5 mm) or magnetic resonance imaging (MRI). Lymph nodes should be greater than or equal to 15 mm in short axis. As defined by PCWG2, if lymph node metastasis is the only evidence of metastasis, it must be greater than or equal to 20 mm in diameter when measured by spiral CT or MRI. Previously irradiated lesions, primary prostate lesion, and bone lesions will be considered non-measurable disease, or 2. Appearance of 2 or more new bone lesions (PCWG2). They must be confirmed by other imaging modalities (CT; MRI) if ambiguous results, or 3. Rising PSA defined (PCWG2) as at least 2 consecutive rises in PSA to be documented over a reference value (measure 1) taken at least 1 week apart. • Prior abiraterone acetate must be stopped at least 2 weeks before study treatment. 4\. Patients must have recently obtained archival tumor tissue available for submission to the sponsor (except for Part 2A - monotherapy dose expansion). Patients enrolled in Part 1 and Part 2 should have access to their archival formalin-fixed paraffin-embedded material, collected within 6 months of screening, containing tumor that is of diagnostic quality and representative of their diagnosed malignancy or whenever possible, consent to undergo a biopsy during screening. The sponsor should be contacted if obtaining a new biopsy is not medically feasible for approval to enroll, prior to initiating screening activities. 5\. Patients entering the study in the subgroup(s) requiring mandatory pre- and on treatment tumor biopsies in Part 2A and 2B must have a tumor amenable to biopsy and consent to these planned biopsy procedures. The sponsor should be contacted if obtaining a pre-treatment and on treatment biopsies is not medically feasible for approval to enroll, prior to initiating screening activities. 6\. Age 18 years or older 7. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1. 8. Adequate bone marrow function (see Appendix 3), including: * Absolute Neutrophil Count (ANC) greater than or equal to 1,500/mm3; * Platelets greater than or equal to 100,000/mm3; * Hemoglobin greater than or equal to 9 g/dL. 9. Adequate renal function, including serum creatinine less than or equal to 1.5 x upper limit of normal (ULN) or estimated creatinine clearance greater than or equal to 60 mL/min as calculated using the method standard for the institution. In equivocal cases, a 24 hour urine collection test can be used to estimate the creatinine clearance more accurately. In Part 2: Serum creatinine of less than or equal to 3.0 x upper limit of normal. 10\. Adequate liver function, including: * Total serum bilirubin less than or equal to 0.5 x ULN unless the patient has documented Gilbert syndrome; * Aspartate and alanine aminotransferase (AST and ALT) less than or equal to 2.5 x ULN less than or equal to 5.0 x ULN if there is liver involvement by the tumor; * Alkaline phosphatase less than or equal 2.5 x ULN less than or equal to 5 x ULN in case of bone metastasis). 11\. Serum phosphate within normal range (if abnormal, must be nonclinically significant per the Investigator and approval for patient inclusion after agreement from sponsor. 12\. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1 except for alopecia and those listed in the specific
Exclusion criteria
. 13\. For Part 1A monotherapy dose escalation: serum pregnancy test (for females of childbearing potential) negative at screening. 14\. For Part 1A monotherapy dose escalation: female patients of nonchildbearing potential must meet at least 1 of the following criteria: * Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and must have a serum follicle stimulating hormone level confirming the postmenopausal state; * Have undergone a documented hysterectomy and/or bilateral oophorectomy; * Have medically confirmed ovarian failure. All other female patients (including female patients with tubal ligations) are considered to be of childbearing potential. 15\. Evidence of a personally signed and dated informed consent document indicating that the patient has been informed of all pertinent aspects of the study. 16\. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | Within 28 days of first dose or until the participant completed the first cycle of therapy if there were treatment delayed (on average 28 days). | First cycle DLTs were utilized to determine the max tolerated dose and future escalations or deescalations. Any of the following adverse events occurred in the first cycle of treatment which were clinically significant were classified as DLTs: Hematologic: Thrombocytopenia Grade 4 for \>=7 days, or Grade 3 or 4 associated with \>= Grade 2 clinically significant bleeding or requiring platelet transfusion; Neutropenia Grade 4 for \>=7 days; Grade\>=3 neutropenia with infection; Anemia Grade 4 or Grade 3 requiring blood transfusion. Nonhematologic: Grade\>=3 toxicities that were considered clinically significant; Alanine aminotransferase/aspartate aminotransferase\>3x the upper limit of normal (ULN) with bilirubin\>2x ULN without another explanation; Grade 3 nausea, vomiting or diarrhea that did not resolve within 4 days despite maximal supportive therapy. Nonhematologic and Non-Hepatic: Any toxicity caused\>= 2 weeks of dose delay or preventing participants from receiving 75% of study drug. |
| Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Baseline up to 28 days after last dose of study treatment ( up to approximately 2 years) | 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 death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. |
| Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | Baseline up to 28 days after last dose of study treatment ( up to approximately 2 years) | Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test \[for all female participants\]) and urine (urine pregnancy test \[for all female participants\]). Clinical significance of laboratory parameters was determined at the investigator's discretion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2 | AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1B) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2 | AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1A) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2 | AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1B) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2 | AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. |
| Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. CL/F = Dose/AUCinf for single dose; CL/F = Dose/AUCtau for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. |
| Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Cmax was directly observed from data. Cmax was defined as maximum observed plasma concentration. |
| Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Vz/F was defined as apparent volume of distribution. Vz/F = Dose / (AUCinf\* kel) for single dose; Vz/F = Dose / (AUCtau\* kel) for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. Kel was defined as terminal phase rate constant. |
| Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1B) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2 | Vz/F was defined as apparent volume of distribution. Vz/F = Dose / (AUCinf\* kel) for single dose; Vz/F = Dose / (AUCtau\* kel) for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. Kel was defined as terminal phase rate constant. |
| Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Plasma terminal elimination half-life (T1/2) was the time measured for the plasma concentration to decrease by one half of its initial concentration. |
| Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1B) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2 | Plasma terminal elimination half-life (T1/2) was the time measured for the plasma concentration to decrease by one half of its initial concentration. |
| Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | Baseline, Cycle 1 Day 1 (at the beginning of Cycle 1), and then every 3 cycles (each cycle is 28 days) until end of treatment (an average of 1 year) | Prostate-specific antigen decline by more than 50% from baseline was analyzed. PSA partial response was defined as a ≥50% decline in PSA from Cycle 1 Day 1 (baseline) PSA value. This PSA decline much be confirmed to be sustained by a second PSA value obtained 4 or more weeks later. |
| Percentage of Participants With Objective Response | Baseline and every 8 to 12 weeks through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years. | Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). Complete response was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). All target lesions must be assessed. Partial response was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed. |
| Apparent Clearance (CL/F) of PF-06952229 (Part 1B) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. CL/F = Dose/AUCinf for single dose; CL/F = Dose/AUCtau for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. |
| Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Cmax was directly observed from data. Cmax was defined as maximum observed plasma concentration. |
| Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2. | Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence. |
Countries
United States
Participant flow
Pre-assignment details
A total of 42 participants were enrolled in the Part 1A and all were treated. A total of 7 participants were enrolled in Part 1B and all were treated.
