Advanced or Recurrent Solid Tumors, Breast Neoplasms, Ewing Sarcoma, Ovarian Cancer, Epithelial, Pancreas Cancer, Prostate Cancer, Small Cell Lung Carcinoma
Conditions
Keywords
BRCA1 Protein, BRCA2 Protein
Brief summary
This is a single-arm, open-label study to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of talazoparib in patients with advanced tumors with DNA-repair pathway deficiencies. There will be 2 parts to the study: a dose escalation phase in which the maximum tolerated dose will be defined, and a dose expansion phase.
Interventions
DRUGTalazoparib
Oral capsule with multiple dosage forms given once daily
Sponsors
Medivation, Inc.
Pfizer
Study design
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented, unresectable, locally advanced or metastatic solid tumor * Must have available archived tumor tissue (formalin-fixed paraffin-embedded) \[FFPE\]. * 18 years of age or older. * Have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) or increased CA-125 (ovarian cancer) or PSA (prostate cancer) and/or CA 19-9 (pancreatic cancer). * Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1. * Have adequate organ function * Able to take oral medications. * Willing and able to provide informed consent. * Sexually active patients must be willing to use an acceptable method of contraception. * Females of childbearing potential must have a negative serum pregnancy test at screening. * Willing and able to comply with all study procedures. Part 2 Dose Expansion Tumor Types: * Breast and ovarian cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 4 prior regimens for metastatic disease. * Prostate or pancreatic cancer patients with deleterious or pathogenic BRCA mutations who have received no more than 2 prior regimens for metastatic disease. * Small cell lung cancer (SCLC) patients who have received no more than one prior regimen for SCLC. * Ewing's sarcoma patients who have received no more than 3 prior regimens for metastatic disease.
Exclusion criteria
* Part 2 Expansion: Prior treatment with a PARP inhibitor. * Has history of central nervous system (CNS) metastasis. \* Exception: In patients with SCLC, history of adequately treated brain metastasis who do not require corticosteroids for management of CNS symptoms. * Has had major surgery within 28 days before Cycle 1, Day 1. * Has active peptic ulcer disease. * Active gastrointestinal tract disease with malabsorption syndrome. * Pregnant or breastfeeding at screening or planning to become pregnant (in each case, either oneself or one's partner) at any time during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Objective Response | From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2) | Objective response in participants was defined as the number of participants with complete response (CR) or partial response (PR) after treatment with talazoparib and maintained for at least 4 weeks (28 days) as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1. CR defined as disappearance of all non-nodal target lesions (where all target lesions were recorded with a length of 0 millimeter \[mm\] on the case report form \[CRF\]) and the reduction of the shortest diameter of all nodal lesions to less than \[\<\] 10 mm. PR was defined by a 30% or more decrease in the sum of the longest diameters (SLD) + sum of shortest diameters (SSD) of target lesions, taking as reference the baseline SLD+SSD. |
| Number of Participants With Best Overall Response | From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2) | Best overall response: best response (in the order of confirmed CR, confirmed PR, stable disease \[SD\] and progressive disease \[PD\]) among all overall response as RECIST 1.1, recorded from date of first dose of talazoparib until participant withdrew from study/data cut-off date, whichever earlier. CR defined as disappearance of all non-nodal target lesions (where all target lesions recorded with a length of 0 mm on the CRF) and the reduction of the shortest diameter of all nodal lesions to \< 10 mm. PR defined as at least a 30% decrease in sum of the diameters of target lesions, reference to baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study). |
| Progression-Free Survival (PFS) | Baseline, until PD or death due to any cause (maximum duration:1071 days for Part 1; 834 days for Part 2) | PFS was defined as the time (in weeks) from the date of first dose of study drug to the earlier date of the documented PD or death due to any cause. PD as per RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study). |
| Duration of Response | Baseline until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2) | Duration of response was defined as the time (in weeks) from the date of the first documented objective response confirmed at least 28 days later to the date of the first documented PD or date of death, whichever occurred first. PD as per RECIST version 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study). |
| Number of Participants With Stable Disease | Baseline, until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2) | SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study). |
| Part 1: Maximum Tolerated Dose (MTD) | Cycle 1 (Day 1 up to Day 42) | The MTD was defined as the highest dose at which no more than 1 of 6 participants experienced a Dose Limiting Toxicity (DLT). DLT defined as any of the following occurring during cycle 1 of part 1 of study, Hematologic toxicity: Any grade 4 or higher hematologic adverse event, Grade 3 thrombocytopenia associated with grade 2 or higher haemorrhage, Grade 3 thrombocytopenia or neutropenia that led to interruption of dosing for 5 or more days. Nonhematologic toxicity: grade 3 or higher laboratory AE which was asymptomatic and rapidly reversible adverse events (returned to baseline or to grade 1 or lower within 7 days), Grade 3 nausea, vomiting, or diarrhea that could be medically managed to grade 2 or lower with anti-emetics and/or anti-diarrheals within 24 hours, Grade 3 fatigue that improved to grade 2 or lower in 5 days or less, Alopecia. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. |
