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Dose-Escalation Study Of Palbociclib + Nab-Paclitaxel In mPDAC

Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02501902
Collaborator
Celgene (Industry)
76
Enrollment
26
Locations
1
Arm
37.1
Actual Duration (Months)
2.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 1, open label, multi center, multiple dose, dose escalation, safety, pharmacokinetic and pharmacodynamic study of palbociclib in combination with nab-P, in sequential cohorts of adult patients with mPDAC, with MTD expansion cohort(s). Approximately 30-60 patients are expected to be enrolled in the overall study.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

The study has 2 parts:

• Part A (Dose-Escalation Cohorts): Consecutive cohorts of patients will receive escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles, in order to estimate the MTD(s) of the combination. The starting doses will be 75 mg palbociclib, and 100 mg/m2 nab-P. The observation period for dose-limiting toxicities (DLTs) will be from Day 1 to Day 28. Pharmacokinetic (PK) and pharmacodynamic (PD) properties of palbociclib and nab-P will also be assessed. Up to approximately 30 patients will be enrolled. The criteria for dose escalation will be based on a modified toxicity probability interval (mTPI) method.

• Part B [MTD Expansion Cohort(s)]: When the MTD(s) of palbociclib plus nab-P has been estimated with confidence, enrollment will proceed into 1 or 2 MTD expansion cohort(s) of up to 20 patients each at the MTD(s). The objective of the MTD expansion cohort(s) will be to provide additional information on safety, tolerability, biomarkers, PD activity, and PK/PD relationship for the combination regimen in order to determine the RP2D. The MTD expansion cohort(s) will only enroll patients who have not received previous treatment for their metastatic disease in order to evaluate preliminary activity of the combination in the target patient population.

All patients (in Part A and B) will receive nab-P intravenously once weekly for 3 weeks out of each 28-day cycle. Palbociclib oral dosing will be once daily on Days 1-21 of each 28-day cycle. To allow for PK evaluation of nab-P administered alone, nab-P will be administered on Day -2 for Cycle 1 only. Subsequent cycles will administer both nab-P and palbociclib on Day

  1. Alternate dosing schedules for palbociclib may be explored based on emerging PK, PD, and safety data.

Patients will be treated as long as they are clinically benefiting from investigational product without unacceptable toxicity, objective disease progression, or withdrawal of consent. A modified visit schedule will be implemented for patients who are on investigational product for more than 2 years.

Study Design

Study Type:
Interventional
Actual Enrollment :
76 participants
Allocation:
N/A
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
AN OPEN-LABEL PHASE IB STUDY OF PALBOCICLIB (ORAL CDK 4/6 INHIBITOR) PLUS ABRAXANE (REGISTERED) (NAB-PACLITAXEL) IN PATIENTS WITH METASTATIC PANCREATIC DUCTAL ADENOCARCINOMA
Actual Study Start Date :
Nov 23, 2015
Actual Primary Completion Date :
Oct 10, 2018
Actual Study Completion Date :
Dec 27, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Palbociclib + Nab-Paclitaxel

Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle. Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.

Drug: Palbociclib
Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle.
Other Names:
  • Ibrance

    • Drug: Nab-Paclitaxel
    Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.
    Other Names:
  • Abraxane

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Dose Limiting Toxicities [From Day 1 until pre-dose Cycle 2 Day 1]

      Adverse events (AEs) considered as dose limiting toxicities (DLTs) included: hematologic: Grade 4 neutropenia lasting >4 days; Febrile neutropenia (defined as neutropenia Grade>=3 [absolute neutrophil count {ANC}<1000 cells/cubic millimeter {mm^3}] and a body temperature >=38.5 [degrees centigrade]℃) requiring antibiotic or antifungal treatment; any Grade 4 thrombocytopenia (<25000/mm^3 or 25.0*10^9/[liter]L). Non-hematologic: Grade >=3 toxicities, except those that had not been maximally treated (eg, nausea, vomiting, diarrhea). Any AE that caused a palbociclib treatment interruption of greater than 7 consecutive days or caused any combination of interruption/reduction for >=14 days. Any AE that caused omission or reduction of at least 2 of the 3 weekly doses of nab-P.

    Secondary Outcome Measures

    1. Number of Participants With Adverse Events [From the signing of informed consent up to 56 days after the last administration of the investigational product, or 365 days from the first dose of investigational product, whichever is later]

      An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An serious AE (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; 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 investigational product. Disease progression was not considered a treatment emergent AE unless the participant died of disease prior to 28 days after discontinuation of treatment. Treatment emergent AEs with cause possibly, probably or definitely related to treatment, as judged by the investigator, were defined as treatment-related AEs. AEs were graded by investigator according to CTCAE v4.03.

    2. Number of Participants With Laboratory Abnormalities [From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).]

      The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to NCI CTCAE v4.0 were summarized: hematology (anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils, platelets and white blood cells) and chemistry laboratory tests (alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin, creatinine, hypercalcemia, hyperglocemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase).

    3. Number of Participants With Vital Signs Data Meeting Pre-specified Criteria [From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).]

      Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Suggest text: Vital signs categorical summary included: 1)SBP>150mmHg or DBP>100mmHg; 2)SBP>200mmHg or DBP>110mmHg; 3)SBP increase >=20 and <40mmHg; 4)SBP increase >=40 and <60mmHg; 5)SBP increase>=60mmHg; 6)DBP increase >=10 and <20mmHg; 7)DBP increase >=20 and <30mmHg; 8)DBP increase >=30mmHg; 9)pulse rate>120bpm; 10)pulse rate<50bpm.

    4. Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 [From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).]

      Carbohydrate antigen 19-9 (Ca19-9) is a clinical pharmacodynamic (PD) marker associated with metastatic pancreatic ductal adenocarcinoma (mPDAC).

    5. Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 [From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).]

      Ca19-9 is a clinical PD marker associated with metastatic mPDAC.

    6. Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 [From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).]

      Ca19-9 is a clinical PD marker associated with metastatic mPDAC.

    7. Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 [From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).]

      Ca19-9 is a clinical PD marker associated with metastatic mPDAC.

    8. Objective Response Rate [From screening to 365 days from the last dose of investigational product]

      Percentage of participants who achieved objective response (OR) based on investigator assessment is presented. OR is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Objective response rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR relative to all anti-tumor evaluable participants.

    9. Duration of Response [From screening to 365 days from the last dose of investigational product]

      The duration of response was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. Disease progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm.

    10. Progression Free Survival [From screening to 365 days from the last dose of investigational product]

      The progression free survival (PFS) was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression as per RECIST v1.1 or death due to any cause in the absence of documented progression disease, whichever occurred first.

    11. Six-month Progression-free Survival Rate (6m-PFSR) [From screening to 6 months after first dose of investigational product]

      6m-PFS was defined as PFS status (progression free and alive, or not) at Month 6. It was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.

    12. Overall Survival (OS) [From screening to 365 days from the last dose of investigational product]

      OS was defined as the time from the date of first dose to the date of death due to any cause. Following the end of treatment visit, survival status was collected in all participants every month until 12 months (365 days) had elapsed from the last dose of investigational product.

    13. Number of Participants With Positive p16 [From Day-2 to up to 63 days from last dose of investigational product]

      p16 is a tumor suppressor protein which plays an important role in cell cycle regulation. The analysis of biomarker p16 expression might aid in the identification of patient subpopulations most likely to benefit from treatment. The results from p16 expression testing by immunohistochemistry (IHC) was used for sensitivity analyses. (a) and (b) :p16 cutoff utilizing the optimal cut point identified by the ORC analysis for the OS (a) or PFS (b) and the p16 positive tumor cells.

    14. Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) [From Day-2 to up to 63 days from last dose of investigational product]

      Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses.

    15. Rb H-score Nuclear Staining [From Day-2 to up to 63 days from last dose of investigational product]

      Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors. The score is obtained by the formula: 3*percentage of strongly staining nuclei + 2*percentage of moderately staining nuclei + percentage of weakly staining nuclei, giving the range of 0 to 300

    16. Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) [Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.]