Participants by arm
| Arm | Count |
|---|---|
| Part 1A: PF-06952229 20mg Monotherapy PF-06952229 was administered at a dose of 20 mg orally twice daily (BID) for 7 days on, 7 days off for each Cycle (one cycle = 28 days). | 1 |
| Part 1A: PF-06952229 40mg Monotherapy PF-06952229 was administered at a dose of 40 mg orally BID for 7 days on, 7 days off for each Cycle (one cycle = 28 days). | 1 |
| Part 1A: PF-06952229 80mg Monotherapy PF-06952229 was administered at a dose of 80 mg orally BID for 7 days on, 7 days off for each Cycle (one cycle = 28 days). | 1 |
| Part 1A: PF-06952229 150mg Monotherapy PF-06952229 was administered at a dose of 150 mg orally BID for 7 days on, 7 days off for each Cycle (one cycle = 28 days). | 5 |
| Part 1A: PF-06952229 250mg Monotherapy PF-06952229 was administered at a dose of 250 mg orally BID for 7 days on, 7 days off for each Cycle (one cycle = 28 days). | 13 |
| Part 1A: PF-06952229 375mg Monotherapy PF-06952229 was administered at a dose of 375 mg orally BID for 7 days on, 7 days off for each Cycle (one cycle = 28 days). | 17 |
| Part 1A: PF-06952229 500mg Monotherapy PF-06952229 was administered at a dose of 500 mg orally BID for 7 days on, 7 days off for each Cycle (one cycle = 28 days). | 4 |
| Part 1B: PF-06952229 250mg + Enzalutamide PF-06952229 was administered at a dose of 250 mg orally twice daily (BID) for 7 days on, 7 days off for each Cycle (one cycle = 28 days) in combination with enzalutamide at 160 mg orally once a day (QD) as continuous daily dosing. | 4 |
| Part 1B: PF-06952229 375mg + Enzalutamide PF-06952229 was administered at a dose of 375 mg orally twice daily (BID) for 7 days on, 7 days off for each Cycle (one cycle = 28 days) in combination with enzalutamide at 160 mg orally QD as continuous daily dosing. | 3 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 1 | 1 | 4 | 0 | 1 | 1 |
| Overall Study | Global Deterioration of Health Status | 0 | 0 | 0 | 1 | 2 | 4 | 1 | 1 | 0 |
| Overall Study | Other | 0 | 0 | 1 | 0 | 2 | 3 | 0 | 0 | 0 |
| Overall Study | Progressive Disease | 1 | 1 | 0 | 3 | 5 | 4 | 3 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 3 | 2 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Part 1B: PF-06952229 375mg + Enzalutamide | Part 1B: PF-06952229 250mg + Enzalutamide | Part 1A: PF-06952229 500mg Monotherapy | Part 1A: PF-06952229 375mg Monotherapy | Part 1A: PF-06952229 250mg Monotherapy | Part 1A: PF-06952229 150mg Monotherapy | Part 1A: PF-06952229 80mg Monotherapy | Part 1A: PF-06952229 40mg Monotherapy | Part 1A: PF-06952229 20mg Monotherapy |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 69.00 Years | 69.00 Years | 61.50 Years | 75.50 Years | 67.00 Years | 69.00 Years | 65.00 Years | 73.00 Years | 74.00 Years | 79.00 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 3 Participants | 4 Participants | 4 Participants | 14 Participants | 10 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not reported | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 40 Participants | 2 Participants | 3 Participants | 3 Participants | 14 Participants | 11 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 44 Participants | 3 Participants | 4 Participants | 4 Participants | 16 Participants | 10 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 5 | 0 / 13 | 0 / 17 | 0 / 4 | 0 / 4 | 0 / 3 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 1 / 1 | 4 / 5 | 13 / 13 | 16 / 17 | 4 / 4 | 4 / 4 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 3 / 5 | 3 / 13 | 5 / 17 | 0 / 4 | 0 / 4 | 0 / 3 |
Outcome results
Primary
Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment
First cycle DLTs were utilized to determine the max tolerated dose and future escalations or deescalations. Any of the following adverse events occurred in the first cycle of treatment which were clinically significant were classified as DLTs: Hematologic: Thrombocytopenia Grade 4 for \>=7 days, or Grade 3 or 4 associated with \>= Grade 2 clinically significant bleeding or requiring platelet transfusion; Neutropenia Grade 4 for \>=7 days; Grade\>=3 neutropenia with infection; Anemia Grade 4 or Grade 3 requiring blood transfusion. Nonhematologic: Grade\>=3 toxicities that were considered clinically significant; Alanine aminotransferase/aspartate aminotransferase\>3x the upper limit of normal (ULN) with bilirubin\>2x ULN without another explanation; Grade 3 nausea, vomiting or diarrhea that did not resolve within 4 days despite maximal supportive therapy. Nonhematologic and Non-Hepatic: Any toxicity caused\>= 2 weeks of dose delay or preventing participants from receiving 75% of study drug.
Time frame: Within 28 days of first dose or until the participant completed the first cycle of therapy if there were treatment delayed (on average 28 days).