| Part 1: Recommended Part 2 Dose of Talazoparib | Baseline up to Cycle 50 (each cycle 28 days) | The Recommended dose of talazoparib for use in Part 2 was determined in Part 1 (dose escalation) on the basis of the totality of safety, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 35 | — |
| Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 | AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time. |
| Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1 | — |
| Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 | Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed. |
| Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35 | Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was influenced by the fraction absorbed. |
| Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35 | T1/2 is the time measured for the plasma concentration of talazoparib to decrease by one half. |
| Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | Part 1: Baseline up to 1071 days; Part 2: Baseline up to 834 days | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study (up to 1071 days for Part 1 and up to 834 days for Part 2) that were absent before treatment or that worsened relative to pre-treatment state. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35 | — |
| Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35 | — |
| Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1 | — |
| Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 | Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last). |
| Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1 | Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last). |
Countries
United Kingdom, United States
Participant flow
Pre-assignment details
Study was conducted in two parts: Part 1 was dose escalation phase (to determine the maximum tolerated dose \[MTD\]) and Part 2 was the dose expansion phase conducted at MTD determined in Part 1. Participants were different in both of the Parts.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Talazoparib 25 mcg/Day Participants received talazoparib capsules at a dose of 25 microgram per day (mcg/day) once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 3 |
| Part 1: Talazoparib 50 mcg/Day Participants received talazoparib capsules at a dose of 50 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 3 |
| Part 1: Talazoparib 100 mcg/Day Participants received talazoparib capsules at a dose of 100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 3 |
| Part 1: Talazoparib 200 mcg/Day Participants received talazoparib capsules at a dose of 200 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 3 |
| Part 1: Talazoparib 400 mcg/Day Participants received talazoparib capsules at a dose of 400 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 3 |
| Part 1: Talazoparib 600 mcg/Day Participants received talazoparib capsules at a dose of 600 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 6 |
| Part 1: Talazoparib 900 mcg/Day Participants received talazoparib capsules at a dose of 900 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 6 |
| Part 1: Talazoparib 1000 mcg/Day Participants received talazoparib capsules at a dose of 1000 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 6 |
| Part 1: Talazoparib 1100 mcg/Day Participants received talazoparib capsules at a dose of 1100 mcg/day once daily from Day 8 to 35 of Cycle 1 and thereafter once daily in each 28-day treatment cycle starting from Cycle 2 (up to a maximum of 50 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 6 |
| Part 2: Talazoparib (Breast Cancer) Participants with breast cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 12 |
| Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) Participants with ovarian/ peritoneal cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 11 |
| Part 2: Talazoparib (Pancreatic Cancer) Participants with pancreatic cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 10 |
| Part 2: Talazoparib (Ewing Cancer) Participants with ewing cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 12 |
| Part 2: Talazoparib (SCLC Cancer) Participants with SCLC cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 23 |
| Part 2: Talazoparib (Prostate Cancer) Participants with prostate cancer, received talazoparib capsules at the MTD as determined in Part 1 (1000 mcg/day), orally once daily in each 28-day treatment cycle (up to a maximum of 40 cycles) until documented disease progression or unacceptable toxicity, or until study discontinuation criteria were met. | 3 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Dose Escalation | Clinical Progression | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Progressive Disease | 2 | 2 | 3 | 2 | 1 | 5 | 5 | 3 | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part 2: Dose Expansion | Clinical Progression | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 2 | 0 |
| Part 2: Dose Expansion | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Part 2: Dose Expansion | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part 2: Dose Expansion | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 |
| Part 2: Dose Expansion | Progressive Disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 6 | 7 | 11 | 19 | 2 |
