Trial Outcomes & Findings for Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients (NCT NCT02732938)

Last Updated: 2019-02-04

Results Overview

DLT: Any of the following events occurred in the first treatment cycle and was attributed to the combination of PF-04136309 with nab-paclitaxel and gemcitabine where relationship with the combination could not be ruled out. Hematologic: Grade (Gr) 4 neutropenia lasting more than (\>)5 days; febrile neutropenia; Gr≥3 neutropenic infection; Gr≥3 thrombocytopenia with Gr≥2 bleeding; Gr4 thrombocytopenia. Non-Hematologic: Gr3 toxicities (except: nausea and vomiting responding to prophylaxis and/or treatment and lasting less than (\<)7 days from each chemotherapy infusion period; diarrhea responding to treatment and lasting \<7 days; Gr3 QTc prolongation \[QTc \>500 milliseconds\] \[a DLT only if persisting after correction of any reversible causes\]; Gr3 aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) increase lasting less than or equal to (≤)7 days); all Gr4 toxicities; delay of \>2 weeks in receiving the next scheduled cycle due to persisting treatment-related toxicities.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Day 1 to Day 28

Results posted on

2019-02-04

Participant Flow

Phase 2 part of the study was not conducted due to early termination.

Participant milestones

Participant milestones
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Overall Study STARTED	4	18
Overall Study Received Treatment	4	17
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	4	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Overall Study Death	0	11
Overall Study Randomized but did not receive treatment	0	1
Overall Study Refused further follow-up	1	0
Overall Study Study terminated by sponsor	3	6

Baseline Characteristics

Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Total n=21 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	10 Participants n=7 Participants	12 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	61.3 years STANDARD_DEVIATION 10.2 • n=5 Participants	61.9 years STANDARD_DEVIATION 8.9 • n=7 Participants	61.8 years STANDARD_DEVIATION 8.9 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	15 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 28

Population: All Phase 1b enrolled participants who received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Number of Participants With Dose-Limiting Toxicities (DLTs) [Phase 1b]	1 Participants	3 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All Phase 1b enrolled participants who received at least 1 dose of study treatment.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening experience (immediate risk of dying); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Phase 1b] Treatment-emergent AE (all causality)	4 Participants	17 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Phase 1b] Treatment-emergent AE (PF-04136309 related)	3 Participants	16 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Phase 1b] Treatment-emergent SAE (all causality)	3 Participants	11 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Phase 1b] Treatment-emergent SAE (PF-04136309 related)	2 Participants	4 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All Phase 1b enrolled participants who received at least 1 dose of study treatment.

Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study treatment. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Phase 1b] Grade 1	0 Participants	0 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Phase 1b] Grade 2	0 Participants	1 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Phase 1b] Grade 3	4 Participants	12 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Phase 1b] Grade 4	0 Participants	3 Participants
Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Phase 1b] Grade 5	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All Phase 1b enrolled participants who received at least 1 dose of study treatment.

Following parameters were analyzed for hematology laboratory test: hemoglobin, hematocrit, red blood cell (RBC) count, mean corpuscular volume (MCV); mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet count, white blood cell (WBC) count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Anemia, Grade 1	1 Participants	5 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Anemia, Grade 2	3 Participants	8 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Anemia, Grade 3	0 Participants	4 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Lymphocyte count increased, Grade 2	0 Participants	1 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Lymphopenia, Grade 1	1 Participants	3 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Lymphopenia, Grade 2	2 Participants	3 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Lymphopenia, Grade 3	1 Participants	8 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Neutrophils (absolute), Grade 1	0 Participants	1 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Neutrophils (absolute), Grade 2	0 Participants	5 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Neutrophils (absolute), Grade 3	3 Participants	2 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Neutrophils (absolute), Grade 4	0 Participants	1 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Platelets, Grade 1	3 Participants	10 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] Platelets, Grade 2	1 Participants	2 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] WBC, Grade 1	0 Participants	2 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] WBC, Grade 2	0 Participants	5 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] WBC, Grade 3	3 Participants	2 Participants
Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] WBC, Grade 4	0 Participants	1 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All Phase 1b enrolled participants who received at least 1 dose of study treatment. GGT was an additional test for potential Hy's law. Only 1 participant in the PF-04136309 500 mg BID + Nab-paclitaxel + Gemcitabine treatment group was tested for GGT.