Population: Population included all enrolled participants who received at least one dose of investigational product and included data evaluated for a minimum DLT observation period of 28 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 3 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With First-Cycle Dose-Limiting Toxicitys (DLTs) by Treatment | 0 Participants |
Primary
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Laboratory parameters included: hematology (hemoglobin, hematocrit, red blood cell, platelet and white blood cell count, neutrophils, eosinophils, monocytes, basophils and lymphocytes), chemistry (blood urea nitrogen, creatinine, sodium, potassium, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein and serum pregnancy test \[for all female participants\]) and urine (urine pregnancy test \[for all female participants\]). Clinical significance of laboratory parameters was determined at the investigator's discretion.
Time frame: Baseline up to 28 days after last dose of study treatment ( up to approximately 2 years)
Population: Population included all enrolled participants who received at least one dose of investigational product and with at least one observation of the given laboratory test during treatment period. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 1 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 1 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 1 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 1 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 1 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 1 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 1 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 1 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 1 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 1 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 1 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 2 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 4 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 1 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 3 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 1 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 3 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 1 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 2 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 2 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 3 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 2 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 2 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 6 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 2 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 4 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 3 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 8 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 8 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 13 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 9 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 4 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 4 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 2 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 2 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 2 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 1 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 2 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 2 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 3 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 7 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 3 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 4 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 2 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 1 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 1 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 3 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 2 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 2 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 2 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 2 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 3 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 3 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 1 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 2 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 4 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 3 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 3 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 2 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) > 1.5xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urea Nitrogen (mg/dL)> 1.3xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alkaline Phosphatase (U/L) > 3.0xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Time (sec) > 1.1xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Protein (Scalar)≥ 1 | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Monocytes (10^3/mm^3) > 1.2xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)< 0.8xLLN | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Phosphate (mg/dL)> 1.2xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Bilirubin (mg/dL)> 1.5xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Glucose (mg/dL)> 1.5xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | URINALYSIS: URINE Hemoglobin (Scalar)≥ 1 | 3 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Activated Partial Thromboplastin Time (sec) > 1.1xULN | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) < 0.9xLLN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Urate (mg/dL) > 1.2xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Basophils (10^3/mm^3) > 1.2xupper limit of normal (ULN) | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Magnesium (mg/dL)< 0.9xLLN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Sodium (mEq/L) < 0.95xLLN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Creatinine (mg/dL)> 1.3xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Prothrombin Intl. Normalized Ratio> 1.1xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Eosinophils (10^3/mm^3)> 1.2xULN | 2 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Lymphocytes (10^3/mm^3) < 0.8xLLN | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Hemoglobin (g/dL) < 0.8xlower limit of normal (LLN) | 2 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Potassium (mEq/L) > 1.1xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3)> 1.2xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Neutrophils (10^3/mm^3) < 0.8xLLN | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Chloride (mEq/L)< 0.9xLLN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | CLINICAL CHEMISTRY: Alanine Aminotransferase (U/L)> 3.0xULN | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) | HEMATOLOGY: Leukocytes (10^3/mm^3) < 0.6xLLN | 0 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (Treatment Related)