| Part 2: Dose Expansion | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part 2: Talazoparib (Prostate Cancer) | Part 2: Talazoparib (SCLC Cancer) | Part 2: Talazoparib (Ewing Cancer) | Part 2: Talazoparib (Pancreatic Cancer) | Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 2: Talazoparib (Breast Cancer) | Part 1: Talazoparib 1100 mcg/Day | Part 1: Talazoparib 1000 mcg/Day | Part 1: Talazoparib 900 mcg/Day | Part 1: Talazoparib 600 mcg/Day | Part 1: Talazoparib 400 mcg/Day | Part 1: Talazoparib 200 mcg/Day | Part 1: Talazoparib 100 mcg/Day | Part 1: Talazoparib 50 mcg/Day | Part 1: Talazoparib 25 mcg/Day |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.7 years STANDARD_DEVIATION 16.8 | 57.3 years STANDARD_DEVIATION 8.14 | 64.0 years STANDARD_DEVIATION 10.45 | 28.7 years STANDARD_DEVIATION 15.18 | 65.2 years STANDARD_DEVIATION 7.71 | 54.2 years STANDARD_DEVIATION 10.93 | 46.5 years STANDARD_DEVIATION 11.47 | 38.8 years STANDARD_DEVIATION 13.73 | 45.0 years STANDARD_DEVIATION 18.25 | 48.2 years STANDARD_DEVIATION 8.66 | 61.3 years STANDARD_DEVIATION 19 | 60.7 years STANDARD_DEVIATION 5.77 | 48.7 years STANDARD_DEVIATION 11.5 | 64.0 years STANDARD_DEVIATION 9.64 | 66.7 years STANDARD_DEVIATION 9.07 | 77.7 years STANDARD_DEVIATION 3.51 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 3 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 2 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Pacific Islander | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Other | 3 participants | 0 participants | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 101 participants | 3 participants | 23 participants | 10 participants | 10 participants | 11 participants | 9 participants | 4 participants | 5 participants | 5 participants | 6 participants | 3 participants | 3 participants | 3 participants | 3 participants | 3 participants |
| Sex: Female, Male Female | 76 Participants | 0 Participants | 11 Participants | 6 Participants | 4 Participants | 11 Participants | 11 Participants | 5 Participants | 5 Participants | 6 Participants | 5 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 34 Participants | 3 Participants | 12 Participants | 6 Participants | 6 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 3 / 3 | 2 / 3 | 3 / 3 | 3 / 3 | 6 / 6 | 6 / 6 | 6 / 6 | 6 / 6 | 12 / 12 | 11 / 11 | 10 / 10 | 12 / 12 | 20 / 23 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 2 / 3 | 3 / 3 | 0 / 3 | 2 / 6 | 3 / 6 | 2 / 6 | 3 / 6 | 2 / 12 | 5 / 11 | 6 / 10 | 4 / 12 | 8 / 23 | 0 / 3 |
Outcome results
Primary
Duration of Response
Duration of response was defined as the time (in weeks) from the date of the first documented objective response confirmed at least 28 days later to the date of the first documented PD or date of death, whichever occurred first. PD as per RECIST version 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time frame: Baseline until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
Population: Analysis performed on subset of response analysis population which included participants who had objective response. Data for outcome measure was planned to be analyzed combined for Part 1 and Part 2. Overall number of participants analyzed is zero (0) for arms of ewing, prostate, CLC cancer, since none of the participants had objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Duration of Response | 32.2 weeks |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Duration of Response | 26.9 weeks |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Duration of Response | NA weeks |
| Part 2: Talazoparib (SCLC Cancer) | Duration of Response | 13.6 weeks |
Primary
Number of Participants With Best Overall Response
Best overall response: best response (in the order of confirmed CR, confirmed PR, stable disease \[SD\] and progressive disease \[PD\]) among all overall response as RECIST 1.1, recorded from date of first dose of talazoparib until participant withdrew from study/data cut-off date, whichever earlier. CR defined as disappearance of all non-nodal target lesions (where all target lesions recorded with a length of 0 mm on the CRF) and the reduction of the shortest diameter of all nodal lesions to \< 10 mm. PR defined as at least a 30% decrease in sum of the diameters of target lesions, reference to baseline sum diameters. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time frame: From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
Population: Response analysis population: all enrolled participants who had at least 1 dose of talazoparib, and measurable disease at baseline. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for Part 1: Colorectal Cancer arm, as pre-specified in protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Number of Participants With Best Overall Response | Complete Response (CR) | 1 participants |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Number of Participants With Best Overall Response | Partial Response (PR) | 7 participants |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Number of Participants With Best Overall Response | Stable Disease (SD) | 7 participants |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Number of Participants With Best Overall Response | Progressive Disease (PD) | 5 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Number of Participants With Best Overall Response | Stable Disease (SD) | 10 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Number of Participants With Best Overall Response | Partial Response (PR) | 11 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Number of Participants With Best Overall Response | Complete Response (CR) | 1 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Number of Participants With Best Overall Response | Progressive Disease (PD) | 6 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Number of Participants With Best Overall Response | Progressive Disease (PD) | 6 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Number of Participants With Best Overall Response | Stable Disease (SD) | 2 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Number of Participants With Best Overall Response | Partial Response (PR) | 2 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Number of Participants With Best Overall Response | Complete Response (CR) | 0 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Number of Participants With Best Overall Response | Complete Response (CR) | 0 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Number of Participants With Best Overall Response | Progressive Disease (PD) | 9 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Number of Participants With Best Overall Response | Partial Response (PR) | 0 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Number of Participants With Best Overall Response | Stable Disease (SD) | 4 participants |
