Metastatic Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
Ibrance, palbociclib, Abraxane, nab-paclitaxel, pancreas,
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.
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.
Interventions
DRUGPalbociclib
Palbociclib oral dosing on Days 1 to 21 of each 28-day cycle.
DRUGNab-Paclitaxel
Nab-paclitaxel IV dosing on Days -2, 6, and 13 of Cycle 1, and on Days 1, 8, and 15 of subsequent cycles.
Sponsors
Celgene
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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 |
Countries
Spain, United States
Participant flow
Pre-assignment details
This was a multiple dose, dose escalation study of palbociclib in combination with nab-paclitaxel (nab-P), in sequential cohorts of adult participants.
Participants by arm
| Arm | Count |
|---|---|
| DL1 Palbociclib 75 mg/Nab-Paclitaxel 100 mg /m^2 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. | 3 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100mg/m^2 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. | 7 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 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. | 4 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100 mg/m^2 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. | 11 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 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. | 11 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 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. | 11 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 This was the MDR2, participants received palbociclib 75mg continuous dosing, once daily, plus nab-P 100mg/m\^2 biweekly in each 28-day cycle. | 9 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 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. | 20 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 4 | 4 | 10 | 10 | 11 | 7 | 15 |
| Overall Study | Study Terminated by Sponsor | 0 | 3 | 0 | 1 | 1 | 0 | 2 | 4 |
| Overall Study | Subject Refused Further Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | 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 | DL1 Palbociclib 75 mg/Nab-Paclitaxel 100 mg /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 |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized <18 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 18-44 | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Age, Customized 45-64 | 5 Participants | 3 Participants | 5 Participants | 6 Participants | 2 Participants | 7 Participants | 8 Participants | 9 Participants | 45 Participants |
| Age, Customized 65-75 | 1 Participants | 1 Participants | 5 Participants | 5 Participants | 1 Participants | 4 Participants | 1 Participants | 9 Participants | 27 Participants |
| Age, Customized >75 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 4 Participants | 11 Participants | 11 Participants | 3 Participants | 11 Participants | 8 Participants | 20 Participants | 74 Participants |
| Sex: Female, Male Female | 5 Participants | 1 Participants | 6 Participants | 5 Participants | 2 Participants | 3 Participants | 6 Participants | 6 Participants | 34 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants | 6 Participants | 1 Participants | 8 Participants | 3 Participants | 14 Participants | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 1 / 7 | 3 / 4 | 2 / 11 | 3 / 11 | 5 / 11 | 2 / 9 | 6 / 20 | 7 / 27 |
| other Total, other adverse events | 3 / 3 | 7 / 7 | 4 / 4 | 11 / 11 | 10 / 11 | 11 / 11 | 9 / 9 | 20 / 20 | 27 / 27 |
| serious Total, serious adverse events | 2 / 3 | 4 / 7 | 3 / 4 | 4 / 11 | 6 / 11 | 9 / 11 | 2 / 9 | 12 / 20 | 15 / 27 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities
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
Population: The analysis population included all participants who received at least 1 dose of either investigational product and met the measurable criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Dose Limiting Toxicities | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Dose Limiting Toxicities | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Dose Limiting Toxicities | 1 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Dose Limiting Toxicities | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Dose Limiting Toxicities | 1 Participants |
Secondary
Duration of Response
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Duration of Response | NA Months |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Duration of Response | 7.4 Months |
| MTD+DL3B | Duration of Response | 7.4 Months |
Secondary
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf)
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | NA ng.hr/mL | — |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | NA ng.hr/mL | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 3851 ng.hr/mL | Geometric Coefficient of Variation 50 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | NA ng.hr/mL | — |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 3780 ng.hr/mL | Geometric Coefficient of Variation 30 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | 4590 ng.hr/mL | Geometric Coefficient of Variation 60 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 4157 ng.hr/mL | Geometric Coefficient of Variation 48 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | 3349 ng.hr/mL | Geometric Coefficient of Variation 67 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 5387 ng.hr/mL | Geometric Coefficient of Variation 54 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | 4493 ng.hr/mL | Geometric Coefficient of Variation 29 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | 4482 ng.hr/mL | Geometric Coefficient of Variation 46 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 5132 ng.hr/mL | Geometric Coefficient of Variation 56 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | 2206 ng.hr/mL | Geometric Coefficient of Variation 118 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 4116 ng.hr/mL | Geometric Coefficient of Variation 34 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 4760 ng.hr/mL | Geometric Coefficient of Variation 49 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | 5135 ng.hr/mL | Geometric Coefficient of Variation 38 |