      The palbociclib multiple dose maximum plasma concentration(Cmax) was observed directly from data.

    17. Palbociclib Multiple Dose Time for Cmax (Tmax) [Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.]

      The palbociclib multiple dose time for Cmax (Tmax) was observed directly from data.

    18. Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) [Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.]

      The palbociclib area under the plasma concentration-time curve for dosing interval τ (AUCτ) was observed directly from data.

    19. Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) [Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.]

      The palbociclib multiple dose trough plasma concentration (Ctrough) was observed directly from data.

    20. Palbociclib Multiple Dose Apparent Clearance (CL/F) [Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.]

      The palbociclib multiple dose apparent clearance (CL/F) was observed directly from data.

    21. Nab-P Cmax [Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.]

      The nab-P Cmax on Cycle 1 Day -1 and Day 13 were observed directly from data.

    22. Nab-P Tmax [Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.]

      The nab-P Tmax on Day -1 and Day 13 were observed directly from data.

    23. Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) [Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.]

      The nab-P area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) on Day -1 and Day 13 were observed directly from data.

    24. Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) [Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.]

      The nab-P area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUCinf) on Day -1 and Day 13 observed directly from data.

    25. Nab-P Terminal Plasma Elimination Half-life (t1/2) [Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.]

      The nab-P t1/2 on Day -1 and Day 13 were observed directly from data.

    26. Nab-P Clearance (CL) [Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.]

      The nab-P clearance on Day -1 and Day 13 were observed directly from data.

    27. Nab-P Volume of Distribution (Vz) [Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.]

      The nab-P on Day -1 and Day 13 were observed directly from data.

    Eligibility Criteria

    Criteria

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

    • Histologically or cytologically-confirmed metastatic pancreatic ductal adenocarcinoma.

    • Availability of a tumor tissue specimen. If no archived tumor tissue is available, then a de novo biopsy is required for patient participation.

    • Karnofsky Performance Status 70 or greater.

    • Adequate Bone Marrow, Renal, and Liver Function.

    Exclusion Criteria:

    • Prior treatment with a CDK 4/6 inhibitor.

    • Prior treatment with nab-P for the treatment of metastatic disease.

    • Patients with known CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth.

    • Diagnosis of any other malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix.

    • QTc >480 msec, or family or personal history of long or short QT syndrome, Brugada syndrome or known history of QTc prolongation, or Torsade de Pointes.

    • Uncontrolled electrolyte disorders.

    • Cardiac or pulmonary disorders within 6 months of enrollment.

    • Known human immunodeficiency virus infection.

    • History of interstitial lung disease or pneumonitis.

    • Other severe acute or chronic medical or psychiatric condition that may increase the risk associated with study participation.

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-P.

    • Difficulty swallowing capsules or requirement for a feeding tube.

    • Previous high-dose chemotherapy requiring stem cell rescue.

    • Pregnant female patients; breastfeeding female patients; male patients with partners currently pregnant.

    • Active inflammatory or other gastrointestinal disease,

    • Active bleeding disorder in the past 6 months.

    • Patients treated within the last 7 days prior to the start of IP with strong/moderate CYP3A4 inhibitors, strong/moderate CYP3A4 inducers, CYP2C8 inhibitors, strong/moderate CYP2C8 inducers, or drugs that are known to prolong the QT interval.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Scottsdale Healthcare Hospitals DBA HonorHealth Scottsdale Arizona United States 85258
    2 Virginia G. Piper Cancer Pharmacy Scottsdale Arizona United States 85258
    3 UC San Diego Medical Center - La Jolla (Thornton Hospital) La Jolla California United States 92037-0845
    4 UC San Diego Moores Cancer Center - Investigational Drug Services La Jolla California United States 92037-0845
    5 UC San Diego Moores Cancer Center La Jolla California United States 92093
    6 UC San Diego Medical Center - Hillcrest San Diego California United States 92103
    7 Anschutz Cancer Pavilion Aurora Colorado United States 80045
    8 University of Colorado Cancer Center Aurora Colorado United States 80045
    9 University of Colorado Denver, CTO (CTRC) Aurora Colorado United States 80045
    10 University of Colorado Hospital - Anschutz Inpatient Pavilion (AIP) Aurora Colorado United States 80045
    11 University of Colorado Hospital - Anschutz Outpatient Pavilion (AOP) Aurora Colorado United States 80045
    12 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore Maryland United States 21231-1000
    13 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    14 Siteman Cancer Center - West County Creve Coeur Missouri United States 63141
    15 Barnes-Jewish Hospital Saint Louis Missouri United States 63110
    16 Washington University Infusion Center Pharmacy Saint Louis Missouri United States 63110
    17 Washington University School of Medicine Saint Louis Missouri United States 63110
    18 Siteman Cancer Center - South County Saint Louis Missouri United States 63129
    19 Siteman Cancer Center Saint Peters Missouri United States 63376
    20 University of Utah, Huntsman Cancer Hospital Salt Lake City Utah United States 84112
    21 University of Utah, Huntsman Cancer Institute Salt Lake City Utah United States 84112
    22 Hospital Universitario de Fuenlabrada. Unidad de Farmacia Fuenlabrada Madrid Spain 28942
    23 Hospital Universitario Fuenlabrada Fuenlabrada Madrid Spain 28942
    24 Hospital Universitari Vall D'Hebron, Servicio de Oncología Médica Barcelona Spain 08035
    25 Hospital Universitario 12 de Octubre Servicio de Farmacia Madrid Spain 28041
    26 Hospital Universitario 12 de Octubre Madrid Spain 28041

    Sponsors and Collaborators

    • Pfizer
    • Celgene

    Investigators

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

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT02501902
    Other Study ID Numbers:
    • A5481059
    • 2015-001307-31
    First Posted:
    Jul 17, 2015
    Last Update Posted:
    Apr 6, 2021
    Last Verified:
    Mar 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Pfizer
    Ibrance, palbociclib, Abraxane, nab-paclitaxel, pancreas,
    Additional relevant MeSH terms:
    Adenocarcinoma
    Paclitaxel
    Palbociclib

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This was a multiple dose, dose escalation study of palbociclib in combination with nab-paclitaxel (nab-P), in sequential cohorts of adult participants.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100mg/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100 mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts.
    Period Title: Overall Study
    STARTED 3 7 4 11 11 11 9 20
    COMPLETED 0 0 0 0 0 0 0 0
    NOT COMPLETED 3 7 4 11 11 11 9 20

    Baseline Characteristics

    Arm/Group Title DL1 Palbociclib 75 mg/Nab-Paclitaxel 100 mg /m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100mg/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100 mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Total
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-paclitaxel 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. Total of all reporting groups
    Overall Participants 3 7 4 11 11 11 9 20 76
    Age, Customized (Count of Participants)
    <18
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    18-44
    0
    0%
    1
    14.3%
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    2
    10%
    4
    5.3%
    45-64
    2
    66.7%
    5
    71.4%
    3
    75%
    5
    45.5%
    6
    54.5%
    7
    63.6%
    8
    88.9%
    9
    45%
    45
    59.2%
    65-75
    1
    33.3%
    1
    14.3%
    1
    25%
    5
    45.5%
    5
    45.5%
    4
    36.4%
    1
    11.1%
    9
    45%
    27
    35.5%
    >75
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    2
    66.7%
    5
    71.4%
    1
    25%
    6
    54.5%
    5
    45.5%
    3
    27.3%
    6
    66.7%
    6
    30%
    34
    44.7%
    Male
    1
    33.3%
    2
    28.6%
    3
    75%
    5
    45.5%
    6
    54.5%
    8
    72.7%
    3
    33.3%
    14
    70%
    42
    55.3%
    Race/Ethnicity, Customized (Count of Participants)
    White
    3
    100%
    6
    85.7%
    4
    100%
    11
    100%
    11
    100%
    11
    100%
    8
    88.9%
    20
    100%
    74
    97.4%
    Asian
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    2
    2.6%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Dose Limiting Toxicities
    Description Adverse events (AEs) considered as dose limiting toxicities (DLTs) included: hematologic: Grade 4 neutropenia lasting >4 days; Febrile neutropenia (defined as neutropenia Grade>=3 [absolute neutrophil count {ANC}<1000 cells/cubic millimeter {mm^3}] and a body temperature >=38.5 [degrees centigrade]℃) requiring antibiotic or antifungal treatment; any Grade 4 thrombocytopenia (<25000/mm^3 or 25.0*10^9/[liter]L). Non-hematologic: Grade >=3 toxicities, except those that had not been maximally treated (eg, nausea, vomiting, diarrhea). Any AE that caused a palbociclib treatment interruption of greater than 7 consecutive days or caused any combination of interruption/reduction for >=14 days. Any AE that caused omission or reduction of at least 2 of the 3 weekly doses of nab-P.
    Time Frame From Day 1 until pre-dose Cycle 2 Day 1