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 death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. Symptoms of infusion-related reactions (IRRs) may include, but were not limited to, fever, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria. Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Time frame: Baseline up to 28 days after last dose of study treatment ( up to approximately 2 years)
Population: Population included all enrolled participants who received at least one dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 1 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 0 Participants |
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 1 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 1 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 1 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 1 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 1 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 2 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 9 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 3 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 1 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 6 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 13 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 3 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 2 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 6 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 3 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 4 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 0 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 3 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 1 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 3 or 4 adverse events | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with serious adverse events | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued study drug due to AE and continue Study | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with adverse events | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with dose reduced or temporary discontinuation due to adverse events | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants discontinued from study due to adverse events | 1 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) | Participants with Maximum Grade 5 adverse events | 0 Participants |
Secondary
Apparent Clearance (CL/F) of PF-06952229 (Part 1A)
Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. CL/F = Dose/AUCinf for single dose; CL/F = Dose/AUCtau for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with advanced/metastatic tumors in PF-06952229 single agent dose escalation phase, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for CL/F. CL/F can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 9.850 liter per hour (L/hr) | — |
| Part 1A: PF-06952229 40mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 21.80 liter per hour (L/hr) | — |
| Part 1A: PF-06952229 80mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 22.30 liter per hour (L/hr) | — |
| Part 1A: PF-06952229 150mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 17.36 liter per hour (L/hr) | Geometric Coefficient of Variation 79 |
| Part 1A: PF-06952229 250mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 50.23 liter per hour (L/hr) | Geometric Coefficient of Variation 32 |
| Part 1A: PF-06952229 250mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 15.95 liter per hour (L/hr) | Geometric Coefficient of Variation 127 |
| Part 1A: PF-06952229 375mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 36.86 liter per hour (L/hr) | Geometric Coefficient of Variation 43 |
| Part 1A: PF-06952229 375mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 55.00 liter per hour (L/hr) | — |
| Part 1A: PF-06952229 375mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 19.49 liter per hour (L/hr) | Geometric Coefficient of Variation 92 |
| Part 1A: PF-06952229 500mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 29.04 liter per hour (L/hr) | Geometric Coefficient of Variation 132 |
| Part 1A: PF-06952229 500mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 27.10 liter per hour (L/hr) | — |
Secondary
Apparent Clearance (CL/F) of PF-06952229 (Part 1B)
Apparent Clearance After Oral Dose (CL/F) was defined as apparent clearance after oral dose on the last day of treatment period. CL/F = Dose/AUCinf for single dose; CL/F = Dose/AUCtau for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with mCRPC, conducted dose escalation of PF-06952229 in combination with enzalutamide, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for CL/F. CL/F can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 14.65 L/hr | Geometric Coefficient of Variation 0 |
| Part 1A: PF-06952229 20mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1B) | Cycle 1 Day 21 | 30.86 L/hr | Geometric Coefficient of Variation 26 |
| Part 1A: PF-06952229 20mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 49.06 L/hr | Geometric Coefficient of Variation 76 |
| Part 1A: PF-06952229 40mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 25.38 L/hr | Geometric Coefficient of Variation 62 |
| Part 1A: PF-06952229 40mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1B) | Cycle 1 Day 21 | 43.04 L/hr | Geometric Coefficient of Variation 41 |
| Part 1A: PF-06952229 40mg Monotherapy | Apparent Clearance (CL/F) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 60.39 L/hr | Geometric Coefficient of Variation 3 |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A)
Vz/F was defined as apparent volume of distribution. Vz/F = Dose / (AUCinf\* kel) for single dose; Vz/F = Dose / (AUCtau\* kel) for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. Kel was defined as terminal phase rate constant.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with advanced/metastatic tumors in PF-06952229 single agent dose escalation phase, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for Vz/F. Vz/F can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 40mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 139.0 liter (L) | — |
| Part 1A: PF-06952229 250mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 187.2 liter (L) | Geometric Coefficient of Variation 31 |
| Part 1A: PF-06952229 375mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 178.1 liter (L) | Geometric Coefficient of Variation 46 |