| MTD+DL3B | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day -1 | 4977 ng.hr/mL | Geometric Coefficient of Variation 46 |
| MTD+DL3B | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) | Day 13 | 4447 ng.hr/mL | Geometric Coefficient of Variation 55 |
Secondary
Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast)
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 2071 ng.hr/mL | Geometric Coefficient of Variation 127 |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | NA ng.hr/mL | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 3501 ng.hr/mL | Geometric Coefficient of Variation 48 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 2592 ng.hr/mL | Geometric Coefficient of Variation 70 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 3489 ng.hr/mL | Geometric Coefficient of Variation 33 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 4096 ng.hr/mL | Geometric Coefficient of Variation 64 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 4291 ng.hr/mL | Geometric Coefficient of Variation 70 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 2894 ng.hr/mL | Geometric Coefficient of Variation 133 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 4895 ng.hr/mL | Geometric Coefficient of Variation 54 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 4095 ng.hr/mL | Geometric Coefficient of Variation 32 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 4183 ng.hr/mL | Geometric Coefficient of Variation 44 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 4472 ng.hr/mL | Geometric Coefficient of Variation 59 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 2071 ng.hr/mL | Geometric Coefficient of Variation 100 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 2632 ng.hr/mL | Geometric Coefficient of Variation 146 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 3942 ng.hr/mL | Geometric Coefficient of Variation 60 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 4269 ng.hr/mL | Geometric Coefficient of Variation 52 |
| MTD+DL3B | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day -1 | 4211 ng.hr/mL | Geometric Coefficient of Variation 70 |
| MTD+DL3B | Nab-P Area Under the Plasma Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUClast) | Day 13 | 3812 ng.hr/mL | Geometric Coefficient of Variation 67 |
Secondary
Nab-P Clearance (CL)
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Clearance (CL) | Day -1 | NA liter per hour (L/hr) | — |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Clearance (CL) | Day 13 | NA liter per hour (L/hr) | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Clearance (CL) | Day -1 | 42.05 liter per hour (L/hr) | Geometric Coefficient of Variation 56 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Clearance (CL) | Day 13 | NA liter per hour (L/hr) | — |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day -1 | 60.94 liter per hour (L/hr) | Geometric Coefficient of Variation 36 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day 13 | 52.34 liter per hour (L/hr) | Geometric Coefficient of Variation 65 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Clearance (CL) | Day -1 | 41.69 liter per hour (L/hr) | Geometric Coefficient of Variation 51 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Clearance (CL) | Day 13 | 50.14 liter per hour (L/hr) | Geometric Coefficient of Variation 78 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day -1 | 37.77 liter per hour (L/hr) | Geometric Coefficient of Variation 46 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day 13 | 46.37 liter per hour (L/hr) | Geometric Coefficient of Variation 33 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day 13 | 47.89 liter per hour (L/hr) | Geometric Coefficient of Variation 48 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day -1 | 44.02 liter per hour (L/hr) | Geometric Coefficient of Variation 51 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Clearance (CL) | Day 13 | 76.34 liter per hour (L/hr) | Geometric Coefficient of Variation 131 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Clearance (CL) | Day -1 | 42.39 liter per hour (L/hr) | Geometric Coefficient of Variation 34 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day -1 | 47.39 liter per hour (L/hr) | Geometric Coefficient of Variation 48 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Clearance (CL) | Day 13 | 44.92 liter per hour (L/hr) | Geometric Coefficient of Variation 40 |
| MTD+DL3B | Nab-P Clearance (CL) | Day -1 | 43.63 liter per hour (L/hr) | Geometric Coefficient of Variation 46 |
| MTD+DL3B | Nab-P Clearance (CL) | Day 13 | 49.35 liter per hour (L/hr) | Geometric Coefficient of Variation 57 |
Secondary
Nab-P Cmax
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Cmax | Day 13 | NA ng/mL | — |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Cmax | Day -1 | 1208 ng/mL | Geometric Coefficient of Variation 250 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Cmax | Day 13 | 1532 ng/mL | Geometric Coefficient of Variation 146 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Cmax | Day -1 | 1595 ng/mL | Geometric Coefficient of Variation 61 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day 13 | 2316 ng/mL | Geometric Coefficient of Variation 56 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day -1 | 1869 ng/mL | Geometric Coefficient of Variation 47 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Cmax | Day -1 | 2733 ng/mL | Geometric Coefficient of Variation 127 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Cmax | Day 13 | 1265 ng/mL | Geometric Coefficient of Variation 219 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day -1 | 3396 ng/mL | Geometric Coefficient of Variation 117 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day 13 | 3073 ng/mL | Geometric Coefficient of Variation 57 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day -1 | 3271 ng/mL | Geometric Coefficient of Variation 113 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day 13 | 2821 ng/mL | Geometric Coefficient of Variation 93 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Cmax | Day -1 | 1851 ng/mL | Geometric Coefficient of Variation 196 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Cmax | Day 13 | 1266 ng/mL | Geometric Coefficient of Variation 167 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day -1 | 3054 ng/mL | Geometric Coefficient of Variation 129 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Cmax | Day 13 | 3448 ng/mL | Geometric Coefficient of Variation 73 |