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product and met the measurable criteria.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle.
    Measure Participants 3 7 4 11 11 11 6
    Count of Participants [Participants]
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    1
    9.1%
    1
    9.1%
    1
    11.1%
    2. Secondary Outcome
    Title Number of Participants With Adverse Events
    Description An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An serious AE (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; 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 investigational product. Disease progression was not considered a treatment emergent AE unless the participant died of disease prior to 28 days after discontinuation of treatment. Treatment emergent AEs with cause possibly, probably or definitely related to treatment, as judged by the investigator, were defined as treatment-related AEs. AEs were graded by investigator according to CTCAE v4.03.
    Time Frame From the signing of informed consent up to 56 days after the last administration of the investigational product, or 365 days from the first dose of investigational product, whichever is later

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 4 11 11 11 9 20 27
    All causality treatment-emergent AEs
    3
    100%
    7
    100%
    4
    100%
    11
    100%
    11
    100%
    11
    100%
    9
    100%
    20
    100%
    27
    35.5%
    Treatment-related treatment-emergent AEs
    3
    100%
    7
    100%
    4
    100%
    10
    90.9%
    11
    100%
    11
    100%
    9
    100%
    20
    100%
    27
    35.5%
    All causality SAEs
    2
    66.7%
    4
    57.1%
    3
    75%
    4
    36.4%
    6
    54.5%
    9
    81.8%
    2
    22.2%
    12
    60%
    15
    19.7%
    Treatment-related SAES
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    2
    18.2%
    4
    36.4%
    1
    11.1%
    6
    30%
    6
    7.9%
    All causality Grade 3 or 4 AEs
    3
    100%
    6
    85.7%
    3
    75%
    9
    81.8%
    11
    100%
    10
    90.9%
    5
    55.6%
    20
    100%
    27
    35.5%
    Treatment-related Grade 3 or 4 AEs
    2
    66.7%
    5
    71.4%
    2
    50%
    8
    72.7%
    11
    100%
    7
    63.6%
    4
    44.4%
    20
    100%
    27
    35.5%
    All causality Grade 5 AEs
    0
    0%
    1
    14.3%
    1
    25%
    1
    9.1%
    3
    27.3%
    5
    45.5%
    0
    0%
    1
    5%
    2
    2.6%
    Treatment-related Grade 5 AEs
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title Number of Participants With Laboratory Abnormalities
    Description The number of participants with following laboratory abnormalities meeting any of the Grades 1 to 4 classified according to NCI CTCAE v4.0 were summarized: hematology (anemia, hemoglobin increased, lymphocyte count increased, lymphopenia, neutrophils, platelets and white blood cells) and chemistry laboratory tests (alanine aminotransferase, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin, creatinine, hypercalcemia, hyperglocemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, lipase).
    Time Frame From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 4 11 11 11 9 20 27
    Anemia
    3
    100%
    7
    100%
    4
    100%
    11
    100%
    11
    100%
    11
    100%
    8
    88.9%
    20
    100%
    27
    35.5%
    Hemoglobin increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5%
    1
    1.3%
    Lymphocyte count increased
    0
    0%
    1
    14.3%
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lymphopenia
    3
    100%
    7
    100%
    2
    50%
    9
    81.8%
    10
    90.9%
    11
    100%
    7
    77.8%
    20
    100%
    27
    35.5%
    Neutrophils (absolute)
    3
    100%
    7
    100%
    2
    50%
    10
    90.9%
    10
    90.9%
    9
    81.8%
    8
    88.9%
    20
    100%
    27
    35.5%
    Platelets
    2
    66.7%
    4
    57.1%
    0
    0%
    8
    72.7%
    8
    72.7%
    5
    45.5%
    1
    11.1%
    10
    50%
    15
    19.7%
    White blood cells
    3
    100%
    7
    100%
    3
    75%
    10
    90.9%
    10
    90.9%
    9
    81.8%
    8
    88.9%
    20
    100%
    27
    35.5%
    Alanine aminotransferase (ALT)
    2
    66.7%
    4
    57.1%
    1
    25%
    3
    27.3%
    4
    36.4%
    4
    36.4%
    5
    55.6%
    11
    55%
    15
    19.7%
    Alkaline phosphatase
    2
    66.7%
    6
    85.7%
    3
    75%
    9
    81.8%
    8
    72.7%
    8
    72.7%
    6
    66.7%
    15
    75%
    20
    26.3%
    Amylase
    0
    0%
    0
    0%
    1
    25%
    1
    9.1%
    1
    9.1%
    0
    0%
    1
    11.1%
    1
    5%
    2
    2.6%
    Aspartate aminotransferase (AST)
    2
    66.7%
    3
    42.9%
    1
    25%
    5
    45.5%
    6
    54.5%
    5
    45.5%
    6
    66.7%
    8
    40%
    13
    17.1%
    Bilirubin (total)
    0
    0%
    2
    28.6%
    0
    0%
    1
    9.1%
    0
    0%
    2
    18.2%
    0
    0%
    4
    20%
    4
    5.3%
    Creatinine
    3
    100%
    7
    100%
    3
    75%
    10
    90.9%
    11
    100%
    10
    90.9%
    9
    100%
    18
    90%
    25
    32.9%
    Hypercalcemia
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    1
    5%
    2
    2.6%
    Hyperglycemia
    3
    100%
    7
    100%
    3
    75%
    9
    81.8%
    7
    63.6%
    10
    90.9%
    7
    77.8%
    16
    80%
    23
    30.3%
    Hyperkalemia
    0
    0%
    0
    0%
    2
    50%
    1
    9.1%
    4
    36.4%
    2
    18.2%
    3
    33.3%
    6
    30%
    9
    11.8%
    Hypermagnesemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    10%
    2
    2.6%
    Hypernatremia
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    2
    22.2%
    2
    10%
    2
    2.6%
    Hypoalbuminemia
    2
    66.7%
    2
    28.6%
    3
    75%
    5
    45.5%
    5
    45.5%
    7
    63.6%
    4
    44.4%
    10
    50%
    13
    17.1%
    Hypocalcemia
    2
    66.7%
    2
    28.6%
    2
    50%
    5
    45.5%
    5
    45.5%
    5
    45.5%
    5
    55.6%
    9
    45%
    12
    15.8%
    Hypoglycemia
    1
    33.3%
    1
    14.3%
    1
    25%
    1
    9.1%
    3
    27.3%
    0
    0%
    0
    0%
    3
    15%
    6
    7.9%
    Hypokalemia
    2
    66.7%
    2
    28.6%
    0
    0%
    0
    0%
    1
    9.1%
    1
    9.1%
    0
    0%
    5
    25%
    6
    7.9%
    Hypomagnesemia
    1
    33.3%
    0
    0%
    2
    50%
    1
    9.1%
    3
    27.3%
    1
    9.1%
    0
    0%
    3
    15%
    6
    7.9%
    Hyponatremia
    3
    100%
    2
    28.6%
    3
    75%
    6
    54.5%
    3
    27.3%
    3
    27.3%
    2
    22.2%
    6
    30%
    8
    10.5%
    Hypophosphatemia
    0
    0%
    1
    14.3%
    1
    25%
    4
    36.4%
    0
    0%
    3
    27.3%
    2
    22.2%
    6
    30%
    6
    7.9%
    Liapase
    1
    33.3%
    1
    14.3%
    1
    25%
    2
    18.2%
    2
    18.2%
    2
    18.2%
    2
    22.2%
    5
    25%
    6
    7.9%
    4. Secondary Outcome
    Title Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
    Description Vital signs evaluation included sitting diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse rate. Suggest text: Vital signs categorical summary included: 1)SBP>150mmHg or DBP>100mmHg; 2)SBP>200mmHg or DBP>110mmHg; 3)SBP increase >=20 and <40mmHg; 4)SBP increase >=40 and <60mmHg; 5)SBP increase>=60mmHg; 6)DBP increase >=10 and <20mmHg; 7)DBP increase >=20 and <30mmHg; 8)DBP increase >=30mmHg; 9)pulse rate>120bpm; 10)pulse rate<50bpm.
    Time Frame From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 4 11 11 11 9 20 27
    Maximum on-study SBP>150 or DBP>100
    1
    33.3%
    1
    14.3%
    0
    0%
    2
    18.2%
    2
    18.2%
    2
    18.2%
    1
    11.1%
    4
    20%
    5
    6.6%
    Maximum on-study SBP >200 or DBP>110
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Maximum increase from Baseline SBP>=20 and SBP<40
    0
    0%
    0
    0%
    0
    0%
    5
    45.5%
    0
    0%
    2
    18.2%
    1
    11.1%
    4
    20%
    4
    5.3%
    Maximum increase from Baseline SBP>=40 and SBP<60
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    27.3%
    0
    0%
    0
    0%
    1
    5%
    3
    3.9%
    Maximum increase from Baseline SBP>=60
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Maximum increase from Baseline DBP>=10 and DPB<20
    0
    0%
    0
    0%
    1
    25%
    3
    27.3%
    5
    45.5%
    1
    9.1%
    4
    44.4%
    6
    30%
    9
    11.8%
    Maximum increase from Baseline DBP>= 20 and DBP<30
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    11.1%
    1
    5%
    1
    1.3%
    Maximum increase from Baseline DBP >=30
    0
    0%
    1
    14.3%
    0
    0%
    1
    9.1%
    1
    9.1%
    0
    0%
    0
    0%
    0
    0%
    1
    1.3%
    Maximum on-study pulse rate (bpm) >120
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Maximum on-study pulse rate (bpm) <50
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    5. Secondary Outcome
    Title Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9
    Description Carbohydrate antigen 19-9 (Ca19-9) is a clinical pharmacodynamic (PD) marker associated with metastatic pancreatic ductal adenocarcinoma (mPDAC).
    Time Frame From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 3 8 9 7 6 14 21
    Count of Participants [Participants]
    3
    100%
    5
    71.4%
    0
    0%
    7
    63.6%
    6
    54.5%
    5
    45.5%
    3
    33.3%
    10
    50%
    15
    19.7%
    6. Secondary Outcome
    Title Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9
    Description Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
    Time Frame From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 3 8 9 7 6 14 21
    Count of Participants [Participants]
    1
    33.3%
    4
    57.1%
    0
    0%
    5
    45.5%
    6
    54.5%
    4
    36.4%
    2
    22.2%
    5
    25%
    10
    13.2%
    7. Secondary Outcome
    Title Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9
    Description Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
    Time Frame From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 3 8 9 7 6 14 21
    Count of Participants [Participants]
    0
    0%
    1
    14.3%
    0
    0%
    3
    27.3%
    4
    36.4%
    1
    9.1%
    1
    11.1%
    4
    20%
    8
    10.5%
    8. Secondary Outcome
    Title Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9
    Description Ca19-9 is a clinical PD marker associated with metastatic mPDAC.
    Time Frame From screening to the end of treatment/withdrawal visit (up to 63 days from last dose of investigational product).