| Part 2: Talazoparib (SCLC Cancer) | Number of Participants With Best Overall Response | Stable Disease (SD) | 4 participants |
| Part 2: Talazoparib (SCLC Cancer) | Number of Participants With Best Overall Response | Progressive Disease (PD) | 14 participants |
| Part 2: Talazoparib (SCLC Cancer) | Number of Participants With Best Overall Response | Partial Response (PR) | 2 participants |
| Part 2: Talazoparib (SCLC Cancer) | Number of Participants With Best Overall Response | Complete Response (CR) | 0 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Number of Participants With Best Overall Response | Partial Response (PR) | 0 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Number of Participants With Best Overall Response | Stable Disease (SD) | 1 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Number of Participants With Best Overall Response | Progressive Disease (PD) | 0 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Number of Participants With Best Overall Response | Complete Response (CR) | 0 participants |
Primary
Number of Participants With Objective Response
Objective response in participants was defined as the number of participants with complete response (CR) or partial response (PR) after treatment with talazoparib and maintained for at least 4 weeks (28 days) as assessed by response evaluation criteria in solid tumors (RECIST) version 1.1. CR defined as disappearance of all non-nodal target lesions (where all target lesions were recorded with a length of 0 millimeter \[mm\] on the case report form \[CRF\]) and the reduction of the shortest diameter of all nodal lesions to less than \[\<\] 10 mm. PR was defined by a 30% or more decrease in the sum of the longest diameters (SLD) + sum of shortest diameters (SSD) of target lesions, taking as reference the baseline SLD+SSD.
Time frame: From Baseline until disease progression or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
Population: Response analysis population: all enrolled participants who had at least 1 dose of talazoparib, and measurable disease at baseline. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Number of Participants With Objective Response | 8 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Number of Participants With Objective Response | 12 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Number of Participants With Objective Response | 2 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Number of Participants With Objective Response | 0 participants |
| Part 2: Talazoparib (SCLC Cancer) | Number of Participants With Objective Response | 2 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Number of Participants With Objective Response | 0 participants |
| Part 1: Talazoparib (Colorectal Cancer) | Number of Participants With Objective Response | 0 participants |
Primary
Number of Participants With Stable Disease
SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD defined as at least a 20% increase in sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time frame: Baseline, until PD or death due to any cause (maximum duration: 1071 days for Part 1; 834 days for Part 2)
Population: Response analysis population: all enrolled participants who had at least 1 dose of talazoparib, and measurable disease at baseline. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for Part 1: Colorectal Cancer arm, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Number of Participants With Stable Disease | 7 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Number of Participants With Stable Disease | 10 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Number of Participants With Stable Disease | 2 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Number of Participants With Stable Disease | 4 participants |
| Part 2: Talazoparib (SCLC Cancer) | Number of Participants With Stable Disease | 4 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Number of Participants With Stable Disease | 1 participants |
Primary
Part 1: Maximum Tolerated Dose (MTD)
The MTD was defined as the highest dose at which no more than 1 of 6 participants experienced a Dose Limiting Toxicity (DLT). DLT defined as any of the following occurring during cycle 1 of part 1 of study, Hematologic toxicity: Any grade 4 or higher hematologic adverse event, Grade 3 thrombocytopenia associated with grade 2 or higher haemorrhage, Grade 3 thrombocytopenia or neutropenia that led to interruption of dosing for 5 or more days. Nonhematologic toxicity: grade 3 or higher laboratory AE which was asymptomatic and rapidly reversible adverse events (returned to baseline or to grade 1 or lower within 7 days), Grade 3 nausea, vomiting, or diarrhea that could be medically managed to grade 2 or lower with anti-emetics and/or anti-diarrheals within 24 hours, Grade 3 fatigue that improved to grade 2 or lower in 5 days or less, Alopecia. Grades based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03.
