CCR2i: Ph1b/2 Study of PF-04136309 in Combination With Gem/Nab-P in First-line Metastatic Pancreatic Patients

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02732938
• Collaborator: (none)
• Enrollment: 22
• Locations: 18
• Arm: 1
• Actual Duration (Months): 17.2
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this Phase 1b/2 study is to evaluate the safety and tolerability of PF-04136309 in combination with nab-paclitaxel and gemcitabine, characterize the dose-limiting toxicities (DLTs) and overall safety profile of escalated doses of PF-04136309 and the associated schedule, determine the maximum tolerated dose (MTD), and to assess the enhancement of efficacy of PF-04136309 in combination with nab-paclitaxel and gemcitabine versus nab-paclitaxel + gemcitabine + placebo in terms of Progression Free Survival.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Pancreatic Ductal Adenocarcinoma	Drug: PF-04136309; Drug: Nab-paclitaxel; Drug: Gemcitabine	Phase 2

Detailed Description

The study has 2 parts:

Phase 1b (dose-finding cohorts) will be open label as patients will receive ascending doses of PF-04136309 in combination with nab-paclitaxel + gemcitabine. The observation period for dose-limiting toxicities (DLTs) will be from Day 1 to Day 28. Pharmacokinetic (PK) and pharmacodynamic (PD) properties of PF-04136309 will also be assessed. The criteria for dose escalation will be based on a modified toxicity probability interval (mTPI) method. After evaluating the safety and other results (eg, PK) from patients enrolled in the dose escalation cohorts, a dose level will be selected to be further evaluated as the Recommended Phase 2 Dose (RP2D). A minimum of 6 patients, up to 12 patients, will be treated at this dose level to establish it as the RP2D. To further evaluate safety and pharmacodynamics, the number of patients enrolled during this part of the study (Phase 1b) may be N up to 20. The study will stop if all PF-04136309 doses explored appear to be overly toxic.

Phase 2 randomized double blinded placebo control. Approximately 92 patients will be randomized 1:1 to receive the RP2D of PF-04136309 in combination with nab-paclitaxel + gemcitabine (ARM A; n=46) versus nab-paclitaxel + gemcitabine + placebo (ARM B; n=46). The primary objective will be the enhancement of efficacy in terms of PFS.

Patients will be treated as long as they are clinically benefiting from investigational product without unacceptable toxicity, objective disease progression, or withdrawal of consent.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PHASE 1B/2 STUDY OF PF-04136309 IN COMBINATION WITH GEMCITABINE AND NAB-PACLITAXEL IN PATIENTS WITH PREVIOUSLY UNTREATED METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
• Actual Study Start Date: May 4, 2016
• Actual Primary Completion Date: Sep 15, 2017
• Actual Study Completion Date: Oct 10, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-04136309 + Nab-p + Gem PF-04136309 oral dosing Nab-paclitaxel IV dosing Gemcitabine IV dosing	Drug: PF-04136309; PF-04136309 oral dosing; Drug: Nab-paclitaxel; Nab-paclitaxel IV dosing; Other Names: Abraxane ; Drug: Gemcitabine; Gemcitabine IV dosing; Other Names: Gemzar

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose-Limiting Toxicities (DLTs) [Phase 1b] [Day 1 to Day 28]

   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.

2. Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Phase 1b] [1 year]

   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.

3. Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Phase 1b] [1 year]

   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.

4. Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b] [1 year]

   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.

5. Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] [1 year]

   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.

6. Number of Participants With Urinalysis Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b] [1 year]

   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.

7. Progression Free Survival (PFS) [Phase 2] [1 year]

   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.

Secondary Outcome Measures

1. PF-04136309 Maximum Observed Plasma Concentration (Cmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] [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)]

   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.

2. PF-04136309 Maximum Observed Plasma Concentration (Cmax) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b] [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)]

   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.

3. PF-04136309 Time to Reach Maximum Observed Plasma Concentration (Tmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] [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)]

   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.

4. PF-04136309 Time to Reach Maximum Observed Plasma Concentration (Tmax) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b] [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)]

   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.

5. 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] [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)]

   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.

6. 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] [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)]

   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.

7. PF-04136309 Minimum Observed Plasma Concentration (Cmin) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] [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)]

   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.

8. PF-04136309 Minimum Observed Plasma Concentration (Cmin) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b] [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)]

   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.

9. PF-04136309 Apparent Oral Clearance (CL/F) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b] [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)]

   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.

10. PF-04136309 Apparent Oral Clearance (CL/F) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b] [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)]

    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.

11. PF-04136309 Plasma Decay Half-Life (t1/2) for Cycle 1 Day 15 [Phase 1b] [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)]

    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.

12. PF-04136309 Apparent Volume of Distribution (Vz/F) for Cycle 1 Day 15 [Phase 1b] [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)]

    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.