| Part 1A: PF-06952229 375mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 266.0 liter (L) | — |
| Part 1A: PF-06952229 375mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 287.0 liter (L) | — |
| Part 1A: PF-06952229 500mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 130.0 liter (L) | — |
| Part 1A: PF-06952229 500mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 665.0 liter (L) | — |
Secondary
Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1B)
Vz/F was defined as apparent volume of distribution. Vz/F = Dose / (AUCinf\* kel) for single dose; Vz/F = Dose / (AUCtau\* kel) for steady-state. AUCtau was defined as Area under the plasma concentration-time profile from time zero to time tau (τ), the dosing interval, where τ = 24 and 12 hours for QD and BID dosing, respectively. Kel was defined as terminal phase rate constant.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2
Population: Participants with mCRPC, conducted dose escalation of PF-06952229 in combination with enzalutamide, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for Vz/F. Vz/F can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 161.8 Liter | Geometric Coefficient of Variation 14 |
| Part 1A: PF-06952229 20mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 372.4 Liter | Geometric Coefficient of Variation 67 |
| Part 1A: PF-06952229 40mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 228.4 Liter | Geometric Coefficient of Variation 4 |
| Part 1A: PF-06952229 40mg Monotherapy | Apparent Volume of Distribution (Vz/F) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 408.7 Liter | Geometric Coefficient of Variation 11 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1A)
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2
Population: Participants with advanced/metastatic tumors in PF-06952229 single agent dose escalation phase, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for AUCinf. AUCinf can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 250mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 4974 ng*hr/mL | Geometric Coefficient of Variation 32 |
| Part 1A: PF-06952229 375mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 10160 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Part 1A: PF-06952229 375mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 6820 ng*hr/mL | — |
| Part 1A: PF-06952229 500mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 18500 ng*hr/mL | — |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1B)
AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2
Population: Participants with mCRPC, conducted dose escalation of PF-06952229 in combination with enzalutamide, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for AUCinf. AUCinf can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 17100 ng*hr/mL | Geometric Coefficient of Variation 1 |
| Part 1A: PF-06952229 20mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 5095 ng*hr/mL | Geometric Coefficient of Variation 75 |
| Part 1A: PF-06952229 40mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 14750 ng*hr/mL | Geometric Coefficient of Variation 61 |
| Part 1A: PF-06952229 40mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 6214 ng*hr/mL | Geometric Coefficient of Variation 3 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A)
AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2
Population: Participants with advanced/metastatic tumors in PF-06952229 single agent dose escalation phase, who had sufficient information to estimate at least 1 of the PK parameters of interest. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 785.0 nanograms*hour/milliliter (ng*hr/mL) | — |
| Part 1A: PF-06952229 20mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 466.0 nanograms*hour/milliliter (ng*hr/mL) | — |
| Part 1A: PF-06952229 40mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 1010 nanograms*hour/milliliter (ng*hr/mL) | — |
| Part 1A: PF-06952229 40mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 547.0 nanograms*hour/milliliter (ng*hr/mL) | — |
| Part 1A: PF-06952229 80mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 1190 nanograms*hour/milliliter (ng*hr/mL) | — |
| Part 1A: PF-06952229 80mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 508.0 nanograms*hour/milliliter (ng*hr/mL) | — |
| Part 1A: PF-06952229 150mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 2726 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 136 |
| Part 1A: PF-06952229 150mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 2035 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 42 |
| Part 1A: PF-06952229 250mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 5111 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 72 |
| Part 1A: PF-06952229 250mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 3130 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 329 |
| Part 1A: PF-06952229 375mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 8470 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 133 |
| Part 1A: PF-06952229 375mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 10050 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 97 |
| Part 1A: PF-06952229 500mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 6401 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 281 |
| Part 1A: PF-06952229 500mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 10540 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 159 |
Secondary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1B)
AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2
Population: Participants with mCRPC, conducted dose escalation of PF-06952229 in combination with enzalutamide, who had sufficient information to estimate at least 1 of the PK parameters of interest. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 16940 ng*hr/mL | Geometric Coefficient of Variation 24 |
| Part 1A: PF-06952229 20mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 6707 ng*hr/mL | Geometric Coefficient of Variation 85 |
| Part 1A: PF-06952229 40mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 13430 ng*hr/mL | Geometric Coefficient of Variation 34 |
| Part 1A: PF-06952229 40mg Monotherapy | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 5656 ng*hr/mL | Geometric Coefficient of Variation 11 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A)