Time frame: Cycle 1 (Day 1 up to Day 42)
Population: Safety analysis set included all enrolled participants who received at least 1 dose of talazoparib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Maximum Tolerated Dose (MTD) | 1000 mcg/day |
Primary
Part 1: Recommended Part 2 Dose of Talazoparib
The Recommended dose of talazoparib for use in Part 2 was determined in Part 1 (dose escalation) on the basis of the totality of safety, pharmacokinetics (PK), pharmacodynamic and preliminary efficacy data observed in Cycles 1 and 2 and beyond.
Time frame: Baseline up to Cycle 50 (each cycle 28 days)
Population: Safety analysis set included all enrolled participants who received at least 1 dose of talazoparib.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Recommended Part 2 Dose of Talazoparib | 1000 mcg/day |
Primary
Progression-Free Survival (PFS)
PFS was defined as the time (in weeks) from the date of first dose of study drug to the earlier date of the documented PD or death due to any cause. PD as per RECIST 1.1 defined as at least a 20% increase in the sum of diameters of target lesions, reference to the smallest sum on study (this includes the baseline sum if that was the smallest on study).
Time frame: Baseline, until PD or death due to any cause (maximum duration:1071 days for Part 1; 834 days for Part 2)
Population: Full analysis set (FAS) included all enrolled participants who received at least 1 dose of talazoparib. Data for this outcome measure was planned to be analyzed combined for Part 1 and Part 2 on the basis of cancer type and was not planned to be analyzed for Part 1: Colorectal Cancer arm, as pre-specified in protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Progression-Free Survival (PFS) | 29.3 weeks |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Progression-Free Survival (PFS) | 32.1 weeks |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Progression-Free Survival (PFS) | 5.3 weeks |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Progression-Free Survival (PFS) | 6.2 weeks |
| Part 2: Talazoparib (SCLC Cancer) | Progression-Free Survival (PFS) | 11.1 weeks |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Progression-Free Survival (PFS) | 12.1 weeks |
Other Pre-specified
Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to end of study (up to 1071 days for Part 1 and up to 834 days for Part 2) that were absent before treatment or that worsened relative to pre-treatment state.
Time frame: Part 1: Baseline up to 1071 days; Part 2: Baseline up to 834 days
Population: Safety analyses set included all enrolled participants who received at least 1 dose of talazoparib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 2 participants |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 1 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 3 participants |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 2 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 2 participants |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 2 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 3 participants |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 3 participants |
| Part 2: Talazoparib (SCLC Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 0 participants |
| Part 2: Talazoparib (SCLC Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 3 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 2 participants |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 6 participants |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 6 participants |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 3 participants |
| Part 1: Talazoparib 1000 mcg/Day | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 6 participants |
| Part 1: Talazoparib 1000 mcg/Day | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 1 participants |
| Part 1: Talazoparib 1100 mcg/Day | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 6 participants |
| Part 1: Talazoparib 1100 mcg/Day | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 3 participants |
| Part 2: Talazoparib (Breast Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 2 participants |
| Part 2: Talazoparib (Breast Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 12 participants |
| Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 11 participants |
| Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 5 participants |
| Part 2: Talazoparib (Pancreatic Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 6 participants |
| Part 2: Talazoparib (Pancreatic Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 10 participants |
| Part 2: Talazoparib (Ewing Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 4 participants |
| Part 2: Talazoparib (Ewing Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 12 participants |
| Part 2: Talazoparib (SCLC Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 21 participants |
| Part 2: Talazoparib (SCLC Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 8 participants |
| Part 2: Talazoparib (Prostate Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | SAEs | 0 participants |
| Part 2: Talazoparib (Prostate Cancer) | Part 1 and 2: Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events | AEs | 2 participants |
Other Pre-specified
Part 1: Apparent Oral Clearance (CL/F) of Talazoparib
Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed.
