A Trial In Patients With Advanced Cancer And Leukemia

Any DLT event attributable to PF-03084014 during Cycle 1: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days or unable to deliver at least 80% of planned dose due to treatment-related toxicities; Grade 4 neutropenia \>7 days; febrile neutropenia; neutropenic infection; Grade \>=3 thrombocytopenia with bleeding

Time frame: Baseline to the end of Cycle 1 (Week 4)

Population: Solid tumor participants enrolled for dose-escalation who started treatment and who did not have first cycle major treatment deviations (including less than 80% of the planned dose of PF-03084014 in Cycle 1 for reasons other than treatment-related toxicities) were evaluable for DLTs.

Any DLT attributable to PF-03084014 at 1st Cycle: non-hematologic toxicities \>= Grade 3 despite optimal care; treatment delay \>=7 days; unable to deliver at least 80% of planned dose; absolute neutrophil count (ANC) \<1000/microliter (uL), or platelet count \<30,000/uL, or hemoglobin \<8 gram/deciliter (g/dL) in a bone marrow with \<5% blasts and no evidence of leukemia or abnormal dysplasia for \>42 days

Time frame: Baseline to the end of Cycle 1 (Week 4)

Population: T-ALL/LBL participants enrolled for dose-escalation who started treatment and who did not have first cycle major treatment deviations (including less than 80% of the planned dose of PF-03084014 in Cycle 1 for reasons other than treatment-related toxicities) were evaluable for DLTs.

Accumulation was calculated as AUCtau at steady state (Cycle 1 Day 21) divided by AUCtau after a single dose on Cycle 1 Day 1. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose), Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM.

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM

AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). CV is the coefficient of variation.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. Overall Number of Participants Analyzed (N) =number of participants evaluable for this outcome measure (OM).

AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM

AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval).

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: Solid tumor participants who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.

AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval).

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: Solid tumor participants who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.

AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Data for this outcome measure was planned to be analyzed for two arms only.

Time frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

Cavg was the average serum concentration at steady state. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM

Ribonucleic acid (RNA) was extracted from peripheral blood and used as a template to synthesize complementary deoxyribonucleic acid (cDNA). Gene expression in cDNA was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).

Time frame: Baseline (morning), Cycle 1 Days 8, 15 and 21 (morning, matched with the first PK sample of the particular day), Cycle 1 Day 21 (24, 48, and 120 hr post-dose) and at end of treatment (EOT)

Population: Pharmacodynamic biomarker analysis set. In both cases, it will comprise all participants enrolled in study having at least 1 biomarker assessment at baseline and at least 1 assessment after being treated. Here, N=participants evaluable for this OM. This OM was planned to be analyze for T-ALL/LBL arm only.

Notch intracellular domain (NICD) was to be measured in bone marrow monoculear cell (BMMC) cell pellets using a validated ELISA.

Time frame: Baseline, Cycle 1 Day 1 and Cycle 2 Day 1

Population: NICD analyses in bone marrow samples were not done because the number of bone marrow samples received was insufficient and because the analyses were not mandatory per protocol.

Notch intracellular domain (NICD) levels was measured in peripheral blood mononuclear cell (PBMC) pellets using a validated enzyme-linked immunosorbent assay (ELISA).

Time frame: Baseline, Cycle 1 Days 8 and 15 (pre-dose AM), Cycle 1 Day 21 (pre-dose AM and 24, 48 and 120 hr post-dose) and end of treatment (EOT).

Population: No data were reported for the results of NICD measurement in T-ALL/LBL participants because NICD levels fell below the limit of quantitation of the assay in most cases.

Ribonucleic acid (RNA) was extracted from peripheral blood and used as a template to synthesize complementary deoxyribonucleic acid (cDNA). Gene expression in cDNA was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).

Time frame: Baseline (morning), Cycle 1 Days 8 and 21 (pre-dose)

Population: Pharmacodynamic Biomarker analysis set was defined separately for T-ALL and advanced solid tumor malignancy participants. In both cases it will comprise all participants enrolled in study having at least one biomarker assessment at baseline and at least one assessment after being treated. Here, N signifies participants evaluable for this OM.