13. Ex Vivo Inhibition of Chemokine Ligand 2 (CCL2)-Induced Extracellular Signal Regulated Kinase (ERK) Phosphorylation in the Peripheral Blood [Phase 1b] [Cycle 1 Day 1 pre-dose, 2 and 6 hours post-dose, and 12 hours (pre-second BID dose-optional collection); Cycle 1 Days 2, 3 and 4 pre-dose]

    A drop in the CCL2-induced ERK kinase phosphorylation (pERK) biomarker level indicates target engagement (TE).

14. Number of Participants With Overall Survival (OS) [Phase 2] [Up to approximately 13.5 months]

    OS was defined as the time from date of randomization to date of death due to any cause. For participants not expiring, their survival times were to be censored at the last date they were known to be alive. Participants lacking data beyond the day of randomization were to have their survival times censored at the date of randomization with duration of 1 day.

15. Number of Participants With Treatment-Emergent Adverse Events (AEs) [Phase 2] [Up to approximately 1 year]

    An AE was any untoward medical occurrence in a participant administered a product or medical device 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.

16. Number of Participants With Laboratory Abnormalities by Severity [Phase 2] [Up to approximately 1 year]

    Hematology, chemistry, and urinalysis laboratory parameters were to be analyzed and graded by NCI CTCAE version 4.03.

17. Objective Response Rate (ORR) [Phase 2] [Up to approximately 1 year]

    ORR was defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1, relative to all randomized participants who had baseline measurable disease. Confirmed responses were those that persisted on repeat imaging study ≥4 weeks after initial documentation of response.

18. Duration of Objective Response (DR) [Phase 2] [Up to approximately 1 year]

    DR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. DR data were to be censored on the day following the date of the last on treatment (including 28 day follow-up period after last dose) tumor assessment documenting absence of progressive disease for participants who did not have objective tumor progression and who did not die due to any cause while on treatment or who were given anti-tumor treatment other than the study treatment prior to observing objective tumor progression. Participants who achieved a PR and then a CR were to have times calculated using the date of the PR as the first day. DR was only to be calculated for the subgroup of participants with objective response.

19. Time to Progression (TTP) With the Double Combination PF-04136309 and Gemcitabine (Maintenance Therapy) After Interruption of Nab-paclitaxel [Phase 2] [Up to approximately 1 year]

    This type of TTP was defined as the time from interruption of nab-paclitaxel to the first documentation of objective tumor progression. This TTP was to be only calculated for the subgroup of participants who were treated with the maintenance therapy.

20. Trough PF-04136309 Concentrations [Phase 2] [Cycle 1 Day 1 pre-dose, Cycle 1 Days 2, 8 and 15 pre-dose; Day 1 of Cycle 2 and subsequent cycles pre-dose, and EOT visit]

    The minimum plasma concentration of PF-04136309.

21. Change From Baseline in Pharmacodynamic (PD) Markers in Metastatic Tumors and Bone Marrow [Phase 2] [Baseline, Cycle 1 Day 28 or Cycle 2 Day 28; EOT visit (optional) for CNB]

    Collections of core needle biopsy (CNB) from a metastatic site or fine-needle aspirate (FNA) from the primary tumor tissue were optional but at least 12 paired biopsies would have to be available and fully assessable in each treatment arm to allow the comparison.

22. Number of Participants With Peripheral Neurological Adverse Events [Phase 2] [Up to approximately 1 year]

    To evaluate the improvement of peripheral neurotoxicity induced by nab-paclitaxel by the addition of PF-04136309 to the combination therapy of nab-paclitaxel plus gemcitabine.

Other Outcome Measures

1. Objective Response Rate (ORR) [Phase 1b] [1 year]

   ORR was defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1, relative to all randomized participants who had baseline measurable disease. Confirmed responses were those that persisted on repeat imaging study ≥4 weeks after initial documentation of response.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Histologically or cytologically proven diagnosis of metastatic ductal adenocarcinoma of the pancreas.

2. All patients must provide a baseline tumor sample at registration. If an archival sample is not available, patients must have a metastatic biopsy collected at the screening visit.

3. Patient must have received no previous radiotherapy, surgery, chemotherapy or investigational therapy for the treatment of metastatic disease.

4. Measurable disease as per RECIST v. 1.1.

5. Resolved acute effects of any prior therapy to baseline severity or Grade ≤1 NCI CTCAE.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

7. Age ≥18 years.

8. Adequate Bone Marrow, Renal and liver Functions.

Exclusion Criteria

1. Patients with known symptomatic brain metastases requiring steroids.

2. Prior therapy with modulators of monocyte or TAM function.

3. Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks of registering for the current study and/or during study participation.

4. Diagnosis of any second malignancy within the last 3 years, except for adequately treated basal cell carcinoma, or squamous cell skin carcinoma or in situ cervical carcinoma.

5. Known hypersensitivity to nab-paclitaxel or to gemcitabine or to any of the excipients.

6. Any one of the following currently or in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack; symptomatic pulmonary embolism; congenital long QT syndrome, torsades de points, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation), right bundle branch block and left anterior hemiblock (bifascicular block), ongoing cardiac dysrhythmias of NCI CTCAE Grade >=2, atrial fibrillation of any grade, or QTc interval >470 msec at screening.