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 3 8 9 7 6 14 21
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    0
    0%
    1
    5%
    2
    2.6%
    9. Secondary Outcome
    Title Objective Response Rate
    Description Percentage of participants who achieved objective response (OR) based on investigator assessment is presented. OR is defined as a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Objective response rate (ORR) was defined as the percentage of participants with a best overall response of CR or PR relative to all anti-tumor evaluable participants.
    Time Frame From screening to 365 days from the last dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product, had a baseline tumor assessment and at least 1 on-treatment tumor assessment prior to any new anti-cancer therapies. Results for groups with a small sample size should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 0 0 0 0 7 0 0 16 23
    Number (95% Confidence Interval) [Percentage of participants]
    28.6
    953.3%
    6.3
    90%
    13.0
    325%
    10. Secondary Outcome
    Title Duration of Response
    Description The duration of response was defined as the time from the first documentation of objective tumor response (CR or PR) to the first documentation of disease progression or to death due to any cause, whichever occurred first. Disease progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 mm.
    Time Frame From screening to 365 days from the last dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product, had a baseline tumor assessment and at least 1 on-treatment tumor assessment prior to any new anti-cancer therapies. Results for groups with a small sample size should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 0 0 0 0 7 0 0 16 23
    Median (95% Confidence Interval) [Months]
    NA
    7.4
    7.4
    11. Secondary Outcome
    Title Progression Free Survival
    Description The progression free survival (PFS) was defined as the time from the date of first dose to the date of the first documentation of objective tumor progression as per RECIST v1.1 or death due to any cause in the absence of documented progression disease, whichever occurred first.
    Time Frame From screening to 365 days from the last dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product, had a baseline tumor assessment and at least 1 on-treatment tumor assessment prior to any new anti-cancer therapies. Results for groups with a small sample size should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 4 11 11 11 9 20 27
    Median (95% Confidence Interval) [Months]
    9.1
    9.5
    1.7
    3.5
    5.5
    5.3
    1.8
    3.8
    5.3
    12. Secondary Outcome
    Title Six-month Progression-free Survival Rate (6m-PFSR)
    Description 6m-PFS was defined as PFS status (progression free and alive, or not) at Month 6. It was summarized as a product limit estimator based on the Kaplan-Meier method to account for censored events.
    Time Frame From screening to 6 months after first dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of either investigational product, had a baseline tumor assessment and at least 1 on-treatment tumor assessment prior to any new anti-cancer therapies. Results for groups with a small sample size should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 4 11 11 11 9 20 27
    Number (95% Confidence Interval) [Percentage of participants]
    66.7
    2223.3%
    66.7
    952.9%
    NA
    NaN
    30.0
    272.7%
    36.4
    330.9%
    27.3
    248.2%
    25.0
    277.8%
    36.2
    181%
    36.5
    48%
    13. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from the date of first dose to the date of death due to any cause. Following the end of treatment visit, survival status was collected in all participants every month until 12 months (365 days) had elapsed from the last dose of investigational product.
    Time Frame From screening to 365 days from the last dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    Participants who received study treatment, had adequate baseline assessments and at least 1 on-treatment tumor assessment prior to any new anti-cancer therapies were evaluable for anti-tumor activity. Results for groups with a small sample size should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 7 4 11 11 11 9 20 27
    Median (95% Confidence Interval) [Months]
    9.8
    23.4
    3.3
    7.2
    9.9
    5.3
    7.2
    11.4
    12.1
    14. Secondary Outcome
    Title Number of Participants With Positive p16
    Description p16 is a tumor suppressor protein which plays an important role in cell cycle regulation. The analysis of biomarker p16 expression might aid in the identification of patient subpopulations most likely to benefit from treatment. The results from p16 expression testing by immunohistochemistry (IHC) was used for sensitivity analyses. (a) and (b) :p16 cutoff utilizing the optimal cut point identified by the ORC analysis for the OS (a) or PFS (b) and the p16 positive tumor cells.
    Time Frame From Day-2 to up to 63 days from last dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment and met the criteria for measuring p16.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 5 4 10 10 10 9 19 26
    p16(a)
    1
    33.3%
    2
    28.6%
    0
    0%
    5
    45.5%
    7
    63.6%
    6
    54.5%
    3
    33.3%
    10
    50%
    15
    19.7%
    p16(b)
    1
    33.3%
    1
    14.3%
    0
    0%
    4
    36.4%
    6
    54.5%
    4
    36.4%
    1
    11.1%
    9
    45%
    13
    17.1%
    15. Secondary Outcome
    Title Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining)
    Description Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses.
    Time Frame From Day-2 to up to 63 days from last dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment and met the criteria for measuring Rb.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 5 4 10 10 10 9 19 26
    Mean (Standard Deviation) [Percentage of positive cell]
    88.3
    (7.64)
    80.0
    (29.79)
    68.8
    (23.23)
    91.1
    (10.24)
    90.5
    (18.77)
    92.5
    (8.25)
    82.2
    (32.70)
    92.4
    (19.10)
    91.7
    (19.54)
    16. Secondary Outcome
    Title Rb H-score Nuclear Staining
    Description Rb is a tumor suppressor protein that is dysfunctional in several major cancers. The results from Rb expression testing by IHC was used for sensitivity analyses. The H-score is a method of assessing the extent of nuclear immunoreactivity, applicable to steroid receptors. The score is obtained by the formula: 3*percentage of strongly staining nuclei + 2*percentage of moderately staining nuclei + percentage of weakly staining nuclei, giving the range of 0 to 300
    Time Frame From Day-2 to up to 63 days from last dose of investigational product

