Neoplasms
Conditions
Brief summary
A phase1 study to evaluate the PK (single dose and multiple doses) and safety of talazoparib 1 mg Once Daily in Chinese adult participants with advanced solid tumors. A maximum of approximately 15 participants will be enrolled such that approximately 12 evaluable participants complete the study.
Interventions
DRUGtalazoparib
Talazoparib will be administered orally on a continuous basis. Each cycle will consist of 28 days.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available. * ECOG Performance Status 0 or 1. * Adequate Bone Marrow, Renal and Liver Function.
Exclusion criteria
* Participants with brain metastases. * Current or anticipated use of P gp inhibitor and/or inducer within 7 days prior to study intervention from lead-in to end of Cycle 1; concomitant use of potent P gp inhibitor after Cycle 1 until the end of treatment. * Prior treatment with a PARP inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Maximum plasma concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Cmax was directly observed from data. |
| Time to Cmax (Tmax) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Time to reach Cmax (maximum plasma concentration) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. |
| Area Under Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Area under the plasma concentration versus time curve from time zero to the time tau (=24 hours) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. |
| Apparent Oral Clearance (CL/F) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Apparent oral clearance of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time. |
| Apparent Volume of Distribution (Vz/F) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Apparent volume of distribution of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCinf is area under the plasma concentration versus time curve from time zero extrapolated to infinite time. |
| Terminal Half-Life (t1/2) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Terminal half-life of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. t1/2 is defined as the time for plasma concentration of drug to decrease by one half. |
| Area Under Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) of Talazoparib Following Single Oral Dose | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing | Area under the plasma concentration versus time curve from time zero extrapolated to infinite time of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. |
| Cmax of Talazoparib Following Multiple Oral Doses (Steady State) | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22. | Maximum plasma concentration of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. |
| Tmax of Talazoparib Following Multiple Oral Doses (Steady State) | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22. | Time for Cmax of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. |
| Minimum Plasma Concentration (Cmin) of Talazoparib Following Multiple Oral Doses (Steady State) | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22. | Minimum plasma concentration observed during the dosing interval at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. |
| AUCtau of Talazoparib Following Multiple Oral Doses (Steady State) | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22. | Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. |
| CL/F of Talazoparib Following Multiple Oral Doses (Steady State) | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22. | Apparent clearance at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. Steady-state CL/F is calculated as dose/AUCtau. AUCtau = area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses. |
| Observed Accumulation Ratio (Rac) of Talazoparib Following Multiple Oral Doses (Steady State) | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22. | Observed accumulation ratio at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rac is calculated as AUCtau/AUCsd,tau, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCsd,tau = area under the plasma concentration versus time curve from time zero extrapolated to the time tau (=24 hours) after single dose. |
| Steady-State Accumulation Ratio (Rss) of Talazoparib Following Multiple Oral Doses (Steady State) | Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22. | Steady-state accumulation ratio after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rss is calculated as AUCtau/AUCinf, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCinf = Area under the plasma concentration versus time curve from time zero extrapolated to infinite time after single dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures | From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks) | Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. |
| Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks) | Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks) | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1(mild)=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-related TEAEs were determined by the investigator. |
| Duration of Response (DOR) for Participant(s) Achieving CR or PR | Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause (maximum of approximately 45 weeks) | Tumor assessments were performed regularly during Cycles 1-12 and per local standard practice after Cycle 12. Per RECIST v1.1, CR=complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Short diameter is used in the sum for target nodes, while longest diameter is used in the sum for all other target lesions. For participants with an OR (CR or PR), DOR = the time from first documentation of CR or PR to date of first documentation of objective progression or death. DOR data were censored on the date of last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. DOR was only calculated for participant(s) with an objective response. DOR was to be summarized using the Kaplan-Meier method if data permitted. |