| MTD+DL3B | Nab-P Cmax | Day 13 | 2487 ng/mL | Geometric Coefficient of Variation 111 |
| MTD+DL3B | Nab-P Cmax | Day -1 | 2827 ng/mL | Geometric Coefficient of Variation 121 |
Secondary
Nab-P Terminal Plasma Elimination Half-life (t1/2)
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.
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 16.95 hr |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 15.20 hr |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 11.10 hr |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 17.65 hr |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 12.00 hr |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 18.60 hr |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 15.25 hr |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 16.40 hr |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 12.85 hr |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 17.10 hr |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 13.80 hr |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 16.10 hr |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 14.35 hr |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 15.80 hr |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 14.45 hr |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 14.40 hr |
| MTD+DL3B | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day -1 | 14.50 hr |
| MTD+DL3B | Nab-P Terminal Plasma Elimination Half-life (t1/2) | Day 13 | 15.20 hr |
Secondary
Nab-P Tmax
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.
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Tmax | Day -1 | 0.500 hr |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Tmax | Day 13 | 0.592 hr |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Tmax | Day 13 | 0.583 hr |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Tmax | Day -1 | 1.00 hr |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day 13 | 0.500 hr |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day -1 | 1.00 hr |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Tmax | Day -1 | 0.567 hr |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Tmax | Day 13 | 1.00 hr |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day 13 | 0.517 hr |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day -1 | 0.600 hr |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day 13 | 0.500 hr |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day -1 | 0.500 hr |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Tmax | Day -1 | 0.775 hr |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Tmax | Day 13 | 0.575 hr |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day -1 | 0.500 hr |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Tmax | Day 13 | 0.533 hr |
| MTD+DL3B | Nab-P Tmax | Day 13 | 0.542 hr |
| MTD+DL3B | Nab-P Tmax | Day -1 | 0.517 hr |
Secondary
Nab-P Volume of Distribution (Vz)
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.
Population: 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 | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | NA L | — |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | NA L | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | NA L | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | 709.1 L | Geometric Coefficient of Variation 44 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | 1271 L | Geometric Coefficient of Variation 106 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | 1140 L | Geometric Coefficient of Variation 44 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | 891.3 L | Geometric Coefficient of Variation 37 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | 1235 L | Geometric Coefficient of Variation 69 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | 1070 L | Geometric Coefficient of Variation 71 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | 701.6 L | Geometric Coefficient of Variation 46 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | 927.2 L | Geometric Coefficient of Variation 32 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | 943.3 L | Geometric Coefficient of Variation 56 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | 904.5 L | Geometric Coefficient of Variation 39 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | 1220 L | Geometric Coefficient of Variation 57 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day -1 | 950.8 L | Geometric Coefficient of Variation 51 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Nab-P Volume of Distribution (Vz) | Day 13 | 971.1 L | Geometric Coefficient of Variation 52 |
| MTD+DL3B | Nab-P Volume of Distribution (Vz) | Day 13 | 1036 L | Geometric Coefficient of Variation 52 |
| MTD+DL3B | Nab-P Volume of Distribution (Vz) | Day -1 | 873.3 L | Geometric Coefficient of Variation 46 |
Secondary
Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9
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).
Population: The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 3 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 5 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 7 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 6 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 5 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 3 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 10 Participants |
| MTD+DL3B | Number of Participants With 20% Maximum Reduction From Baseline in Ca19-9 | 15 Participants |
Secondary
Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9
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).