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment and met the criteria for measuring Rb.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all participants from the MTD cohort.
    Measure Participants 3 5 4 10 10 10 9 19 26
    Mean (Standard Deviation) [Scores on a scale]
    158.3
    (34.03)
    154.0
    (65.9)
    108.8
    (43.28)
    166.7
    (32.88)
    176.0
    (47.31)
    172.5
    (32.17)
    145.6
    (70.51)
    187.9
    (52.37)
    185.4
    (51.63)
    17. Secondary Outcome
    Title Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax)
    Description The palbociclib multiple dose maximum plasma concentration(Cmax) was observed directly from data.
    Time Frame Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic (PK) of interest and had no major protocol deviations affecting PK assessment. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts The overall participants with dose normalized to 125 mg/m^2
    Measure Participants 2 6 3 6 7 10 8 15 57
    Geometric Mean (Geometric Coefficient of Variation) [nanogram per milli liter (ng/mL)]
    NA
    (NA)
    90.68
    (24)
    57.30
    (56)
    98.79
    (46)
    64.55
    (23)
    48.05
    (54)
    53.65
    (25)
    70.14
    (43)
    90.44
    (39)
    18. Secondary Outcome
    Title Palbociclib Multiple Dose Time for Cmax (Tmax)
    Description The palbociclib multiple dose time for Cmax (Tmax) was observed directly from data.
    Time Frame Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic (PK) of interest and had no major protocol deviations affecting PK assessment. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 2 6 3 6 7 10 8 15 57
    Median (Full Range) [hour(hr)]
    4.93
    5.00
    3.90
    5.83
    4.50
    5.00
    6.01
    4.17
    5.05
    19. Secondary Outcome
    Title Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ)
    Description The palbociclib area under the plasma concentration-time curve for dosing interval τ (AUCτ) was observed directly from data.
    Time Frame Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic (PK) of interest and had no major protocol deviations affecting PK assessment. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 2 6 3 6 7 10 8 15 57
    Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milli liter (ng.hr/mL)]
    NA
    (NA)
    1497
    (18)
    897.4
    (36)
    1867
    (40)
    1169
    (21)
    767.9
    (42)
    967.7
    (26)
    1251
    (38)
    1569
    (34)
    20. Secondary Outcome
    Title Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough)
    Description The palbociclib multiple dose trough plasma concentration (Ctrough) was observed directly from data.
    Time Frame Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic (PK) of interest and had no major protocol deviations affecting PK assessment. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 2 6 3 6 6 10 8 15 56
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    NA
    (NA)
    43.42
    (34)
    26.84
    (19)
    71.82
    (42)
    41.92
    (11)
    22.34
    (37)
    30.66
    (34)
    34.89
    (34)
    48.51
    (38)
    21. Secondary Outcome
    Title Palbociclib Multiple Dose Apparent Clearance (CL/F)
    Description The palbociclib multiple dose apparent clearance (CL/F) was observed directly from data.
    Time Frame Cycle 1 Day 13 at 0 (pre-dose), 2, 4, 6, 8 and 24 hours post palbociclib dose, and pre-dose on Cycle 2, Days 1 and 15.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic (PK) of interest and had no major protocol deviations affecting PK assessment. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 2 6 3 6 7 10 8 15 57
    Geometric Mean (Geometric Coefficient of Variation) [liter per hour (L/hr)]
    NA
    (NA)
    66.67
    (18)
    83.63
    (36)
    64.52
    (40)
    85.42
    (21)
    97.67
    (42)
    77.62
    (26)
    79.95
    (38)
    79.35
    (34)
    22. Secondary Outcome
    Title Nab-P Cmax
    Description The nab-P Cmax on Cycle 1 Day -1 and Day 13 were observed directly from data.
    Time Frame Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who were treated. Number analyzed for each category represents the number of participants with Nab-P Cmax data for each time point. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 3 7 3 11 11 11 8 19 76
    Day -1
    1208
    (250)
    1595
    (61)
    1869
    (47)
    2733
    (127)
    3396
    (117)
    3271
    (113)
    1851
    (196)
    3054
    (129)
    2827
    (121)
    Day 13
    NA
    (NA)
    1532
    (146)
    2316
    (56)
    1265
    (219)
    3073
    (57)
    2821
    (93)
    1266
    (167)
    3448
    (73)
    2487
    (111)
    23. Secondary Outcome
    Title Nab-P Tmax
    Description The nab-P Tmax on Day -1 and Day 13 were observed directly from data.
    Time Frame Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who were treated. Number analyzed for each category represents the number of participants with Nab-P Tmax data for each time point. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 3 7 4 11 11 11 9 20 76
    Day -1
    0.500
    1.00
    1.00
    0.567
    0.600
    0.500
    0.775
    0.500
    0.517
    Day 13
    0.592
    0.583
    0.500
    1.00
    0.517
    0.500
    0.575
    0.533
    0.542
    24. Secondary Outcome
    Title Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast)
    Description The nab-P area under the plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) on Day -1 and Day 13 were observed directly from data.
    Time Frame Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who were treated. Number analyzed for each category represents the number of participants with Nab-P AUClast data for each time point. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 3 7 4 11 11 11 9 20 76
    Day -1
    2071
    (127)
    3501
    (48)
    3489
    (33)
    4291
    (70)
    4895
    (54)
    4472
    (59)
    2632
    (146)
    3942
    (60)
    4211
    (70)
    Day 13
    NA
    (NA)
    2592
    (70)
    4096
    (64)
    2894
    (133)
    4095
    (32)
    4183
    (44)
    2071
    (100)
    4269
    (52)
    3812
    (67)
    25. Secondary Outcome
    Title Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
    Description The nab-P area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUCinf) on Day -1 and Day 13 observed directly from data.
    Time Frame Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who were treated. Number analyzed for each category represents the number of participants with Nab-P AUCinf data for each time point. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 3 7 4 11 11 11 9 20 76
    Day -1
    NA
    (NA)
    3851
    (50)
    3780
    (30)
    4157
    (48)
    5387
    (54)
    5132
    (56)
    4116
    (34)
    4760
    (49)
    4977
    (46)
    Day 13
    NA
    (NA)
    NA
    (NA)
    4590
    (60)
    3349
    (67)
    4493
    (29)
    4482
    (46)
    2206
    (118)
    5135
    (38)
    4447
    (55)
    26. Secondary Outcome
    Title Nab-P Terminal Plasma Elimination Half-life (t1/2)
    Description The nab-P t1/2 on Day -1 and Day 13 were observed directly from data.
    Time Frame Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who were treated. Number analyzed for each category represents the number of participants with Nab-P t1/2 data for each time point. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 3 7 4 11 11 11 9 20 76
    Day -1
    16.95
    11.10
    12.00
    15.25
    12.85
    16.10
    15.80
    14.45
    14.50
    Day 13
    15.20
    17.65
    18.60
    16.40
    17.10
    13.80
    14.35
    14.40
    15.20
    27. Secondary Outcome
    Title Nab-P Clearance (CL)
    Description The nab-P clearance on Day -1 and Day 13 were observed directly from data.
    Time Frame Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who were treated. Number analyzed for each category represents the number of participants with Nab-P clearance data for each time point. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 3 7 4 11 11 11 9 20 76
    Day -1
    NA
    (NA)
    42.05
    (56)
    60.94
    (36)
    41.69
    (51)
    37.77
    (46)
    44.02
    (51)
    42.39
    (34)
    47.39
    (48)
    43.63
    (46)
    Day 13
    NA
    (NA)
    NA
    (NA)
    52.34
    (65)
    50.14
    (78)
    46.37
    (33)
    47.89
    (48)
    76.34
    (131)
    44.92
    (40)
    49.35
    (57)
    28. Secondary Outcome
    Title Nab-P Volume of Distribution (Vz)
    Description The nab-P on Day -1 and Day 13 were observed directly from data.
    Time Frame Prior to nab-P infusion and at 30 min (end of infusion), 1, 2, 4, 6, 8, 24, and 48 hours post the start of paclitaxel infusion on Day -2 and 13 of Cycle 1.