Gene expression analysis in tumor biopsies was done using cDNA prepared from RNA extracted from tumor biopsies. Gene expression was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Only Hes4 gene showed consistent down modulation across dosing cohorts (150 mg and 220 mg BID) and therefore results were reported for Hes4 only. Data for this outcome measure was planned to be analyzed for two arms only.

Time frame: Baseline, Cycle 1 Day 21 (-5 days)

Population: Pharmacodynamic Biomarker analysis set was defined separately for T-ALL and advanced solid tumor malignancy participants. In both cases it will comprise all participants enrolled in study having at least one biomarker assessment at baseline and at least one assessment after being treated. Here, N signifies participants evaluable for this OM.

Cmax was the maximum observed serum concentration. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant. CV is the coefficient of variation.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM.

Cmax was the maximum observed serum concentration.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: Solid tumor participants who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.

Cmax was the maximum observed serum concentration.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: Solid tumor participants who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.

Cmax was the maximum observed serum concentration. Data for this outcome measure was planned to be analyzed for two arms only.

Time frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. NE is not estimable.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM.

AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: Solid tumor participants who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states. Due to the limited number of evaluable participants (7 at 150 mg BID and 4 at 220 mg BID for Cmax) and a generally dose-proportional exposure (AUCtau and Cmax), data were combined for the 2 dose levels.

AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: Solid tumor participants who were enrolled in the food-effect sub-study, started treatment and had evaluable PK data under both fed and fasted states. Due to the limited number of evaluable participants (7 at 150 mg BID and 4 at 220 mg BID for Cmax) and a generally dose-proportional exposure (AUCtau and Cmax), data were combined for 2 dose levels.

AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Data for this outcome measure was planned to be analyzed for two arms only.

Time frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM.

Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: Participants who were enrolled in the food-effect sub-study, started treatment and had evaluable PK data under both fed and fasted states. Due to the limited number of evaluable participants (9 at 150 mg BID and 4 at 220 mg BID for Cmax) and a generally dose-proportional exposure (AUCtau and Cmax), data were combined for the 2 dose levels.

Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose).

Population: Solid tumor participants who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states. Due to the limited number of evaluable participants (9 at 150 mg BID and 4 at 220 mg BID for Cmax) and a generally dose-proportional exposure (AUCtau and Cmax), data were combined for the 2 dose levels.

Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Data for this outcome measure was planned to be analyzed for two arms only.

Time frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

Time from the first documentation of OR to objective disease progression or death due to any cause. DR was only calculated for participants with an OR. DR (months) was calculated as (date of first documentation of objective progression or death minus date of first documentation of PR or CR plus 1) divided by 30.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or -5 days) of every odd cycle or as clinically indicated, up to Cycle 9. Afterwards, assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months)

Population: Only solid tumor participants with an OR were analyzed; however, all these participants were censored as of the time of data cut-off on 09 January 2013. Of these 6 participants, 4 participants were still on study with 1 participant discontinued for non-compliance and the other 1 participant missing tumor assessment.

Cmax was the maximum observed serum concentration.

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this outcome measure (OM).

Cmin was the minimum serum concentration. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM

Parameters analyzed included: white blood cell (WBC) count plus differential, absolute (abs) neutrophil count, platelets, hemoglobin, sodium, potassium, bicarbonate, chloride, blood urea nitrogen, creatinine, glucose, uric acid, calcium, phosphate, magnesium, total protein, albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), partial prothrombin time/international normalized ratio (PTT/INR). Urinalysis: pH, specific gravity, protein, glucose, ketones, blood, leukocyte esterase, and nitrites. Pregnancy test: Serum or urine pregnancy test for women of childbearing potential. There were no changes in urine protein among the solid tumor and T-ALL/LBL participants that were clinically significant. Clinical significance was judged by the investigator.

Time frame: Baseline up to end of study (maximum of 84 months)

Population: All participants who received at least 1 dose of study medication.

Criteria for potentially important changes in ECG were defined as: maximum (max.) post-dose (post-baseline) time from electrocardiogram Q wave to the corresponding to electrical systole (QT interval) corrected for Fridericia's factor (QTcF), or QT interval corrected for Bazett's factor (QTcB): \<450, 450 -\<480, 480-\<500, and \>=500 msec. Maximum increase (inc.) from baseline in QTcF or QTcB: change (chg) \<30, 30\>=chg\<60, and chg \>=60 msec.