Population: The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 4 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 5 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 6 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 4 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 2 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 5 Participants |
| MTD+DL3B | Number of Participants With 50% Maximum Reduction From Baseline in Ca19-9 | 10 Participants |
Secondary
Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9
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).
Population: The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 3 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 4 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 1 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 4 Participants |
| MTD+DL3B | Number of Participants With 70% Maximum Reduction From Baseline in Ca19-9 | 8 Participants |
Secondary
Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9
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).
Population: The analysis population included all participants who received at least 1 dose of investigational product and had at least 1 baseline biomarker assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 1 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 1 Participants |
| MTD+DL3B | Number of Participants With 90% Maximum Reduction From Baseline in Ca19-9 | 2 Participants |
Secondary
Number of Participants With Adverse Events
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
Population: The analysis population included all participants who received at least 1 dose of either investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality SAEs | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | All causality SAEs | 4 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 5 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 6 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 2 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 4 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality SAEs | 3 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 4 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 3 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 10 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality SAEs | 4 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 9 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 11 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 8 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 11 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 2 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 1 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 11 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 11 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 3 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality SAEs | 6 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 11 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 11 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality SAEs | 9 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 5 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 10 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 4 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 7 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 11 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 9 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality SAEs | 2 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 4 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 5 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 9 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality SAEs | 12 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related SAES | 6 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Adverse Events | All causality Grade 5 AEs | 1 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | Treatment-related Grade 5 AEs | 0 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | All causality Grade 5 AEs | 2 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | Treatment-related Grade 3 or 4 AEs | 27 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | All causality Grade 3 or 4 AEs | 27 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | Treatment-related SAES | 6 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | All causality SAEs | 15 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | Treatment-related treatment-emergent AEs | 27 Participants |
| MTD+DL3B | Number of Participants With Adverse Events | All causality treatment-emergent AEs | 27 Participants |
Secondary
Number of Participants With Laboratory Abnormalities
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).
Population: The analysis population included all participants who received at least 1 dose of either investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 1 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 1 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 1 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 3 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 2 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 3 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 2 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 6 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 2 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 4 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 2 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 3 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 2 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 7 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 2 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 4 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 3 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 3 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 4 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 3 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 2 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 2 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 2 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 3 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 2 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 3 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 3 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 2 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 5 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 2 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 8 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 10 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 10 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 11 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 9 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 6 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 9 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 5 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 3 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 5 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 4 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 9 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 10 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 10 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 11 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 10 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 10 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 8 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 4 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 8 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 1 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 6 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 11 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 1 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 7 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 4 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 5 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 5 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 3 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 1 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 3 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 3 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 2 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 8 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 5 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 1 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 10 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 9 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 7 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 4 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 5 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 2 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 2 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 3 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 11 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 1 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 2 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 9 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 3 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 1 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 11 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 5 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 10 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 7 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 6 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 3 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 6 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 2 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 5 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 4 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 8 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 8 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 5 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 8 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 2 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 7 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 2 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 2 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 9 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypokalemia | 5 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 16 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 1 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 6 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 15 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hyponatremia | 6 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Platelets | 10 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 6 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 11 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Anemia | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Creatinine | 18 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Lymphopenia | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 10 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Amylase | 1 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | White blood cells | 20 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 1 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypernatremia | 2 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 4 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 3 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Liapase | 5 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 9 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 3 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 2 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 8 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Platelets | 15 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Alkaline phosphatase | 20 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 2 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypoglycemia | 6 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Neutrophils (absolute) | 27 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Liapase | 6 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypokalemia | 6 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypophosphatemia | 6 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Lymphopenia | 27 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Aspartate aminotransferase (AST) | 13 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Amylase | 2 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hyperglycemia | 23 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 6 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 9 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Lymphocyte count increased | 0 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 2 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hyponatremia | 8 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypernatremia | 2 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hemoglobin increased | 1 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypoalbuminemia | 13 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | White blood cells | 27 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Bilirubin (total) | 4 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Alanine aminotransferase (ALT) | 15 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 12 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Anemia | 27 Participants |
| MTD+DL3B | Number of Participants With Laboratory Abnormalities | Creatinine | 25 Participants |
Secondary
Number of Participants With Positive p16
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
Population: 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 | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Positive p16 | p16(a) | 1 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Positive p16 | p16(b) | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Positive p16 | p16(a) | 2 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Positive p16 | p16(b) | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(a) | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(b) | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Positive p16 | p16(a) | 5 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Positive p16 | p16(b) | 4 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(a) | 7 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(b) | 6 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(b) | 4 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(a) | 6 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Positive p16 | p16(b) | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Positive p16 | p16(a) | 3 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(a) | 10 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Positive p16 | p16(b) | 9 Participants |
| MTD+DL3B | Number of Participants With Positive p16 | p16(a) | 15 Participants |
| MTD+DL3B | Number of Participants With Positive p16 | p16(b) | 13 Participants |
Secondary
Number of Participants With Vital Signs Data Meeting Pre-specified Criteria
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).