| Percentage of Participants Achieving Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) (Confirmed or Unconfirmed) | Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause (maximum of approximately 45 weeks) | Tumor assessments were performed regularly during Cycles 1-12, then per local standard practice after Cycle 12. OR by investigator assessment was defined as a CR or PR according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause. CR is defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Short diameter is used in the sum for target nodes, while longest diameter is used in the sum for all other target lesions. An exact 95% confidence interval (CI) was calculated using Clopper-Pearson method. Given the exploratory nature of this endpoint, confirmation of response (CR/PR) was not required per protocol. |
| Number of Participants With Serious Adverse Events (SAEs) | Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks) | An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator. |
| Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated. Treatment-related TEAEs were determined by the investigator. Grade 3 or 4 TEAEs reported by at least 1 participant are reported here. |
| Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated. Treatment-related TEAEs were determined by the investigator. Grade 3 or 4 treatment-related TEAEs reported by at least 1 participant are reported here. |
| Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Treatment-related TEAEs were determined by the investigator. |
| Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Treatment-related TEAEs were determined by the investigator. |
| Number of Participants With TEAEs Leading to Discontinuation From Talazoparib by PT | Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Treatment-related TEAEs were determined by the investigator. |
| Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks) | Hematology lab parameters included hemoglobin, hematocrit, red blood cell (RBC) count, platelet count, white blood cell (WBC) count, neutrophils%, eosinophils%, monocytes%, basophils%, lymphocytes%. Grades of lab abnormalities were defined per NCI CTCAE version 4.03. Grade 1(mild)=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated. On-treatment is defined as time from first dose date of talazoparib through at least 28 days after last dose or start day of new anti-cancer therapy minus 1 day. Shifts meeting criteria and reported in at least 1 participant are reported in this OM. |
| Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks) | Chemistry lab parameters included blood urea nitrogen or urea,creatinine,glucose (fasting),calcium,sodium,potassium,magnesium,chloride,aspartate aminotransferase,alanine aminotransferase,total bilirubin,alkaline phosphatase,uric acid,albumin,total protein,creatinine clearance. Grades of lab results were defined per NCI CTCAE v4.03.Grade 1=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated.On-treatment=time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. Shifts meeting criteria and reported in at least 1 participant are reported. |
| Number of Participants With On-Treatment Urinalysis Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks) | Urinalysis examined pH,glucose,protein,blood,ketones,nitrites,leukocyte esterase/leukocytes,urobilinogen,urine bilirubin,microscopy. Grades of lab results were defined by NCI CTCAE v4.03. Grade 1(mild)=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated. On-treatment=time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. This OM is based only on lab data. Grade 4 proteinuria cannot be assessed based only on lab data, so is not applicable/not reported. |
| Number of Participants With On-Treatment Vital Signs Data Meeting Pre-Specified Criteria for Potentially Clinically Significant Results | From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks) | Vital signs data included systolic and diastolic blood pressure (BP), pulse rate, respiratory rate (RR), temperature and weight. BP and pulse rate were recorded in sitting position. Potentially clinically significant vital signs abnormalities are defined as: systolic BP absolute result \>180 mmHg and increase from baseline ≥40 mmHg, absolute result \<90 mmHg and decrease from baseline \>30 mmHg; diastolic BP absolute result \>110 mmHg and increase from baseline ≥30 mmHg, absolute result \<50 mmHg and decrease from baseline \>20 mmHg, increase from baseline ≥20 mmHg; pulse rate absolute result \>120 beats per minute (bpm) and increase from baseline \>30 bpm, absolute result \<50 bpm and decrease from baseline \> 20 bpm; weight \>10% decrease from baseline. Participants with vital signs data meeting any criteria above are reported in this OM if any. On-treatment is defined as time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. |
| Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks) | Standard 12-lead electrocardiograms (ECGs) utilizing limb leads (with a 10 second rhythm strip) were collected using an ECG machine that automatically calculated the heart rate and measured PR, RR, QT intervals, QTc, QTcF and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. |
| Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category | From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks) | Standard 12-lead electrocardiograms (ECGs) utilizing limb leads (with a 10 second rhythm strip) were collected using an ECG machine that automatically calculated the heart rate and measured PR, RR, QT intervals, QTc, QTcF and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. |
| Number of Participants With On-Treatment Concomitant Medications | From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks) | Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. |
| Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT | From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks) | Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. On-treatment concomitant medications reported in at least 20% participants are reported for this OM. |
Countries
China
Participant flow
Pre-assignment details
A total of 15 participants were enrolled and received talazoparib 1 mg once daily (QD).