Time frame: Baseline up to end of study (maximum of 84 months)

Population: All participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence in a participant who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. An SAE was any untoward medical occurrence at any dose that: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect.

Time frame: Baseline up to end of study (maximum of 84 months)

Population: All participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE.

Time frame: Baseline up to end of study (maximum of 84 months)

Population: All participants who received at least 1 dose of study medication.

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of casual relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect.

Time frame: Baseline up to end of study (maximum of 84 months)

Population: All participants who received at least 1 dose of study medication.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE.

Time frame: Baseline up to end of study (maximum of 84 months)

Population: All participants who received at least 1 dose of study medication.

Objective response (OR) was defined as confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as \>=30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study \>=4 weeks after initial documentation of response.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (plus [+] or minus [-] 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles

Population: All solid tumor participants who received study treatment, had baseline assessments and at least 1 on study tumor assessment prior to any new anti-cancer therapies were considered evaluable for response.

OR was adapted from International Working Group Response Criteria for Acute Myeloid Leukemia (AML). The response categories of interest were CR, complete response with incomplete hematopoietic recovery (CRi), and PR. CR: ANC \>1500/microliter (uL), no circulating blasts. Platelets \>100,000/uL, \<5% marrow blast cells, no extramedullary disease, bone marrow cellularity \>20% with tri-lineage hematopoiesis and \<5% marrow blast cells, none of which were neoplastic; CRi: same as CR but ANC may be \>1500/uL or platelet count \>100,000/uL, no requirement on bone marrow cellularity; PR: same as CR but bone marrow with \>= 50% reduction of leukemia blast cells and an absolute blast count between 5% and 25%.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months)

Population: All T-ALL/LBL participants who received at least 1 dose of study medication.

PBR was the maximum percentage of peripheral blast count reduction for each participant who received at least one dose of study medication. PBR was derived by the Sponsor from percentage of peripheral blood Blast Count reported by sites.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months)

Population: Due to halting of T-AA/LBL participants enrollment and limited number of evaluable participants, data for PBR was not collected.

PFS was defined as the time from Cycle 1 Day 1 to date of first documentation of progression or death due to any cause. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, unequivocal progression of non-target disease, or the appearance of new lesions. PFS (months) was calculated as (the first event date minus the date of first dose of study medication plus 1) divided by 30.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles (up to maximum of 84 months)

Population: All solid tumor participants who received at least 1 dose of study medication.

The RFS of CR was defined as the time from the date of first attaining CR to the date of relapse or death from any cause, whichever occurred first. Similarly, the RFS of CR + CRi (or RFS of CR + CRi + PR) was defined as the time from the date of first attaining CR + CRi (or CR + CRi + PR) to the date of relapse or death from any cause, whichever occurred first.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9 (up to maximum of 84 months)

Population: Due to halting of T-AA/LBL participants enrollment and limited number of evaluable participants, data for RFS was not collected.

Serum decay half-life (t1/2) is the time measured for the serum concentration to decrease by one half. Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM

Tmax was the time to reach maximum serum concentration (Cmax).

Time frame: Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

Tmax was the time to reach maximum serum concentration (Cmax). Cycle 1 Day 21 PK parameter summaries are presented only for participants who were considered to be dose compliant.

Time frame: Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)

Population: All participants who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of participants evaluable for this OM

Time from Cycle 1 Day 1 to first documentation of disease progression. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, uneuivocal progression of non-target disease, or the appearance of new lesions. TTP (months) was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.

Time frame: Baseline until first documented objective progression (up to maximum of 84 months)

Population: All solid tumor participants who received at least 1 dose of study medication.

Tmax was the time to reach maximum serum concentration (Cmax). Data for this outcome measure was planned to be analyzed for two arms only.

Time frame: Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)

Population: All treated participants who had at least 1 of the PK parameters of interest. N=number of participants evaluable for this OM.

Time to response (TTR) was only defined for participants with an objective response (OR). TTR (months) was calculated as (date of first documentation of PR or CR minus date of first dose of study medication plus 1) divided by 30.

Time frame: Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or -5 days) of every odd cycle or as clinically indicated, up to Cycle 9. Afterwards, assessed on Day 1 (+ or -5 days) every 4 cycles.

Population: Only solid tumor participants with an OR were analyzed.