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all enrolled participants treated who were treated. Number analyzed for each category represents the number of participants with Nab-P volume of distribution data for each time point. Results for groups with a small sample size could be misleading due to inter-individual variability and should be interpreted with caution.
    Arm/Group Title DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 Overall Participants With Dose Normalized to 125 mg/m^2.
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The overall participants with dose normalized to 125 mg/m^2.
    Measure Participants 3 7 4 11 11 11 9 20 76
    Day -1
    NA
    (NA)
    709.1
    (44)
    1140
    (44)
    891.3
    (37)
    701.6
    (46)
    943.3
    (56)
    904.5
    (39)
    950.8
    (51)
    873.3
    (46)
    Day 13
    NA
    (NA)
    NA
    (NA)
    1271
    (106)
    1235
    (69)
    1070
    (71)
    927.2
    (32)
    1220
    (57)
    971.1
    (52)
    1036
    (52)

    Adverse Events

    Time Frame From the signing of informed consent up to 56 days after the last administration of the investigational product, or 365 days from the first dose of investigational product, whichever is later.
    Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.
    Arm/Group Title DL1 Palbociclib 75mg / Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg / Nab-Paclitaxel 100mg/m^2 DL2B Palbociclib 75mg / Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg / Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Arm/Group Description Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the starting dose level (DL), participants received palbociclib 75 milligrams (mg) daily for 3 weeks of each 28-day cycle and nab-P 100 milligrams per square miter (mg/m^2) weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2A, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 2B, participants received palbociclib 75mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3A, participants received palbociclib 125mg daily for 3 weeks of each 28-day cycle and nab-P 100mg/m^2 weekly for 3 weeks out of each 28-day cycle. Consecutive cohorts of participants received escalating doses of oral palbociclib in combination with intravenous nab-P in 28-day cycles. This was the escalated DL 3B, participants received palbociclib 100mg daily for 3 weeks of each 28-day cycle and nab-P 125mg/m^2 weekly for 3 weeks out of each 28-day cycle. This was the modified dose regimen 1 (MDR1), participants received palbociclib 75mg once daily on Days 1-21 of each 28-day cycle, plus nab-P 125mg/m^2 biweekly in each 28-day cycle. This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m^2 biweekly in each 28-day cycle. The estimated maximum tolerated dose (MTD) was the DL associated with <33% of 9 participants experiencing a DLT. The MTD was estimated to be palbociclib 100mg once daily on Days 1-21 plus nab-paclitaxel 125mg/m^2 weekly for 3 weeks of a 28-day cycle based on data from the dose escalation cohorts. The combined DL3B+MTD cohort was 7 first line participants from the DL3B cohort and all patients from the MTD cohort.
    All Cause Mortality
    DL1 Palbociclib 75mg / Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg / Nab-Paclitaxel 100mg/m^2 DL2B Palbociclib 75mg / Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg / Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 1/7 (14.3%) 3/4 (75%) 2/11 (18.2%) 3/11 (27.3%) 5/11 (45.5%) 2/9 (22.2%) 6/20 (30%) 7/27 (25.9%)
    Serious Adverse Events
    DL1 Palbociclib 75mg / Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg / Nab-Paclitaxel 100mg/m^2 DL2B Palbociclib 75mg / Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg / Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/3 (66.7%) 4/7 (57.1%) 3/4 (75%) 4/11 (36.4%) 6/11 (54.5%) 9/11 (81.8%) 2/9 (22.2%) 12/20 (60%) 15/27 (55.6%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Neutropenia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Anaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 2 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Cardiac disorders
    Cardiac arrest 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Myocardial infarction 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 2/20 (10%) 2 2/27 (7.4%) 2
    Ascites 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Colitis 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Diarrhoea 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 2 1/27 (3.7%) 2
    Duodenal ulcer 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Gastric haemorrhage 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Gastric ulcer 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Ileus 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Intestinal obstrucion 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Intestinal perforation 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Nausea 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Pancreatitis acute 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Upper gastrointestinal haemorrhage 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    vomiting 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 2 1/27 (3.7%) 2
    General disorders
    Asthenia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Chest pain 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Disease progression 0/3 (0%) 0 1/7 (14.3%) 1 1/4 (25%) 1 0/11 (0%) 0 1/11 (9.1%) 1 4/11 (36.4%) 4 0/9 (0%) 0 1/20 (5%) 1 2/27 (7.4%) 2
    Mucosal inflammation 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Pain 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Pyrexia 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Hepatobiliary disorders
    Bile duct obstruction 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 2/20 (10%) 2 2/27 (7.4%) 2
    Cholangitis 0/3 (0%) 0 2/7 (28.6%) 2 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Hyperbilirubinaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Infections and infestations
    Escherichia infection 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Gastritis bacterial 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Influenza 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Liver abscess 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Pneumonia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 2/27 (7.4%) 2
    Sepsis 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Bacteraemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Empyema 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Injury, poisoning and procedural complications
    Overdose 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Investigations
    Blood bilirubin increased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Liver function test increased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Neutrophil count decreased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    White blood cell count decreased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Metabolism and nutrition disorders
    Hypocalcaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Hypoglycaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Hypokalaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 2/20 (10%) 2 2/27 (7.4%) 2
    Musculoskeletal and connective tissue disorders
    Back pain 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Muscular weakness 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasm progression 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Nervous system disorders
    Migraine 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Seizure 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Syncope 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Product Issues
    Device occlusion 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Pleural effusion 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Pneumothorax 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Respiratory failure 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Vascular disorders
    Deep vein thrombosis 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Other (Not Including Serious) Adverse Events
    DL1 Palbociclib 75mg / Nab-Paclitaxel 100mg/m^2 DL2A Palbociclib 100mg / Nab-Paclitaxel 100mg/m^2 DL2B Palbociclib 75mg / Nab-Paclitaxel 125mg/m^2 DL3A Palbociclib 125mg / Nab-Paclitaxel 100mg/m^2 DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 MTD+DL3B
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 7/7 (100%) 4/4 (100%) 11/11 (100%) 10/11 (90.9%) 11/11 (100%) 9/9 (100%) 20/20 (100%) 27/27 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/3 (33.3%) 1 2/7 (28.6%) 5 2/4 (50%) 3 5/11 (45.5%) 11 3/11 (27.3%) 6 6/11 (54.5%) 11 1/9 (11.1%) 1 9/20 (45%) 17 11/27 (40.7%) 22