Participants by arm
| Arm | Count |
|---|---|
| Talazoparib 1 mg QD Participants received a single oral dose of talazoparib 1mg on Day -9 (lead-in dose), and then received talazoparib 1mg QD in 28-day cycles (maximum 9 cycles), starting from Cycle 1 Day 1. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Progressive disease | 13 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Talazoparib 1 mg QD |
|---|---|
| Age, Continuous | 53 years |
| Age, Customized 18 to <45 years | 4 Participants |
| Age, Customized 45 to <65 years | 8 Participants |
| Age, Customized >=65 years | 3 Participants |
| Race/Ethnicity, Customized Asian | 15 Participants |
| Race/Ethnicity, Customized Chinese | 15 Participants |
| Race/Ethnicity, Customized Other (Not Chinese) | 0 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 3 / 15 |
Outcome results
Primary
Apparent Oral Clearance (CL/F) of Talazoparib Following Single Oral Dose
Apparent oral clearance of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this outcome measure (OM).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Apparent Oral Clearance (CL/F) of Talazoparib Following Single Oral Dose | 4.798 liter/hour (L/hr) | Geometric Coefficient of Variation 31 |
Primary
Apparent Volume of Distribution (Vz/F) of Talazoparib Following Single Oral Dose
Apparent volume of distribution of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCinf is area under the plasma concentration versus time curve from time zero extrapolated to infinite time.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Apparent Volume of Distribution (Vz/F) of Talazoparib Following Single Oral Dose | 456.8 Liter | Geometric Coefficient of Variation 37 |
Primary
Area Under Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) of Talazoparib Following Single Oral Dose
Area under the plasma concentration versus time curve from time zero extrapolated to infinite time of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Area Under Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) of Talazoparib Following Single Oral Dose | 208.3 ng*hr/mL | Geometric Coefficient of Variation 31 |
Primary
Area Under Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Talazoparib Following Single Oral Dose
Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of interest in the single-dose and/or multiple dose PK part.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Area Under Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Talazoparib Following Single Oral Dose | 172.0 ng*hr/mL | Geometric Coefficient of Variation 32 |
Primary
Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of Talazoparib Following Single Oral Dose
Area under the plasma concentration versus time curve from time zero to the time tau (=24 hours) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of interest in the single-dose and/or multiple dose PK part.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of Talazoparib Following Single Oral Dose | 86.54 ng*hr/mL | Geometric Coefficient of Variation 29 |
Primary
AUCtau of Talazoparib Following Multiple Oral Doses (Steady State)
Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | AUCtau of Talazoparib Following Multiple Oral Doses (Steady State) | 147.8 ng*hr/mL | Geometric Coefficient of Variation 123 |
Primary
CL/F of Talazoparib Following Multiple Oral Doses (Steady State)
Apparent clearance at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. Steady-state CL/F is calculated as dose/AUCtau. AUCtau = area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | CL/F of Talazoparib Following Multiple Oral Doses (Steady State) | 6.770 L/hr | Geometric Coefficient of Variation 123 |
Primary
Cmax of Talazoparib Following Multiple Oral Doses (Steady State)
Maximum plasma concentration of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed data to this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Cmax of Talazoparib Following Multiple Oral Doses (Steady State) | 14.35 ng/mL | Geometric Coefficient of Variation 169 |
Primary
Maximum Observed Concentration (Cmax) of Talazoparib Following Single Oral Dose
Maximum plasma concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Cmax was directly observed from data.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the pharmacokinetic (PK) parameters of interest in the single-dose and/or multiple dose PK part.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Maximum Observed Concentration (Cmax) of Talazoparib Following Single Oral Dose | 8.506 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
Primary
Minimum Plasma Concentration (Cmin) of Talazoparib Following Multiple Oral Doses (Steady State)
Minimum plasma concentration observed during the dosing interval at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed data to this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Minimum Plasma Concentration (Cmin) of Talazoparib Following Multiple Oral Doses (Steady State) | 2.616 ng/mL | Geometric Coefficient of Variation 95 |
Primary
Observed Accumulation Ratio (Rac) of Talazoparib Following Multiple Oral Doses (Steady State)
Observed accumulation ratio at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rac is calculated as AUCtau/AUCsd,tau, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCsd,tau = area under the plasma concentration versus time curve from time zero extrapolated to the time tau (=24 hours) after single dose.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Observed Accumulation Ratio (Rac) of Talazoparib Following Multiple Oral Doses (Steady State) | 1.733 ratio | Geometric Coefficient of Variation 127 |
Primary
Steady-State Accumulation Ratio (Rss) of Talazoparib Following Multiple Oral Doses (Steady State)
Steady-state accumulation ratio after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rss is calculated as AUCtau/AUCinf, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCinf = Area under the plasma concentration versus time curve from time zero extrapolated to infinite time after single dose.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Steady-State Accumulation Ratio (Rss) of Talazoparib Following Multiple Oral Doses (Steady State) | 0.6958 ratio | Geometric Coefficient of Variation 192 |
Primary
Terminal Half-Life (t1/2) of Talazoparib Following Single Oral Dose
Terminal half-life of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. t1/2 is defined as the time for plasma concentration of drug to decrease by one half.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed to the summary statistics of this OM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Terminal Half-Life (t1/2) of Talazoparib Following Single Oral Dose | 67.00 hours | Standard Deviation 11.779 |
Primary
Time to Cmax (Tmax) of Talazoparib Following Single Oral Dose
Time to reach Cmax (maximum plasma concentration) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of interest in the single-dose and/or multiple dose PK part.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Time to Cmax (Tmax) of Talazoparib Following Single Oral Dose | 1.90 hours |
Primary
Tmax of Talazoparib Following Multiple Oral Doses (Steady State)
Time for Cmax of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.