7. Concurrent administration of herbal preparations.

8. Use of oral anticoagulants. Use of subcutaneous anti coagulation is allowed. Concurrent use of potent or moderate inhibitors or inducers of CYP3A4 and/or CYP2C8.

9. Active and clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.

10. History of interstitial lung disease, or slowly progressive dyspnea and unproductive cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary hypersensitivity pneumonitis or multiple allergies.

11. Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior) or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry into this study.

12. Pregnant female patients; breastfeeding female patients; males patients with partners currently pregnant, male patients able to father children and female patients of childbearing potential who are unwilling or unable to use two (2) highly effective methods of contraception as outlined in this protocol for the duration of the study and for 28 days after last dose of PF-04136309, and for 6 months after last dose of nab-paclitaxel, gemcitabine, or both.

13. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10022
6	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
7	University of Rochester Cancer Center Pharmacy	Rochester	New York	United States	14642
8	University of Rochester Medical Center	Rochester	New York	United States	14642
9	Sampson Regional Medical Center	Clinton	North Carolina	United States	28328
10	Southeastern Medical Oncology Center	Clinton	North Carolina	United States	28328
11	Southeastern Medical Oncology Center	Goldsboro	North Carolina	United States	27534
12	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
13	Onslow Memorial Hospital	Jacksonville	North Carolina	United States	28546
14	Southeastern Medical Oncology Center	Jacksonville	North Carolina	United States	28546
15	Medical University of South Carolina	Charleston	South Carolina	United States	29425
16	MUSC Hollings Cancer Center	Charleston	South Carolina	United States	29425
17	MUSC Health East Cooper	Mount Pleasant	South Carolina	United States	29464
18	MUSC Health North Charleston	North Charleston	South Carolina	United States	29406

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Study Protocol - Sep 30, 2016
• Statistical Analysis Plan - Apr 8, 2016

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02732938
• Other Study ID Numbers: A9421018; 2015-003767-11
• First Posted: Apr 11, 2016
• Last Update Posted: Feb 4, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Pfizer: CCR2i, nab-paclitaxel, Abraxane, gemcitabine, pancreas
• Additional relevant MeSH terms: Adenocarcinoma; Gemcitabine; Paclitaxel

Study Results

Participant Flow

Pre-assignment Detail	Phase 2 part of the study was not conducted due to early termination.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	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.	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.	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Period Title: Overall Study
STARTED	4	18	0
Received Treatment	4	17	0
COMPLETED	0	0	0
NOT COMPLETED	4	18	0

Baseline Characteristics

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine	Total
Arm/Group Description	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.	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 of all reporting groups
Overall Participants	4	17	21
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 50%	10 58.8%	12 57.1%
>=65 years	2 50%	7 41.2%	9 42.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.3 (10.2)	61.9 (8.9)	61.8 (8.9)
Sex: Female, Male (Count of Participants)
Female	4 100%	6 35.3%	10 47.6%
Male	0 0%	11 64.7%	11 52.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 5.9%	1 4.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 5.9%	1 4.8%
White	4 100%	15 88.2%	19 90.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-Limiting Toxicities (DLTs) [Phase 1b]
Description	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.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	4	17
Count of Participants [Participants]	1 25%	3 17.6%

2. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) [Phase 1b]
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	4	17
Treatment-emergent AE (all causality)	4 100%	17 100%
Treatment-emergent AE (PF-04136309 related)	3 75%	16 94.1%
Treatment-emergent SAE (all causality)	3 75%	11 64.7%
Treatment-emergent SAE (PF-04136309 related)	2 50%	4 23.5%

3. Primary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) by Severity [Phase 1b]
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	4	17
Grade 1	0 0%	0 0%
Grade 2	0 0%	1 5.9%
Grade 3	4 100%	12 70.6%
Grade 4	0 0%	3 17.6%
Grade 5	0 0%	1 5.9%

4. Primary Outcome

Title	Number of Participants With Hematology Laboratory Abnormalities by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade [Phase 1b]
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	4	17
Anemia, Grade 1	1 25%	5 29.4%
Anemia, Grade 2	3 75%	8 47.1%
Anemia, Grade 3	0 0%	4 23.5%
Lymphocyte count increased, Grade 2	0 0%	1 5.9%
Lymphopenia, Grade 1	1 25%	3 17.6%
Lymphopenia, Grade 2	2 50%	3 17.6%
Lymphopenia, Grade 3	1 25%	8 47.1%
Neutrophils (absolute), Grade 1	0 0%	1 5.9%
Neutrophils (absolute), Grade 2	0 0%	5 29.4%
Neutrophils (absolute), Grade 3	3 75%	2 11.8%
Neutrophils (absolute), Grade 4	0 0%	1 5.9%
Platelets, Grade 1	3 75%	10 58.8%
Platelets, Grade 2	1 25%	2 11.8%
WBC, Grade 1	0 0%	2 11.8%
WBC, Grade 2	0 0%	5 29.4%
WBC, Grade 3	3 75%	2 11.8%
WBC, Grade 4	0 0%	1 5.9%