Following parameters were analyzed for chemistry laboratory test: blood urea nitrogen (BUN), creatinine, glucose (fasting), calcium, sodium, potassium, chloride, total bicarbonate, AST, ALT, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, Magnesium, phosphorous or phosphate. For potential Hy's Law cases, in addition to repeating AST and ALT, laboratory tests should have included albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase (GGT), prothrombin time / international normalized ratio (PT/INR), alkaline phosphatase, total bile acids, and acetaminophen drug and/or protein adduct levels. Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypoglycemia, Grade 2	0 Participants	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypokalemia, Grade 1	1 Participants	3 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypokalemia, Grade 3	0 Participants	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypomagnesemia, Grade 1	1 Participants	5 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hyponatremia, Grade 1	0 Participants	7 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hyponatremia, Grade 3	0 Participants	3 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypophosphatemia, Grade 2	0 Participants	3 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypophosphatemia, Grade 3	0 Participants	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] ALT, Grade 1	1 Participants	8 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] ALT, Grade 2	2 Participants	3 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] ALT, Grade 3	1 Participants	4 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] ALT, Grade 4	0 Participants	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Alkaline phosphatase, Grade 1	2 Participants	7 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Alkaline phosphatase, Grade 2	1 Participants	5 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Alkaline phosphatase, Grade 3	0 Participants	2 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] AST, Grade 1	2 Participants	8 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] AST, Grade 2	1 Participants	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] AST, Grade 3	1 Participants	5 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Bilirubin (total), Grade 1	0 Participants	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Bilirubin (total), Grade 2	0 Participants	3 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Bilirubin (total), Grade 3	0 Participants	2 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Creatinine, Grade 1	4 Participants	9 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Creatinine, Grade 2	0 Participants	2 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] GGT, Grade 1	—	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hyperglycemia, Grade 1	2 Participants	6 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hyperglycemia, Grade 2	2 Participants	6 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hyperglycemia, Grade 3	0 Participants	5 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hyperkalemia, Grade 1	0 Participants	2 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypermagnesemia, Grade 1	0 Participants	1 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypoalbuminemia, Grade 1	0 Participants	8 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypoalbuminemia, Grade 2	1 Participants	6 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypocalcemia, Grade 1	2 Participants	6 Participants
Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] Hypocalcemia, Grade 2	0 Participants	2 Participants

PRIMARY outcome

Timeframe: 1 year

Population: All Phase 1b participants who received at least 1 dose of study treatment and had at least 1 post-dose urinalysis laboratory test.

Following parameters were analyzed for urinalysis laboratory test: pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy (only if urine dipstick was positive for blood, protein, nitrites or leukocyte esterase), urine dipstick for urine protein (if positive collected 24 hour and microscopic \[reflex testing\]), urine dipstick for urine blood (if positive collected a microscopic \[reflex testing\]). Laboratory abnormalities were graded per NCI CTCAE version 4.03 and those with at least 1 participant are presented here.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=16 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Number of Participants With Urinalysis Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b]	1 Participants	0 Participants

PRIMARY outcome

Timeframe: 1 year

Population: No data to report as Phase 2 part was not conducted.

PFS was defined as the time from randomization to first documentation of objective tumor progression or to death due to any cause, whichever occurred first.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 1 Day 15 pre-dose (within 30 minutes), and 0.5, 1, 2, 3, 4, and 6 hours after the morning dose; Cycle 1 Day 16 pre-dose (within 30 minutes; as the 12-hour sample for evening dose on Day 15)

Population: "Number of participants analyzed" represents all Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had Cmax data; "Number analyzed" represents the number of such participants for each category.

Cmax of PF-04136309 was observed directly from data. This outcome measure reports individual values for the participants in the Phase 1b PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine treatment group as summary statistics were not generated when fewer than 3 participants had reportable data.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=2 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Maximum Observed Plasma Concentration (Cmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 1	3390 nanograms per milliliter (ng/mL)	—
PF-04136309 Maximum Observed Plasma Concentration (Cmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 2	2950 nanograms per milliliter (ng/mL)	—

SECONDARY outcome

Population: All Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had Cmax data.