    Febrile neutropenia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Leukopenia 0/3 (0%) 0 1/7 (14.3%) 10 0/4 (0%) 0 2/11 (18.2%) 6 0/11 (0%) 0 2/11 (18.2%) 3 2/9 (22.2%) 5 2/20 (10%) 11 2/27 (7.4%) 11
    Lymphopenia 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Neutropenia 2/3 (66.7%) 6 5/7 (71.4%) 37 1/4 (25%) 2 9/11 (81.8%) 57 7/11 (63.6%) 21 5/11 (45.5%) 10 6/9 (66.7%) 19 16/20 (80%) 63 20/27 (74.1%) 78
    Thrombocytopenia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 3 1/11 (9.1%) 6 1/11 (9.1%) 1 0/9 (0%) 0 5/20 (25%) 12 6/27 (22.2%) 18
    Iron deficiency anaemia 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Cardiac disorders
    Sinus tachycardia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Tachycardia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Eye disorders
    Eye haemorrhage 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Vision blurred 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Visual impairment 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Gastrointestinal disorders
    Abdominal distension 1/3 (33.3%) 1 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Abdominal pain 1/3 (33.3%) 1 3/7 (42.9%) 6 0/4 (0%) 0 1/11 (9.1%) 1 2/11 (18.2%) 5 4/11 (36.4%) 9 5/9 (55.6%) 5 4/20 (20%) 6 5/27 (18.5%) 9
    Abdominal pain lower 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Abdominal pain upper 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 4/11 (36.4%) 4 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Anal fistula 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Ascites 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 3/11 (27.3%) 4 1/9 (11.1%) 1 2/20 (10%) 2 2/27 (7.4%) 2
    Constipation 0/3 (0%) 0 1/7 (14.3%) 2 1/4 (25%) 1 2/11 (18.2%) 3 2/11 (18.2%) 2 3/11 (27.3%) 4 1/9 (11.1%) 1 7/20 (35%) 8 8/27 (29.6%) 9
    Dental caries 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Diarrhoea 1/3 (33.3%) 1 6/7 (85.7%) 13 1/4 (25%) 1 2/11 (18.2%) 5 4/11 (36.4%) 6 5/11 (45.5%) 11 2/9 (22.2%) 3 9/20 (45%) 17 12/27 (44.4%) 22
    Dry mouth 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Dyspepsia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 1/11 (9.1%) 1 0/9 (0%) 0 3/20 (15%) 3 3/27 (11.1%) 3
    Eructation 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Faeces discoloured 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Flatulence 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 2/27 (7.4%) 2
    Gastrooesophageal reflux disease 1/3 (33.3%) 1 1/7 (14.3%) 2 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 1/9 (11.1%) 1 1/20 (5%) 1 2/27 (7.4%) 2
    Gingival bleeding 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Haematochezia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Haemorrhoidal haemorrhage 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Haemorrhoids 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Impaired gastric emptying 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Intestinal obstruction 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Mouth haemorrhage 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Nausea 0/3 (0%) 0 2/7 (28.6%) 7 1/4 (25%) 1 4/11 (36.4%) 5 5/11 (45.5%) 8 6/11 (54.5%) 9 4/9 (44.4%) 10 9/20 (45%) 12 13/27 (48.1%) 19
    Odynophagia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Oral pain 1/3 (33.3%) 1 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Small intestinal obstruction 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Stomatitis 1/3 (33.3%) 1 0/7 (0%) 0 1/4 (25%) 1 2/11 (18.2%) 4 1/11 (9.1%) 1 2/11 (18.2%) 3 1/9 (11.1%) 1 1/20 (5%) 1 2/27 (7.4%) 2
    Toothache 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Vomiting 1/3 (33.3%) 3 1/7 (14.3%) 2 1/4 (25%) 1 1/11 (9.1%) 1 6/11 (54.5%) 13 5/11 (45.5%) 7 3/9 (33.3%) 3 4/20 (20%) 6 9/27 (33.3%) 16
    General disorders
    Asthenia 1/3 (33.3%) 1 3/7 (42.9%) 11 1/4 (25%) 2 2/11 (18.2%) 6 3/11 (27.3%) 14 4/11 (36.4%) 6 2/9 (22.2%) 9 4/20 (20%) 18 7/27 (25.9%) 32
    Catheter site irritation 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Chills 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 2 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Early satiety 2/3 (66.7%) 2 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Fatigue 1/3 (33.3%) 1 0/7 (0%) 0 1/4 (25%) 2 2/11 (18.2%) 2 3/11 (27.3%) 4 3/11 (27.3%) 7 2/9 (22.2%) 2 7/20 (35%) 9 9/27 (33.3%) 12
    Influenza like illness 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 2 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 1/27 (3.7%) 2
    Malaise 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 2/27 (7.4%) 3
    Mucosal inflammation 0/3 (0%) 0 2/7 (28.6%) 2 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 3 2/27 (7.4%) 4
    Oedema peripheral 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 2/11 (18.2%) 2 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Pain 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 3/11 (27.3%) 3 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Peripheral swelling 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Pyrexia 2/3 (66.7%) 3 4/7 (57.1%) 10 1/4 (25%) 1 0/11 (0%) 0 1/11 (9.1%) 1 2/11 (18.2%) 2 1/9 (11.1%) 1 5/20 (25%) 9 6/27 (22.2%) 10
    Hepatobiliary disorders
    Bile duct obstruction 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Biliary dilatation 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Deficiency of bile secretion 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Hypertransaminasaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Ocular icterus 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Infections and infestations
    Bacterial infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Bronchitis 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Candida infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Escherichia infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 2/20 (10%) 3 2/27 (7.4%) 3
    Fungal infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Infected dermal cyst 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Influenza 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 2/11 (18.2%) 2 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Nail infection 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 2 1/27 (3.7%) 2
    Oral herpes 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Perinephric abscess 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Pneumonia 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Respiratory tract infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 1/20 (5%) 1 1/27 (3.7%) 1
    Septic shock 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Tooth infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Upper respiratory tract infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Urosepsis 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Wound infection 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Lumbar vertebral fracture 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Skin abrasion 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Investigations
    Activated partial thromboplastin time abnormal 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Activated partial thromboplastin time prolonged 0/3 (0%) 0 1/7 (14.3%) 2 0/4 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Alanine aminotransferase increased 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 5 0/9 (0%) 0 1/20 (5%) 2 1/27 (3.7%) 2
    Amylase increased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Aspartate aminotransferase increased 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 4 0/9 (0%) 0 1/20 (5%) 2 1/27 (3.7%) 2
    Blood alkaline phosphatase increased 0/3 (0%) 0 1/7 (14.3%) 4 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 6 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Blood bilirubin increased 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Blood creatinine increased 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 1/9 (11.1%) 1 1/20 (5%) 1 2/27 (7.4%) 2
    Gamma-glutamyltransferase increased 0/3 (0%) 0 1/7 (14.3%) 2 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Haemoglobin decreased 0/3 (0%) 0 1/7 (14.3%) 2 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Lipase increased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Liver function test increased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Lymphocyte count decreased 0/3 (0%) 0 1/7 (14.3%) 3 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 0/9 (0%) 0 4/20 (20%) 7 5/27 (18.5%) 9
    Neutrophil count decreased 1/3 (33.3%) 2 2/7 (28.6%) 6 0/4 (0%) 0 1/11 (9.1%) 4 2/11 (18.2%) 10 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 2 3/27 (11.1%) 12
    Platelet count decreased 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 2/27 (7.4%) 3