5. Primary Outcome

Title	Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b]
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	4	17
ALT, Grade 1	1 25%	8 47.1%
ALT, Grade 2	2 50%	3 17.6%
ALT, Grade 3	1 25%	4 23.5%
ALT, Grade 4	0 0%	1 5.9%
Alkaline phosphatase, Grade 1	2 50%	7 41.2%
Alkaline phosphatase, Grade 2	1 25%	5 29.4%
Alkaline phosphatase, Grade 3	0 0%	2 11.8%
AST, Grade 1	2 50%	8 47.1%
AST, Grade 2	1 25%	1 5.9%
AST, Grade 3	1 25%	5 29.4%
Bilirubin (total), Grade 1	0 0%	1 5.9%
Bilirubin (total), Grade 2	0 0%	3 17.6%
Bilirubin (total), Grade 3	0 0%	2 11.8%
Creatinine, Grade 1	4 100%	9 52.9%
Creatinine, Grade 2	0 0%	2 11.8%
GGT, Grade 1	1 25%
Hyperglycemia, Grade 1	2 50%	6 35.3%
Hyperglycemia, Grade 2	2 50%	6 35.3%
Hyperglycemia, Grade 3	0 0%	5 29.4%
Hyperkalemia, Grade 1	0 0%	2 11.8%
Hypermagnesemia, Grade 1	0 0%	1 5.9%
Hypoalbuminemia, Grade 1	0 0%	8 47.1%
Hypoalbuminemia, Grade 2	1 25%	6 35.3%
Hypocalcemia, Grade 1	2 50%	6 35.3%
Hypocalcemia, Grade 2	0 0%	2 11.8%
Hypoglycemia, Grade 2	0 0%	1 5.9%
Hypokalemia, Grade 1	1 25%	3 17.6%
Hypokalemia, Grade 3	0 0%	1 5.9%
Hypomagnesemia, Grade 1	1 25%	5 29.4%
Hyponatremia, Grade 1	0 0%	7 41.2%
Hyponatremia, Grade 3	0 0%	3 17.6%
Hypophosphatemia, Grade 2	0 0%	3 17.6%
Hypophosphatemia, Grade 3	0 0%	1 5.9%

6. Primary Outcome

Title	Number of Participants With Urinalysis Laboratory Abnormalities by Maximum NCI CTCAE Grade [Phase 1b]
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	4	16
Count of Participants [Participants]	1 25%	0 0%

7. Primary Outcome

Title	Progression Free Survival (PFS) [Phase 2]
Description	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.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

8. Secondary Outcome

Title	PF-04136309 Maximum Observed Plasma Concentration (Cmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

"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.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	2
Individual value for Participant 1	3390
Individual value for Participant 2	2950

9. Secondary Outcome

Title	PF-04136309 Maximum Observed Plasma Concentration (Cmax) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1276 (52)

10. Secondary Outcome

Title	PF-04136309 Time to Reach Maximum Observed Plasma Concentration (Tmax) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

"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.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	2
Individual value for Participant 1	1.00
Individual value for Participant 2	3.02

11. Secondary Outcome

Title	PF-04136309 Time to Reach Maximum Observed Plasma Concentration (Tmax) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	13
Median (Full Range) [hours (hr)]	1.42

12. Secondary Outcome

Title	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]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

"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.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	2
Individual value for Participant 1	15700
Individual value for Participant 2	10600

13. Secondary Outcome

Title	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]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	13
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	5873 (36)

14. Secondary Outcome

Title	PF-04136309 Minimum Observed Plasma Concentration (Cmin) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

"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.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	2
Individual value for Participant 1	436
Individual value for Participant 2	0

15. Secondary Outcome

Title	PF-04136309 Minimum Observed Plasma Concentration (Cmin) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	72.34 (NA)

16. Secondary Outcome

Title	PF-04136309 Apparent Oral Clearance (CL/F) for Cycle 1 Day 15 in the 750 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

"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.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	2
Individual value for Participant 1	47.8
Individual value for Participant 2	70.5

17. Secondary Outcome

Title	PF-04136309 Apparent Oral Clearance (CL/F) for Cycle 1 Day 15 in the 500 mg BID Group [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.
Measure Participants	13
Geometric Mean (Geometric Coefficient of Variation) [Liters per hour (L/hr)]	85.09 (36)

18. Secondary Outcome

Title	PF-04136309 Plasma Decay Half-Life (t1/2) for Cycle 1 Day 15 [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	1	10
Mean (Standard Deviation) [hours (hr)]	1.18 (NA)	3.41 (0.996)

19. Secondary Outcome

Title	PF-04136309 Apparent Volume of Distribution (Vz/F) for Cycle 1 Day 15 [Phase 1b]
Description	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.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	1	10
Geometric Mean (Geometric Coefficient of Variation) [Liters (L)]	120 (NA)	398.3 (NA)