Cmax of PF-04136309 was observed directly from data. This outcome measure reports summary statistics for the participants in the Phase 1b PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine treatment group. Arithmetic coefficient of variation (CV) was the intended method of dispersion for reporting but system only has geometric CV option, hence geometric CV data were reported for this parameter.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=13 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Maximum Observed Plasma Concentration (Cmax) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]	1276 ng/mL Geometric Coefficient of Variation 52	—

SECONDARY outcome

Population: "Number of participants analyzed" represents all Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had Tmax data; "Number analyzed" represents the number of such participants for each category.

Tmax of PF-04136309 was observed directly from data as time of first occurrence. This outcome measure reports individual values for the participants in the Phase 1b PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine treatment group as summary statistics were not generated when fewer than 3 participants had reportable data.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=2 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Time to Reach Maximum Observed Plasma Concentration (Tmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 1	1.00 hours (hr)	—
PF-04136309 Time to Reach Maximum Observed Plasma Concentration (Tmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 2	3.02 hours (hr)	—

SECONDARY outcome

Population: All Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had Tmax data.

Tmax of PF-04136309 was observed directly from data as time of first occurrence. This outcome measure reports summary statistics for the participants in the Phase 1b PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine treatment group.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=13 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Time to Reach Maximum Observed Plasma Concentration (Tmax) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]	1.42 hours (hr) Interval 0.5 to 5.95	—

SECONDARY outcome

Population: "Number of participants analyzed" represents all Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had AUCtau data; "Number analyzed" represents the number of such participants for each category.

The dosing interval was 12 hours for PF-04136309 BID dosing. AUCtau was determined by linear/log trapezoidal method. This outcome measure reports individual values for the participants in the Phase 1b PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine treatment group as summary statistics were not generated when fewer than 3 participants had reportable data.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=2 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 1	15700 nanogramhour/milliliter (nghr/mL)	—
PF-04136309 Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 2	10600 nanogramhour/milliliter (nghr/mL)	—

SECONDARY outcome

Population: All Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had AUCtau data.

The dosing interval was 12 hours for PF-04136309 BID dosing. AUCtau was determined by linear/log trapezoidal method. This outcome measure reports summary statistics for the participants in the Phase 1b PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine treatment group. Arithmetic CV was the intended method of dispersion for reporting but system only has geometric CV option, hence geometric CV data were reported for this parameter.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=13 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]	5873 ng*hr/mL Geometric Coefficient of Variation 36	—

SECONDARY outcome

Population: "Number of participants analyzed" represents all Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had Cmin data; "Number analyzed" represents the number of such participants for each category.

Cmin of PF-04136309 was observed directly from data. This outcome measure reports individual values for the participants in the Phase 1b PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine treatment group as summary statistics were not generated when fewer than 3 participants had reportable data.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=2 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Minimum Observed Plasma Concentration (Cmin) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 1	436 ng/mL	—
PF-04136309 Minimum Observed Plasma Concentration (Cmin) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 2	0 ng/mL	—

SECONDARY outcome

Population: All Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had Cmin data.

Cmin of PF-04136309 was observed directly from data. This outcome measure reports summary statistics for the participants in the Phase 1b PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine treatment group.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=13 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Minimum Observed Plasma Concentration (Cmin) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]	72.34 ng/mL Geometric Coefficient of Variation NA NA for geometric coefficient of variation as there were participants with a zero value (ie, Cmin below the limit of quantification).	—

SECONDARY outcome

Population: "Number of participants analyzed" represents all Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had CL/F data; "Number analyzed" represents the number of such participants for each category.

CL/F was determined by Dose/AUCtau. AUCtau is the area under the curve from time 0 to end of dosing interval. This outcome measure reports individual values for the participants in the Phase 1b PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine treatment group as summary statistics were not generated when fewer than 3 participants had reportable data.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=2 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Apparent Oral Clearance (CL/F) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 1	47.8 Liters per hour (L/hr)	—
PF-04136309 Apparent Oral Clearance (CL/F) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] Individual value for Participant 2	70.5 Liters per hour (L/hr)	—

SECONDARY outcome

Population: All Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had CL/F data.