    Weight decreased 1/3 (33.3%) 1 1/7 (14.3%) 1 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    White blood cell count decreased 0/3 (0%) 0 1/7 (14.3%) 2 0/4 (0%) 0 4/11 (36.4%) 8 2/11 (18.2%) 3 2/11 (18.2%) 5 2/9 (22.2%) 4 5/20 (25%) 6 7/27 (25.9%) 9
    Metabolism and nutrition disorders
    Decreased appetite 1/3 (33.3%) 2 2/7 (28.6%) 6 1/4 (25%) 2 1/11 (9.1%) 1 4/11 (36.4%) 10 7/11 (63.6%) 14 5/9 (55.6%) 9 3/20 (15%) 8 7/27 (25.9%) 18
    Dehydration 2/3 (66.7%) 6 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 2/11 (18.2%) 2 1/11 (9.1%) 1 0/9 (0%) 0 3/20 (15%) 3 5/27 (18.5%) 5
    Hyperglycaemia 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 2 1/11 (9.1%) 5 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Hypoalbuminaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 2/20 (10%) 2 2/27 (7.4%) 2
    Hypocalcaemia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Hypokalaemia 1/3 (33.3%) 2 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 2/20 (10%) 2 2/27 (7.4%) 2
    Hypomagnesaemia 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 2/20 (10%) 2 3/27 (11.1%) 3
    Hyponatraemia 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Hypophosphataemia 0/3 (0%) 0 1/7 (14.3%) 5 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 3 1/27 (3.7%) 3
    Iron deficiency 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/3 (33.3%) 1 1/7 (14.3%) 1 0/4 (0%) 0 1/11 (9.1%) 5 2/11 (18.2%) 2 1/11 (9.1%) 1 1/9 (11.1%) 1 3/20 (15%) 3 5/27 (18.5%) 5
    Back pain 0/3 (0%) 0 3/7 (42.9%) 3 1/4 (25%) 1 0/11 (0%) 0 3/11 (27.3%) 3 2/11 (18.2%) 2 2/9 (22.2%) 15 1/20 (5%) 1 3/27 (11.1%) 3
    Muscle spasms 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Muscular weakness 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Musculoskeletal chest pain 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Musculoskeletal pain 0/3 (0%) 0 1/7 (14.3%) 6 1/4 (25%) 1 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Myalgia 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 2/11 (18.2%) 4 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Pain in extremity 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 2 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 2
    Pain in jaw 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Tumor pain 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Nervous system disorders
    Ageusia 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Burning sensation 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Dizziness 0/3 (0%) 0 1/7 (14.3%) 1 1/4 (25%) 1 0/11 (0%) 0 1/11 (9.1%) 1 2/11 (18.2%) 2 0/9 (0%) 0 2/20 (10%) 2 2/27 (7.4%) 2
    Dizziness postural 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Dysaesthesia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Dysgeusia 2/3 (66.7%) 3 3/7 (42.9%) 3 1/4 (25%) 1 0/11 (0%) 0 1/11 (9.1%) 2 1/11 (9.1%) 3 1/9 (11.1%) 1 0/20 (0%) 0 1/27 (3.7%) 2
    Headache 0/3 (0%) 0 0/7 (0%) 0 1/4 (25%) 1 2/11 (18.2%) 3 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 4/20 (20%) 7 4/27 (14.8%) 7
    Hypoaesthesia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Mental impairment 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Neuropathy peripheral 1/3 (33.3%) 1 2/7 (28.6%) 2 0/4 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 5 1/11 (9.1%) 2 0/9 (0%) 0 4/20 (20%) 6 6/27 (22.2%) 11
    Neurotoxicity 1/3 (33.3%) 1 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 4 2/11 (18.2%) 2 1/9 (11.1%) 1 4/20 (20%) 11 6/27 (22.2%) 15
    Paraesthesia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 3 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Peripheral motor neuropathy 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 2 1/27 (3.7%) 2
    Peripheral sensory neuropathy 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 1/11 (9.1%) 2 2/11 (18.2%) 2 1/11 (9.1%) 1 1/9 (11.1%) 1 2/20 (10%) 2 3/27 (11.1%) 3
    Semnolence 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Speech disorder 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Taste disorder 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 2/27 (7.4%) 2
    Psychiatric disorders
    Confusion state 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Insomnia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 3/11 (27.3%) 3 2/11 (18.2%) 2 0/9 (0%) 0 1/20 (5%) 1 3/27 (11.1%) 3
    Renal and urinary disorders
    Acute kidney injury 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Choluria 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Micturition disorder 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Cough 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 3/11 (27.3%) 3 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 3/20 (15%) 6 3/27 (11.1%) 6
    Dysphonia 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Dyspnoea 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 2 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 2/20 (10%) 2 2/27 (7.4%) 2
    Epistaxis 1/3 (33.3%) 1 1/7 (14.3%) 1 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 2/20 (10%) 3 3/27 (11.1%) 4
    Nasal congestion 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 2/11 (18.2%) 2 1/11 (9.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 2/20 (10%) 4 3/27 (11.1%) 5
    Oropharyngeal pain 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 2 0/11 (0%) 0 0/9 (0%) 0 2/20 (10%) 2 4/27 (14.8%) 4
    Pleural effusion 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Pneumonitis 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Productive cough 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Rhinitis allergic 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Rhinorrhoea 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 2 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 2/27 (7.4%) 2
    Wheezing 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Skin and subcutaneous tissue disorders
    Alopecia 1/3 (33.3%) 2 6/7 (85.7%) 6 1/4 (25%) 1 3/11 (27.3%) 3 4/11 (36.4%) 5 6/11 (54.5%) 10 3/9 (33.3%) 3 6/20 (30%) 8 9/27 (33.3%) 12
    Dermatitis acneiform 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 3 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 3
    Dry skin 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 0/9 (0%) 0 4/20 (20%) 4 5/27 (18.5%) 5
    Erythema 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Nail discolouration 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Nail toxicity 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Night sweats 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Onychomadesis 1/3 (33.3%) 1 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Pain of skin 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Palmar-plantar erythrodysaesthesia syndrome 1/3 (33.3%) 1 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 4 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Pruritus 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1
    Pruritus generalised 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Rash 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 2/11 (18.2%) 2 1/11 (9.1%) 1 2/11 (18.2%) 2 1/9 (11.1%) 1 5/20 (25%) 5 5/27 (18.5%) 5
    Rash macular 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Rash maculo-papular 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 2 1/27 (3.7%) 2
    Skin ulcer 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 0/27 (0%) 0
    Skin lesion 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 1/11 (9.1%) 1 0/11 (0%) 0 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 1
    Vascular disorders
    Deep vein thrombosis 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 2 1/9 (11.1%) 1 1/20 (5%) 1 1/27 (3.7%) 1
    Hot flush 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 1/9 (11.1%) 1 0/20 (0%) 0 0/27 (0%) 0
    Hypertension 0/3 (0%) 0 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 2/11 (18.2%) 5 1/11 (9.1%) 1 0/9 (0%) 0 0/20 (0%) 0 1/27 (3.7%) 4
    Hypotension 0/3 (0%) 0 1/7 (14.3%) 1 0/4 (0%) 0 1/11 (9.1%) 1 1/11 (9.1%) 1 1/11 (9.1%) 2 1/9 (11.1%) 1 2/20 (10%) 4 2/27 (7.4%) 4
    Orthostatic hypotension 1/3 (33.3%) 2 0/7 (0%) 0 0/4 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/11 (0%) 0 0/9 (0%) 0 1/20 (5%) 1 1/27 (3.7%) 1

    Limitations/Caveats

    The rationale for the study was supported on theoretical and preclinical grounds. However, based on emerging clinical data, the combination of palbociclib and nab-P was not to be further developed.

    More Information

    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.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 18007181021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT02501902
    Other Study ID Numbers:
    • A5481059
    • 2015-001307-31
    First Posted:
    Jul 17, 2015
    Last Update Posted:
    Apr 6, 2021
    Last Verified:
    Mar 1, 2021