20. Secondary Outcome

Title	Ex Vivo Inhibition of Chemokine Ligand 2 (CCL2)-Induced Extracellular Signal Regulated Kinase (ERK) Phosphorylation in the Peripheral Blood [Phase 1b]
Description	A drop in the CCL2-induced ERK kinase phosphorylation (pERK) biomarker level indicates target engagement (TE).
Time Frame	Cycle 1 Day 1 pre-dose, 2 and 6 hours post-dose, and 12 hours (pre-second BID dose-optional collection); Cycle 1 Days 2, 3 and 4 pre-dose

Outcome Measure Data

Analysis Population Description

No data to report for this outcome measure as only individual plots were planned and generated to show the trend of biomarker level in each participant. Summary statistics were not planned and hence not generated.

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	0	0

21. Other Pre-specified Outcome

Title	Objective Response Rate (ORR) [Phase 1b]
Description	ORR was defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1, relative to all randomized participants who had baseline measurable disease. Confirmed responses were those that persisted on repeat imaging study ≥4 weeks after initial documentation of response.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine	Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.	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.
Measure Participants	4	17
Number (95% Confidence Interval) [Percentage of Participants]	0 0%	29.4 172.9%

22. Secondary Outcome

Title	Number of Participants With Overall Survival (OS) [Phase 2]
Description	OS was defined as the time from date of randomization to date of death due to any cause. For participants not expiring, their survival times were to be censored at the last date they were known to be alive. Participants lacking data beyond the day of randomization were to have their survival times censored at the date of randomization with duration of 1 day.
Time Frame	Up to approximately 13.5 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

23. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) [Phase 2]
Description	An AE was any untoward medical occurrence in a participant administered a product or medical device 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.
Time Frame	Up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

24. Secondary Outcome

Title	Number of Participants With Laboratory Abnormalities by Severity [Phase 2]
Description	Hematology, chemistry, and urinalysis laboratory parameters were to be analyzed and graded by NCI CTCAE version 4.03.
Time Frame	Up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

25. Secondary Outcome

Title	Objective Response Rate (ORR) [Phase 2]
Description	ORR was defined as the percentage of participants with confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1, relative to all randomized participants who had baseline measurable disease. Confirmed responses were those that persisted on repeat imaging study ≥4 weeks after initial documentation of response.
Time Frame	Up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

26. Secondary Outcome

Title	Duration of Objective Response (DR) [Phase 2]
Description	DR was defined as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. DR data were to be censored on the day following the date of the last on treatment (including 28 day follow-up period after last dose) tumor assessment documenting absence of progressive disease for participants who did not have objective tumor progression and who did not die due to any cause while on treatment or who were given anti-tumor treatment other than the study treatment prior to observing objective tumor progression. Participants who achieved a PR and then a CR were to have times calculated using the date of the PR as the first day. DR was only to be calculated for the subgroup of participants with objective response.
Time Frame	Up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

27. Secondary Outcome

Title	Time to Progression (TTP) With the Double Combination PF-04136309 and Gemcitabine (Maintenance Therapy) After Interruption of Nab-paclitaxel [Phase 2]
Description	This type of TTP was defined as the time from interruption of nab-paclitaxel to the first documentation of objective tumor progression. This TTP was to be only calculated for the subgroup of participants who were treated with the maintenance therapy.
Time Frame	Up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

28. Secondary Outcome

Title	Trough PF-04136309 Concentrations [Phase 2]
Description	The minimum plasma concentration of PF-04136309.
Time Frame	Cycle 1 Day 1 pre-dose, Cycle 1 Days 2, 8 and 15 pre-dose; Day 1 of Cycle 2 and subsequent cycles pre-dose, and EOT visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

29. Secondary Outcome

Title	Change From Baseline in Pharmacodynamic (PD) Markers in Metastatic Tumors and Bone Marrow [Phase 2]
Description	Collections of core needle biopsy (CNB) from a metastatic site or fine-needle aspirate (FNA) from the primary tumor tissue were optional but at least 12 paired biopsies would have to be available and fully assessable in each treatment arm to allow the comparison.
Time Frame	Baseline, Cycle 1 Day 28 or Cycle 2 Day 28; EOT visit (optional) for CNB

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

30. Secondary Outcome

Title	Number of Participants With Peripheral Neurological Adverse Events [Phase 2]
Description	To evaluate the improvement of peripheral neurotoxicity induced by nab-paclitaxel by the addition of PF-04136309 to the combination therapy of nab-paclitaxel plus gemcitabine.
Time Frame	Up to approximately 1 year

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase 2: PF-04136309 or Placebo + Nab-paclitaxel + Gemcitabine
Arm/Group Description	In Phase 2 part of the study which was not conducted due to early termination, participants were to be randomized with a 1:1 to receive either PF-04136309 or placebo in combination with nab-paclitaxel + gemcitabine. The dose of PF-04136309 was to be the recommended Phase 2 dose (RP2D) determined in the Phase 1b part of the study.
Measure Participants	0