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 5.17 liter/hour | Standard Deviation 2.1 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 6.27 liter/hour | Standard Deviation 1.66 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 2.72 liter/hour | Standard Deviation 0.532 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 2.61 liter/hour | Standard Deviation 1.35 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 6.95 liter/hour | Standard Deviation 1.71 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 5.19 liter/hour | Standard Deviation 0.99 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 5.49 liter/hour | Standard Deviation 2.08 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 5.39 liter/hour | Standard Deviation 1.59 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Apparent Oral Clearance (CL/F) of Talazoparib | 5.32 liter/hour | Standard Deviation 1.64 |
Other Pre-specified
Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib
Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vz/F was influenced by the fraction absorbed.
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 756 liter | Standard Deviation 351 |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 1070 liter | Standard Deviation 971 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 1240 liter | Standard Deviation 742 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 1020 liter | Standard Deviation 345 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 839 liter | Standard Deviation 487 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 475 liter | Standard Deviation 47.8 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 678 liter | Standard Deviation 217 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 264 liter | Standard Deviation 249 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 1050 liter | Standard Deviation 431 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 818 liter | Standard Deviation 326 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 477 liter | Standard Deviation 136 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 441 liter | Standard Deviation 143 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 604 liter | Standard Deviation 169 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 468 liter | Standard Deviation 169 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 415 liter | Standard Deviation 170 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 373 liter | Standard Deviation 144 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 1 | 549 liter | Standard Deviation 232 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Apparent Volume of Distribution (Vz/F) of Talazoparib | Cycle 1 Day 35 | 472 liter | Standard Deviation 254 |
Other Pre-specified
Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib
AUC (0-inf) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time.
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 5330 pg*hr/mL | Standard Deviation 1840 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 8320 pg*hr/mL | Standard Deviation 1960 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 37600 pg*hr/mL | Standard Deviation 6620 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 92700 pg*hr/mL | Standard Deviation 48500 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 60100 pg*hr/mL | Standard Deviation 15900 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 120000 pg*hr/mL | Standard Deviation 26000 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 188000 pg*hr/mL | Standard Deviation 85700 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 200000 pg*hr/mL | Standard Deviation 64000 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-inf)] of Talazoparib | 235000 pg*hr/mL | Standard Deviation 111000 |
Other Pre-specified
Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib
Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last).
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 3600 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 1360 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 5340 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 1960 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 16600 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 5320 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 39300 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 11700 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 43700 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 15000 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 97900 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 30000 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 160000 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 66100 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 182000 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 62400 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | 201000 picograms*hour per mililiter (pg*hr/mL) | Standard Deviation 93400 |
Other Pre-specified
Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
Population: The pharmacokinetic (PK) evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 60.0 picograms per milliliter (pg/mL) | Standard Deviation 15.9 |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 300 picograms per milliliter (pg/mL) | Standard Deviation 78.8 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 79.7 picograms per milliliter (pg/mL) | Standard Deviation 7.5 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 615 picograms per milliliter (pg/mL) | Standard Deviation 74.2 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 214 picograms per milliliter (pg/mL) | Standard Deviation 50.9 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 1880 picograms per milliliter (pg/mL) | Standard Deviation 332 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 788 picograms per milliliter (pg/mL) | Standard Deviation 369 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 5620 picograms per milliliter (pg/mL) | Standard Deviation 3530 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 1830 picograms per milliliter (pg/mL) | Standard Deviation 699 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 6560 picograms per milliliter (pg/mL) | Standard Deviation 1500 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 11300 picograms per milliliter (pg/mL) | Standard Deviation 3230 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 4100 picograms per milliliter (pg/mL) | Standard Deviation 1400 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 15400 picograms per milliliter (pg/mL) | Standard Deviation 1540 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 6100 picograms per milliliter (pg/mL) | Standard Deviation 3060 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 10600 picograms per milliliter (pg/mL) | Standard Deviation 4220 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 21000 picograms per milliliter (pg/mL) | Standard Deviation 7990 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 13200 picograms per milliliter (pg/mL) | Standard Deviation 3220 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 35 | 23400 picograms per milliliter (pg/mL) | Standard Deviation 4810 |
Other Pre-specified
Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 35
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 169 pg/mL | Standard Deviation 58 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 299 pg/mL | Standard Deviation 133 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 1020 pg/mL | Standard Deviation 107 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 2880 pg/mL | Standard Deviation 1710 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 2230 pg/mL | Standard Deviation 957 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 3470 pg/mL | Standard Deviation 1050 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 3180 pg/mL | Standard Deviation 802 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 3720 pg/mL | Standard Deviation 1590 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Minimum Observed Plasma Concentration (Cmin) of Talazoparib | 2910 pg/mL | Standard Deviation 803 |
Other Pre-specified
Part 1: Terminal Half-Life (t1/2) of Talazoparib
T1/2 is the time measured for the plasma concentration of talazoparib to decrease by one half.