Population: The analysis population included all participants who received at least 1 dose of either investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 1 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 0 Participants |
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 1 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 1 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 5 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 3 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 1 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 2 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 3 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 1 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 2 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 5 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 1 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 2 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 2 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 0 Participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 4 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 1 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 1 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 1 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 6 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 4 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 4 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 1 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 0 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=20 and SBP<40 | 4 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP >=30 | 1 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=40 and SBP<60 | 3 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>=10 and DPB<20 | 9 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline SBP>=60 | 0 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) >120 | 0 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP >200 or DBP>110 | 0 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study pulse rate (bpm) <50 | 0 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum on-study SBP>150 or DBP>100 | 5 Participants |
| MTD+DL3B | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Maximum increase from Baseline DBP>= 20 and DBP<30 | 1 Participants |
Secondary
Objective Response Rate
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Objective Response Rate | 28.6 Percentage of participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Objective Response Rate | 6.3 Percentage of participants |
| MTD+DL3B | Objective Response Rate | 13.0 Percentage of participants |
Secondary
Overall Survival (OS)
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Overall Survival (OS) | 9.8 Months |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Overall Survival (OS) | 23.4 Months |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Overall Survival (OS) | 3.3 Months |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Overall Survival (OS) | 7.2 Months |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Overall Survival (OS) | 9.9 Months |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Overall Survival (OS) | 5.3 Months |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Overall Survival (OS) | 7.2 Months |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Overall Survival (OS) | 11.4 Months |
| MTD+DL3B | Overall Survival (OS) | 12.1 Months |
Secondary
Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ)
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.
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | NA nanogram*hour per milli liter (ng.hr/mL) | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 1497 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 18 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 897.4 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 36 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 1867 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 40 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 1169 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 21 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 767.9 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 42 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 967.7 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 26 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 1251 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 38 |
| MTD+DL3B | Palbociclib Area Under the Plasma Concentration-time Curve for Dosing Interval τ (AUCτ) | 1569 nanogram*hour per milli liter (ng.hr/mL) | Geometric Coefficient of Variation 34 |
Secondary
Palbociclib Multiple Dose Apparent Clearance (CL/F)
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.
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | NA liter per hour (L/hr) | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 66.67 liter per hour (L/hr) | Geometric Coefficient of Variation 18 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 83.63 liter per hour (L/hr) | Geometric Coefficient of Variation 36 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 64.52 liter per hour (L/hr) | Geometric Coefficient of Variation 40 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 85.42 liter per hour (L/hr) | Geometric Coefficient of Variation 21 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 97.67 liter per hour (L/hr) | Geometric Coefficient of Variation 42 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 77.62 liter per hour (L/hr) | Geometric Coefficient of Variation 26 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 79.95 liter per hour (L/hr) | Geometric Coefficient of Variation 38 |
| MTD+DL3B | Palbociclib Multiple Dose Apparent Clearance (CL/F) | 79.35 liter per hour (L/hr) | Geometric Coefficient of Variation 34 |
Secondary
Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax)
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.
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | NA nanogram per milli liter (ng/mL) | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 90.68 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 24 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 57.30 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 56 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 98.79 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 46 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 64.55 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 23 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 48.05 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 54 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 53.65 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 25 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 70.14 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 43 |
| MTD+DL3B | Palbociclib Multiple Dose Maximum Plasma Concentration (Cmax) | 90.44 nanogram per milli liter (ng/mL) | Geometric Coefficient of Variation 39 |
Secondary
Palbociclib Multiple Dose Time for Cmax (Tmax)
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.