Adverse Events

Time Frame	AE data were collected from baseline through 28 days after last dose of study treatment (up to approximately 1 year).
Adverse Event Reporting Description	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).
Arm/Group Title	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine		Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
Arm/Group Description	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.		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.
All Cause Mortality
	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine		Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		11/17 (64.7%)
Serious Adverse Events
	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine		Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		11/17 (64.7%)
Eye disorders
Episcleritis	0/4 (0%)		1/17 (5.9%)
Gastrointestinal disorders
Abdominal pain	0/4 (0%)		2/17 (11.8%)
Gastrooesophageal reflux disease	1/4 (25%)		0/17 (0%)
Small intestinal obstruction	0/4 (0%)		1/17 (5.9%)
General disorders
Chest pain	0/4 (0%)		1/17 (5.9%)
Pyrexia	0/4 (0%)		2/17 (11.8%)
Infections and infestations
Biliary sepsis	0/4 (0%)		1/17 (5.9%)
Cellulitis	1/4 (25%)		0/17 (0%)
Klebsiella bacteraemia	0/4 (0%)		1/17 (5.9%)
Liver abscess	0/4 (0%)		1/17 (5.9%)
Pneumonia	0/4 (0%)		1/17 (5.9%)
Sepsis	0/4 (0%)		1/17 (5.9%)
Metabolism and nutrition disorders
Decreased appetite	1/4 (25%)		0/17 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	0/4 (0%)		1/17 (5.9%)
Neck pain	0/4 (0%)		1/17 (5.9%)
Nervous system disorders
Cognitive disorder	1/4 (25%)		0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/4 (0%)		1/17 (5.9%)
Hypoxia	0/4 (0%)		1/17 (5.9%)
Pneumonitis	0/4 (0%)		3/17 (17.6%)
Skin and subcutaneous tissue disorders
Rash	1/4 (25%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Phase 1b: PF-04136309 750 mg BID +Nab-paclitaxel +Gemcitabine		Phase 1b: PF-04136309 500 mg BID +Nab-paclitaxel +Gemcitabine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100%)		17/17 (100%)
Blood and lymphatic system disorders
Anaemia	2/4 (50%)		11/17 (64.7%)
Leukocytosis	0/4 (0%)		2/17 (11.8%)
Leukopenia	3/4 (75%)		4/17 (23.5%)
Lymphopenia	1/4 (25%)		5/17 (29.4%)
Neutropenia	3/4 (75%)		4/17 (23.5%)
Thrombocytopenia	2/4 (50%)		3/17 (17.6%)
Cardiac disorders
Sinus tachycardia	0/4 (0%)		1/17 (5.9%)
Tachycardia	1/4 (25%)		2/17 (11.8%)
Ear and labyrinth disorders
Ear discomfort	0/4 (0%)		1/17 (5.9%)
Eye disorders
Cataract	1/4 (25%)		0/17 (0%)
Erythema of eyelid	0/4 (0%)		1/17 (5.9%)
Eye pain	0/4 (0%)		1/17 (5.9%)
Eyelid oedema	0/4 (0%)		1/17 (5.9%)
Lacrimation increased	0/4 (0%)		1/17 (5.9%)
Photophobia	0/4 (0%)		1/17 (5.9%)
Vision blurred	0/4 (0%)		3/17 (17.6%)
Gastrointestinal disorders
Abdominal discomfort	0/4 (0%)		3/17 (17.6%)
Abdominal distension	0/4 (0%)		2/17 (11.8%)
Abdominal pain	1/4 (25%)		5/17 (29.4%)
Abdominal pain upper	1/4 (25%)		2/17 (11.8%)
Abdominal tenderness	0/4 (0%)		1/17 (5.9%)
Aphthous ulcer	0/4 (0%)		1/17 (5.9%)
Ascites	0/4 (0%)		3/17 (17.6%)
Constipation	3/4 (75%)		7/17 (41.2%)
Diarrhoea	1/4 (25%)		7/17 (41.2%)
Dry mouth	0/4 (0%)		2/17 (11.8%)
Dyspepsia	0/4 (0%)		1/17 (5.9%)
Dysphagia	0/4 (0%)		1/17 (5.9%)