Cmax was directly observed from data. Cmax was defined as maximum observed plasma concentration.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with advanced/metastatic tumors in PF-06952229 single agent dose escalation phase, who had sufficient information to estimate at least 1 of the pharmacokinetic (PK) parameters of interest. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 128.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 20mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 222.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 20mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 203.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 40mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 240.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 40mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 215.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 40mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 255.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 80mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 618.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 80mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 345.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 80mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 200.0 nanograms/milliliter (ng/mL) | — |
| Part 1A: PF-06952229 150mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 696.0 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 112 |
| Part 1A: PF-06952229 150mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 1050 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 85 |
| Part 1A: PF-06952229 150mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 509.7 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 173 |
| Part 1A: PF-06952229 250mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 1148 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 65 |
| Part 1A: PF-06952229 250mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 1787 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 131 |
| Part 1A: PF-06952229 250mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 1019 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 158 |
| Part 1A: PF-06952229 375mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 1876 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 95 |
| Part 1A: PF-06952229 375mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 1782 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 117 |
| Part 1A: PF-06952229 375mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 2727 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 98 |
| Part 1A: PF-06952229 500mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 2434 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 137 |
| Part 1A: PF-06952229 500mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 2917 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 88 |
| Part 1A: PF-06952229 500mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 1309 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 309 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B)
Cmax was directly observed from data. Cmax was defined as maximum observed plasma concentration.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with metastatic castration-resistant prostate cancer (mCRPC), conducted dose escalation of PF-06952229 in combination with enzalutamide, who had sufficient information to estimate at least 1 of the PK parameters of interest. Here, number analyzed signifies participant evaluable for each row
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 1619 ng/mL | Geometric Coefficient of Variation 45 |
| Part 1A: PF-06952229 20mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B) | Cycle 1 Day 21 | 1289 ng/mL | Geometric Coefficient of Variation 35 |
| Part 1A: PF-06952229 20mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 693.5 ng/mL | Geometric Coefficient of Variation 84 |
| Part 1A: PF-06952229 40mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 1462 ng/mL | Geometric Coefficient of Variation 21 |
| Part 1A: PF-06952229 40mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B) | Cycle 1 Day 21 | 1500 ng/mL | Geometric Coefficient of Variation 32 |
| Part 1A: PF-06952229 40mg Monotherapy | Maximum Observed Plasma Concentration (Cmax) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 960.3 ng/mL | Geometric Coefficient of Variation 13 |
Secondary
Number of Participants With Prostate Specific Antigen 50 (PSA50) Response
Prostate-specific antigen decline by more than 50% from baseline was analyzed. PSA partial response was defined as a ≥50% decline in PSA from Cycle 1 Day 1 (baseline) PSA value. This PSA decline much be confirmed to be sustained by a second PSA value obtained 4 or more weeks later.
Time frame: Baseline, Cycle 1 Day 1 (at the beginning of Cycle 1), and then every 3 cycles (each cycle is 28 days) until end of treatment (an average of 1 year)
Population: Population included all enrolled participants who had metastatic castration resistant prostate cancer (mCRPC)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
| Part 1A: PF-06952229 40mg Monotherapy | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
| Part 1A: PF-06952229 80mg Monotherapy | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
| Part 1A: PF-06952229 150mg Monotherapy | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
| Part 1A: PF-06952229 250mg Monotherapy | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
| Part 1A: PF-06952229 375mg Monotherapy | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 2 Participants |
| Part 1A: PF-06952229 500mg Monotherapy | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Number of Participants With Prostate Specific Antigen 50 (PSA50) Response | 0 Participants |
Secondary
Percentage of Participants With Objective Response
Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). Complete response was defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). All target lesions must be assessed. Partial response was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. The short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. All target lesions must be assessed.
Time frame: Baseline and every 8 to 12 weeks through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.
Population: Population included all enrolled participants who received at least 1 dose of investigational product, had baseline assessment and at least 1 post baseline assessment, disease progression, or death before the first tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Part 1A: PF-06952229 40mg Monotherapy | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Part 1A: PF-06952229 80mg Monotherapy | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Part 1A: PF-06952229 150mg Monotherapy | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Part 1A: PF-06952229 250mg Monotherapy | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Part 1A: PF-06952229 375mg Monotherapy | Percentage of Participants With Objective Response | 7.1 Percentage of participants |