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 4.93 hour(hr) |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 5.00 hour(hr) |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 3.90 hour(hr) |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 5.83 hour(hr) |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 4.50 hour(hr) |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 5.00 hour(hr) |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 6.01 hour(hr) |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Time for Cmax (Tmax) | 4.17 hour(hr) |
| MTD+DL3B | Palbociclib Multiple Dose Time for Cmax (Tmax) | 5.05 hour(hr) |
Secondary
Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough)
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.
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | NA ng/mL | — |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 43.42 ng/mL | Geometric Coefficient of Variation 34 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 26.84 ng/mL | Geometric Coefficient of Variation 19 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 71.82 ng/mL | Geometric Coefficient of Variation 42 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 41.92 ng/mL | Geometric Coefficient of Variation 11 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 22.34 ng/mL | Geometric Coefficient of Variation 37 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 30.66 ng/mL | Geometric Coefficient of Variation 34 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 34.89 ng/mL | Geometric Coefficient of Variation 34 |
| MTD+DL3B | Palbociclib Multiple Dose Trough Plasma Concentration(Ctrough) | 48.51 ng/mL | Geometric Coefficient of Variation 38 |
Secondary
Progression Free Survival
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Progression Free Survival | 9.1 Months |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Progression Free Survival | 9.5 Months |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Progression Free Survival | 1.7 Months |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Progression Free Survival | 3.5 Months |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Progression Free Survival | 5.5 Months |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Progression Free Survival | 5.3 Months |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Progression Free Survival | 1.8 Months |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Progression Free Survival | 3.8 Months |
| MTD+DL3B | Progression Free Survival | 5.3 Months |
Secondary
Rb H-score Nuclear Staining
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Rb H-score Nuclear Staining | 158.3 Scores on a scale | Standard Deviation 34.03 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Rb H-score Nuclear Staining | 154.0 Scores on a scale | Standard Deviation 65.9 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Rb H-score Nuclear Staining | 108.8 Scores on a scale | Standard Deviation 43.28 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Rb H-score Nuclear Staining | 166.7 Scores on a scale | Standard Deviation 32.88 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Rb H-score Nuclear Staining | 176.0 Scores on a scale | Standard Deviation 47.31 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Rb H-score Nuclear Staining | 172.5 Scores on a scale | Standard Deviation 32.17 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Rb H-score Nuclear Staining | 145.6 Scores on a scale | Standard Deviation 70.51 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Rb H-score Nuclear Staining | 187.9 Scores on a scale | Standard Deviation 52.37 |
| MTD+DL3B | Rb H-score Nuclear Staining | 185.4 Scores on a scale | Standard Deviation 51.63 |
Secondary
Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining)
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 88.3 Percentage of positive cell | Standard Deviation 7.64 |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 80.0 Percentage of positive cell | Standard Deviation 29.79 |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 68.8 Percentage of positive cell | Standard Deviation 23.23 |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 91.1 Percentage of positive cell | Standard Deviation 10.24 |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 90.5 Percentage of positive cell | Standard Deviation 18.77 |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 92.5 Percentage of positive cell | Standard Deviation 8.25 |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 82.2 Percentage of positive cell | Standard Deviation 32.7 |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 92.4 Percentage of positive cell | Standard Deviation 19.1 |
| MTD+DL3B | Retinoblastoma Protein (Rb) Percent Positive Cell (Nuclear Staining) | 91.7 Percentage of positive cell | Standard Deviation 19.54 |
Secondary
Six-month Progression-free Survival Rate (6m-PFSR)
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| DL1 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | 66.7 Percentage of participants |
| DL2A Palbociclib 100mg/Nab-Paclitaxel 100/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | 66.7 Percentage of participants |
| DL2B Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | NA Percentage of participants |
| DL3A Palbociclib 125mg/Nab-Paclitaxel 100mg/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | 30.0 Percentage of participants |
| DL3B Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | 36.4 Percentage of participants |
| MDR1 Palbociclib 75mg/Nab-Paclitaxel 125mg/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | 27.3 Percentage of participants |
| MDR2 Palbociclib 75mg/Nab-Paclitaxel 100mg/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | 25.0 Percentage of participants |
| MTD Palbociclib 100mg/Nab-Paclitaxel 125mg/m^2 | Six-month Progression-free Survival Rate (6m-PFSR) | 36.2 Percentage of participants |
| MTD+DL3B | Six-month Progression-free Survival Rate (6m-PFSR) | 36.5 Percentage of participants |