Epigastric discomfort	0/4 (0%)		1/17 (5.9%)
Faeces soft	0/4 (0%)		1/17 (5.9%)
Flatulence	0/4 (0%)		2/17 (11.8%)
Gastrointestinal sounds abnormal	0/4 (0%)		1/17 (5.9%)
Gastrooesophageal reflux disease	0/4 (0%)		1/17 (5.9%)
Gingival pain	0/4 (0%)		1/17 (5.9%)
Haemorrhoids	1/4 (25%)		0/17 (0%)
Inguinal hernia	0/4 (0%)		1/17 (5.9%)
Nausea	4/4 (100%)		14/17 (82.4%)
Oral mucosal eruption	1/4 (25%)		0/17 (0%)
Oral pain	0/4 (0%)		1/17 (5.9%)
Pancreatic failure	0/4 (0%)		1/17 (5.9%)
Parotid gland enlargement	0/4 (0%)		1/17 (5.9%)
Stomatitis	1/4 (25%)		0/17 (0%)
Vomiting	3/4 (75%)		7/17 (41.2%)
General disorders
Asthenia	0/4 (0%)		3/17 (17.6%)
Chest discomfort	0/4 (0%)		3/17 (17.6%)
Chills	2/4 (50%)		4/17 (23.5%)
Device related thrombosis	0/4 (0%)		1/17 (5.9%)
Discomfort	0/4 (0%)		1/17 (5.9%)
Early satiety	0/4 (0%)		1/17 (5.9%)
Fatigue	4/4 (100%)		13/17 (76.5%)
Malaise	2/4 (50%)		2/17 (11.8%)
Mucosal inflammation	1/4 (25%)		0/17 (0%)
Oedema peripheral	1/4 (25%)		8/17 (47.1%)
Pain	1/4 (25%)		3/17 (17.6%)
Pyrexia	2/4 (50%)		10/17 (58.8%)
Suprapubic pain	1/4 (25%)		0/17 (0%)
Xerosis	0/4 (0%)		1/17 (5.9%)
Hepatobiliary disorders
Jaundice	0/4 (0%)		1/17 (5.9%)
Portal vein thrombosis	0/4 (0%)		1/17 (5.9%)
Infections and infestations
Cellulitis	2/4 (50%)		1/17 (5.9%)
Device related infection	1/4 (25%)		1/17 (5.9%)
Localised infection	0/4 (0%)		1/17 (5.9%)
Nasopharyngitis	0/4 (0%)		1/17 (5.9%)
Oral candidiasis	0/4 (0%)		1/17 (5.9%)
Pharyngitis	0/4 (0%)		1/17 (5.9%)
Rhinitis	0/4 (0%)		2/17 (11.8%)
Sinusitis	0/4 (0%)		2/17 (11.8%)
Skin infection	0/4 (0%)		1/17 (5.9%)
Tooth infection	0/4 (0%)		1/17 (5.9%)
Upper respiratory tract infection	0/4 (0%)		1/17 (5.9%)
Urinary tract infection	0/4 (0%)		2/17 (11.8%)
Injury, poisoning and procedural complications
Fall	0/4 (0%)		1/17 (5.9%)
Procedural pain	0/4 (0%)		1/17 (5.9%)
Investigations
Activated partial thromboplastin time prolonged	0/4 (0%)		2/17 (11.8%)
Alanine aminotransferase	0/4 (0%)		2/17 (11.8%)
Alanine aminotransferase increased	3/4 (75%)		7/17 (41.2%)
Aspartate aminotransferase	0/4 (0%)		1/17 (5.9%)
Aspartate aminotransferase increased	1/4 (25%)		6/17 (35.3%)
Blood albumin	0/4 (0%)		1/17 (5.9%)
Blood albumin decreased	0/4 (0%)		1/17 (5.9%)
Blood alkaline phosphatase	0/4 (0%)		1/17 (5.9%)
Blood alkaline phosphatase increased	0/4 (0%)		7/17 (41.2%)
Blood bilirubin increased	0/4 (0%)		4/17 (23.5%)
Blood creatinine increased	0/4 (0%)		1/17 (5.9%)
C-reactive protein increased	0/4 (0%)		1/17 (5.9%)
Immunoglobulins decreased	0/4 (0%)		1/17 (5.9%)
International normalised ratio increased	0/4 (0%)		2/17 (11.8%)
Lymphocyte count decreased	0/4 (0%)		4/17 (23.5%)
Monocyte count increased	0/4 (0%)		1/17 (5.9%)
Neutrophil count	0/4 (0%)		1/17 (5.9%)
Neutrophil count decreased	0/4 (0%)		4/17 (23.5%)
Platelet count decreased	0/4 (0%)		3/17 (17.6%)
Weight decreased	1/4 (25%)		9/17 (52.9%)
Weight increased	0/4 (0%)		1/17 (5.9%)
White blood cell count decreased	0/4 (0%)		4/17 (23.5%)
White blood cells urine positive	0/4 (0%)		1/17 (5.9%)
Metabolism and nutrition disorders
Decreased appetite	2/4 (50%)		6/17 (35.3%)
Dehydration	1/4 (25%)		2/17 (11.8%)
Diabetes mellitus	0/4 (0%)		1/17 (5.9%)
Hyperglycaemia	1/4 (25%)		8/17 (47.1%)