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. Data for this outcome measure was not planned to be analyzed for Part 2, as pre-specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 107 Hours | Standard Deviation 84.2 |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 100 Hours | Standard Deviation 11.9 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 132 Hours | Standard Deviation 12.3 |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 129 Hours | Standard Deviation 42.6 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 229 Hours | Standard Deviation 158 |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 98.2 Hours | Standard Deviation 4.83 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 212 Hours | Standard Deviation 126 |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 50.9 Hours | Standard Deviation 19.1 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 102 Hours | Standard Deviation 27.2 |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 90.7 Hours | Standard Deviation 32.7 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 63.7 Hours | Standard Deviation 12.7 |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 58.6 Hours | Standard Deviation 17.3 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 60.4 Hours | Standard Deviation 10.9 |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 71.0 Hours | Standard Deviation 14.5 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 52.9 Hours | Standard Deviation 13.4 |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 50.0 Hours | Standard Deviation 16.6 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 35 | 52.8 Hours | Standard Deviation 23.2 |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Terminal Half-Life (t1/2) of Talazoparib | Cycle 1 Day 1 | 71.0 Hours | Standard Deviation 20.6 |
Other Pre-specified
Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
Time frame: Cycle 1: 0.25, 0.5, 0.75, 1, 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours postdose on Day 1 and Day 35
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 7.92 hours |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 1.02 hours |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 1.00 hours |
| Part 1 and Part 2: Talazoparib (Ovarian/ Peritoneal Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 5.43 hours |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 1.02 hours |
| Part 1 and Part 2: Talazoparib (Pancreatic Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 0.785 hours |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 1.03 hours |
| Part 1 and Part 2: Talazoparib (Ewing Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 1.97 hours |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 2.03 hours |
| Part 2: Talazoparib (SCLC Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 0.980 hours |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 1.04 hours |
| Part 1 and Part 2: Talazoparib (Prostate Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 0.835 hours |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 1.02 hours |
| Part 1: Talazoparib (Colorectal Cancer) | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 2.00 hours |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 1.03 hours |
| Part 1: Talazoparib 1000 mcg/Day | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 1.02 hours |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 1.00 hours |
| Part 1: Talazoparib 1100 mcg/Day | Part 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 35 | 1.48 hours |
Other Pre-specified
Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib
Area under the plasma concentration time-curve from zero to the time of last measured concentration (AUC0-last).
Time frame: Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall participants in Part 2, as pre-specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | Cycle 1 Day 1 | 19100 pg*hr/mL | Standard Deviation 8850 |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 2: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUC0-last) of Talazoparib | Cycle 2 Day 1 | 50200 pg*hr/mL | Standard Deviation 16300 |
Other Pre-specified
Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib
Time frame: Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall participants in Part 2, as pre-specified in protocol.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 1 Day 1 | 8480 pg/mL | Standard Deviation 3890 |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 2: Maximum Observed Plasma Concentration (Cmax) of Talazoparib | Cycle 2 Day 1 | 17700 pg/mL | Standard Deviation 5790 |
Other Pre-specified
Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib
Time frame: Cycle 1 and 2: Predose, 0.5, 1, 2, 3 and 4 hours postdose on Day 1
Population: The PK evaluable population included all participants who received at least 1 dose of talazoparib with adequate PK results to perform PK calculations and was used for analysis of PK endpoints. PK data was planned to be reported for the overall participants in Part 2, as pre-specified in protocol.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 1 Day 1 | 1.00 hours |
| Part 1 and Part 2: Talazoparib (Breast Cancer) | Part 2: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Talazoparib | Cycle 2 Day 1 | 1.07 hours |