| Part 1A: PF-06952229 500mg Monotherapy | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Part 1B: PF-06952229 250mg + Enzalutamide | Percentage of Participants With Objective Response | 0 Percentage of participants |
| Part 1B: PF-06952229 375mg + Enzalutamide | Percentage of Participants With Objective Response | 0 Percentage of participants |
Secondary
Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A)
Plasma terminal elimination half-life (T1/2) was the time measured for the plasma concentration to decrease by one half of its initial concentration.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with advanced/metastatic tumors in PF-06952229 single agent dose escalation phase, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for T1/2. T1/2 can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 40mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 4.410 Hour | — |
| Part 1A: PF-06952229 250mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 2.585 Hour | Standard Deviation 0.021213 |
| Part 1A: PF-06952229 375mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 2.550 Hour | — |
| Part 1A: PF-06952229 375mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 3.345 Hour | Standard Deviation 0.077782 |
| Part 1A: PF-06952229 375mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 3.350 Hour | — |
| Part 1A: PF-06952229 500mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 3.320 Hour | — |
| Part 1A: PF-06952229 500mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 3.670 Hour | — |
Secondary
Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1B)
Plasma terminal elimination half-life (T1/2) was the time measured for the plasma concentration to decrease by one half of its initial concentration.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 1 and cycle 2
Population: Participants with mCRPC, conducted dose escalation of PF-06952229 in combination with enzalutamide, who had sufficient information to estimate at least 1 of the PK parameters of interest and contributed to the summary statistics for T1/2. T1/2 can be evaluated only when a well characterized terminal phase was observed, which is defined as one with at least 3 data points, r\^2≥0.9, and AUCextrap%≤20. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 7.700 Hour | Standard Deviation 1.0041 |
| Part 1A: PF-06952229 20mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 5.265 Hour | Standard Deviation 0.33234 |
| Part 1A: PF-06952229 40mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 6.670 Hour | Standard Deviation 3.3658 |
| Part 1A: PF-06952229 40mg Monotherapy | Terminal Elimination Half-Life (T1/2) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 4.700 Hour | Standard Deviation 0.39598 |
Secondary
Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A)
Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 7 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with advanced/metastatic tumors in PF-06952229 single agent dose escalation phase, who had sufficient information to estimate at least 1 of the PK parameters of interest. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 0.967 hour (hr) |
| Part 1A: PF-06952229 20mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 2.10 hour (hr) |
| Part 1A: PF-06952229 20mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 3.95 hour (hr) |
| Part 1A: PF-06952229 40mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 6.08 hour (hr) |
| Part 1A: PF-06952229 40mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 3.83 hour (hr) |
| Part 1A: PF-06952229 40mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 2.05 hour (hr) |
| Part 1A: PF-06952229 80mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 2.00 hour (hr) |
| Part 1A: PF-06952229 80mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 2.18 hour (hr) |
| Part 1A: PF-06952229 80mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 5.52 hour (hr) |
| Part 1A: PF-06952229 150mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 5.99 hour (hr) |
| Part 1A: PF-06952229 150mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 2.15 hour (hr) |
| Part 1A: PF-06952229 150mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 1.51 hour (hr) |
| Part 1A: PF-06952229 250mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 2.17 hour (hr) |
| Part 1A: PF-06952229 250mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 2.00 hour (hr) |
| Part 1A: PF-06952229 250mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 4.14 hour (hr) |
| Part 1A: PF-06952229 375mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 2.03 hour (hr) |
| Part 1A: PF-06952229 375mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 5.02 hour (hr) |
| Part 1A: PF-06952229 375mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 1.92 hour (hr) |
| Part 1A: PF-06952229 500mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 2 Day 1 | 3.65 hour (hr) |
| Part 1A: PF-06952229 500mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 7 | 1.48 hour (hr) |
| Part 1A: PF-06952229 500mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1A) | Cycle 1 Day 1 | 1.97 hour (hr) |
Secondary
Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B)
Tmax was defined as time to maximum observed concentration. Observed directly from data as time of first occurrence.
Time frame: 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 and 21 of cycle 1, 0 (pre dose), 0.5, 1, 2, 4, 6 and 12 hours (post dose) on Day 1 of cycle 2.
Population: Participants with mCRPC, conducted dose escalation of PF-06952229 in combination with enzalutamide, who had sufficient information to estimate at least 1 of the PK parameters of interest. Here, number analyzed signifies participant evaluable for each row.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1A: PF-06952229 20mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 2.20 hour (hr) |
| Part 1A: PF-06952229 20mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B) | Cycle 1 Day 21 | 1.00 hour (hr) |
| Part 1A: PF-06952229 20mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 2.05 hour (hr) |
| Part 1A: PF-06952229 40mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B) | Cycle 1 Day 1 | 1.98 hour (hr) |
| Part 1A: PF-06952229 40mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B) | Cycle 1 Day 21 | 0.983 hour (hr) |
| Part 1A: PF-06952229 40mg Monotherapy | Time of Observed Maximum Plasma Concentration (Tmax) of PF-06952229 (Part 1B) | Cycle 2 Day 1 | 2.00 hour (hr) |