Hyperkalaemia	0/4 (0%)		1/17 (5.9%)
Hypermagnesaemia	0/4 (0%)		1/17 (5.9%)
Hypertriglyceridaemia	0/4 (0%)		1/17 (5.9%)
Hypoalbuminaemia	0/4 (0%)		4/17 (23.5%)
Hypocalcaemia	0/4 (0%)		1/17 (5.9%)
Hypokalaemia	0/4 (0%)		4/17 (23.5%)
Hypomagnesaemia	0/4 (0%)		3/17 (17.6%)
Hyponatraemia	0/4 (0%)		3/17 (17.6%)
Hypophosphataemia	0/4 (0%)		2/17 (11.8%)
Type 2 diabetes mellitus	0/4 (0%)		1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/4 (0%)		1/17 (5.9%)
Back pain	0/4 (0%)		3/17 (17.6%)
Bone pain	1/4 (25%)		0/17 (0%)
Exostosis	0/4 (0%)		1/17 (5.9%)
Flank pain	0/4 (0%)		1/17 (5.9%)
Limb discomfort	0/4 (0%)		1/17 (5.9%)
Musculoskeletal chest pain	0/4 (0%)		1/17 (5.9%)
Myalgia	0/4 (0%)		4/17 (23.5%)
Neck pain	1/4 (25%)		1/17 (5.9%)
Pain in extremity	2/4 (50%)		4/17 (23.5%)
Nervous system disorders
Dizziness	0/4 (0%)		4/17 (23.5%)
Dysaesthesia	0/4 (0%)		1/17 (5.9%)
Dysgeusia	1/4 (25%)		2/17 (11.8%)
Fine motor skill dysfunction	0/4 (0%)		1/17 (5.9%)
Headache	0/4 (0%)		5/17 (29.4%)
Mental impairment	0/4 (0%)		1/17 (5.9%)
Neuropathy peripheral	1/4 (25%)		9/17 (52.9%)
Paraesthesia	0/4 (0%)		1/17 (5.9%)
Peripheral sensory neuropathy	1/4 (25%)		0/17 (0%)
Presyncope	0/4 (0%)		1/17 (5.9%)
Syncope	0/4 (0%)		1/17 (5.9%)
Psychiatric disorders
Affective disorder	0/4 (0%)		1/17 (5.9%)
Anxiety	1/4 (25%)		3/17 (17.6%)
Depression	0/4 (0%)		3/17 (17.6%)
Insomnia	2/4 (50%)		8/17 (47.1%)
Renal and urinary disorders
Chromaturia	0/4 (0%)		2/17 (11.8%)
Proteinuria	0/4 (0%)		1/17 (5.9%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/4 (0%)		1/17 (5.9%)
Erectile dysfunction	0/4 (0%)		1/17 (5.9%)
Vaginal haemorrhage	1/4 (25%)		0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/4 (25%)		4/17 (23.5%)
Dysphonia	0/4 (0%)		3/17 (17.6%)
Dyspnoea	1/4 (25%)		3/17 (17.6%)
Dyspnoea exertional	0/4 (0%)		4/17 (23.5%)
Epistaxis	0/4 (0%)		4/17 (23.5%)
Hiccups	0/4 (0%)		2/17 (11.8%)
Hypoxia	0/4 (0%)		1/17 (5.9%)
Nasal congestion	0/4 (0%)		1/17 (5.9%)
Oropharyngeal pain	0/4 (0%)		2/17 (11.8%)
Pleural effusion	0/4 (0%)		1/17 (5.9%)
Pulmonary embolism	0/4 (0%)		2/17 (11.8%)
Rhinorrhoea	0/4 (0%)		1/17 (5.9%)
Upper-airway cough syndrome	0/4 (0%)		1/17 (5.9%)
Skin and subcutaneous tissue disorders
Alopecia	3/4 (75%)		10/17 (58.8%)
Dermatitis acneiform	0/4 (0%)		2/17 (11.8%)
Erythema	1/4 (25%)		1/17 (5.9%)
Hyperhidrosis	1/4 (25%)		0/17 (0%)
Lichenoid keratosis	0/4 (0%)		1/17 (5.9%)
Nail bed disorder	0/4 (0%)		1/17 (5.9%)
Nail discolouration	0/4 (0%)		1/17 (5.9%)
Night sweats	0/4 (0%)		3/17 (17.6%)
Onycholysis	0/4 (0%)		1/17 (5.9%)
Pruritus	0/4 (0%)		1/17 (5.9%)
Rash	3/4 (75%)		8/17 (47.1%)
Rash maculo-papular	1/4 (25%)		4/17 (23.5%)
Skin hyperpigmentation	0/4 (0%)		1/17 (5.9%)
Vascular disorders
Hot flush	1/4 (25%)		0/17 (0%)
Hypertension	1/4 (25%)		4/17 (23.5%)
Hypotension	0/4 (0%)		2/17 (11.8%)
Infarction	1/4 (25%)		0/17 (0%)
Peripheral embolism	0/4 (0%)		1/17 (5.9%)
Phlebitis	0/4 (0%)		1/17 (5.9%)
Thrombophlebitis superficial	1/4 (25%)		1/17 (5.9%)

Limitations/Caveats

The study was terminated prematurely based on the company's change in prioritization for the portfolio and was not due to any safety concerns or regulatory interactions.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.