CL/F was determined by Dose/AUCtau. AUCtau is the area under the curve from time 0 to end of dosing interval. This outcome measure reports summary statistics for the participants in the Phase 1b PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine treatment group. Arithmetic CV was the intended method of dispersion for reporting but system only has geometric CV option, hence geometric CV data were reported for this parameter.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=13 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Apparent Oral Clearance (CL/F) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]	85.09 Liters per hour (L/hr) Geometric Coefficient of Variation 36	—

SECONDARY outcome

Population: All Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had t1/2 data.

t1/2 was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log linear decline were used in the regression.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=1 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=10 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Plasma Decay Half-Life (t1/2) for Cycle 1 Day 15 [Phase 1b]	1.18 hours (hr) Standard Deviation NA NA for standard deviation as only 1 participant had data for t1/2.	3.41 hours (hr) Standard Deviation 0.996

SECONDARY outcome

Population: All Phase 1b participants who received planned treatments on Cycle 1 Day 15 and had Vz/F data.

Vz/F was determined by Dose/(AUCtau×kel). AUCtau is the area under the curve from time 0 to end of dosing interval and kel is the terminal phase rate constant.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=1 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=10 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
PF-04136309 Apparent Volume of Distribution (Vz/F) for Cycle 1 Day 15 [Phase 1b]	120 Liters (L) Geometric Coefficient of Variation NA NA for geometric coefficient of variation as only 1 participant had data for Vz/F.	398.3 Liters (L) Geometric Coefficient of Variation NA NA for geometric coefficient of variation as there were missing values for Vz/F.

OTHER_PRE_SPECIFIED outcome

Timeframe: 1 year

Population: All the Phase 1b treated participants with measurable disease baseline assessment.

Outcome measures

Outcome measures
Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 Participants PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Objective Response Rate (ORR) [Phase 1b]	0 Percentage of Participants Interval 0.0 to 60.2	29.4 Percentage of Participants Interval 10.3 to 56.0

Adverse Events

Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine

Serious events: 11 serious events

Other events: 17 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine n=4 participants at risk PF-04136309 (formulated 125 mg tablets) was administered orally at 750 mg twice-daily (BID) for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an intravenous (IV) infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine n=17 participants at risk PF-04136309 (formulated 125 mg tablets) was administered orally at 500 mg BID for 28-day cycles. Nab-paclitaxel (125 mg/m2) was administered as an IV infusion on Days 1, 8 and 15 followed by 1 week of no treatment in 28-day cycles. Gemcitabine (1000 mg/m2) was administered as an IV infusion immediately after nab-paclitaxel, on Days 1, 8 and 15 followed by 1 week off treatment for 28-day cycles.
Eye disorders Episcleritis	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Gastrointestinal disorders Abdominal pain	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	11.8% 2/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Gastrointestinal disorders Gastrooesophageal reflux disease	25.0% 1/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	0.00% 0/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
General disorders Chest pain	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
General disorders Pyrexia	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	11.8% 2/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Infections and infestations Biliary sepsis	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Infections and infestations Cellulitis	25.0% 1/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	0.00% 0/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Infections and infestations Klebsiella bacteraemia	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Infections and infestations Liver abscess	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Infections and infestations Pneumonia	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Infections and infestations Sepsis	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Metabolism and nutrition disorders Decreased appetite	25.0% 1/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	0.00% 0/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Nervous system disorders Cognitive disorder	25.0% 1/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	0.00% 0/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	5.9% 1/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	17.6% 3/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).
Skin and subcutaneous tissue disorders Rash	25.0% 1/4 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).	0.00% 0/17 • AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year). Survival status was collected every 3 months after treatment discontinuation. A total of 11 deaths were reported, 1 of which was within AE reporting time frame (within 28 days after last dose of study treatment) and 10 of which were after AE reporting time frame (after 28 days following last dose of study treatment).