Time frame: Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.
Population: The analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in the single-dose and/or multiple dose PK part. Number of participants analyzed = number of participants in the analysis population that contributed data to this OM.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Tmax of Talazoparib Following Multiple Oral Doses (Steady State) | 1.85 hours |
Secondary
Duration of Response (DOR) for Participant(s) Achieving CR or PR
Tumor assessments were performed regularly during Cycles 1-12 and per local standard practice after Cycle 12. Per RECIST v1.1, CR=complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Short diameter is used in the sum for target nodes, while longest diameter is used in the sum for all other target lesions. For participants with an OR (CR or PR), DOR = the time from first documentation of CR or PR to date of first documentation of objective progression or death. DOR data were censored on the date of last tumor assessment on study for participants who did not have objective tumor progression and who did not die due to any cause while on study. DOR was only calculated for participant(s) with an objective response. DOR was to be summarized using the Kaplan-Meier method if data permitted.
Time frame: Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause (maximum of approximately 45 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention and had an objective response (CR or PR). Number of participants analyzed = number of participant(s) evaluable for this OM.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Duration of Response (DOR) for Participant(s) Achieving CR or PR | 172 Days |
Secondary
Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated. Treatment-related TEAEs were determined by the investigator. Grade 3 or 4 TEAEs reported by at least 1 participant are reported here.
Time frame: Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Abdominal distension | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Blood bilirubin increased | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Hypercholesterolaemia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Hyperglycaemia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 4 Hypernatraemia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 4 Hyperuricaemia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Hypokalaemia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Hyponatraemia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Neutropenia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Gamma-glutamyltransferase increased | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 4 Gamma-glutamyltransferase increased | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Neutrophil count decreased | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 4 Neutrophil count decreased | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Platelet count decreased | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 4 Platelet count decreased | 2 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Anaemia | 4 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade | Grade 3 Aspartate aminotransferase increased | 2 Participants |
Secondary
Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Grades of AEs were defined by NCI CTCAE version 4.03. Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated. Treatment-related TEAEs were determined by the investigator. Grade 3 or 4 treatment-related TEAEs reported by at least 1 participant are reported here.
Time frame: Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Grade 3 Anaemia | 4 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Grade 3 Neutrophil count decreased | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Grade 4 Neutrophil count decreased | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Grade 3 Platelet count decreased | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Grade 4 Platelet count decreased | 2 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Grade 3 Hyponatraemia | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade | Grade 3 Neutropenia | 1 Participants |
Secondary
Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade
Chemistry lab parameters included blood urea nitrogen or urea,creatinine,glucose (fasting),calcium,sodium,potassium,magnesium,chloride,aspartate aminotransferase,alanine aminotransferase,total bilirubin,alkaline phosphatase,uric acid,albumin,total protein,creatinine clearance. Grades of lab results were defined per NCI CTCAE v4.03.Grade 1=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated.On-treatment=time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. Shifts meeting criteria and reported in at least 1 participant are reported.
Time frame: From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Alkaline phosphatase increased: Grade 0 to Grade 3 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Aspartate aminotransferase: Grade 1 to Grade 3 | 2 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Blood bilirubin increased: Grade 0 to Grade 3 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Hyperglycemia: Grade 1 to Grade 3 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Hypernatremia: Grade 0 to Grade 4 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Hypokalemia: Grade 0 to Grade 3 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Chemistry Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Hyponatremia: Grade 0 to Grade 3 | 1 Participants |
Secondary
Number of Participants With On-Treatment Concomitant Medications
Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day.
Time frame: From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Medications | 14 Participants |
Secondary
Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT
Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. On-treatment concomitant medications reported in at least 20% participants are reported for this OM.
Time frame: From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT | Recombinant human thrombopoietin | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT | Lidocaine | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT | Glucose | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT | Dexamethasone sodium phosphate | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT | Granulocyte colony stimulating factor | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Medications With Frequency >=20% by PT | Herbal preparation | 3 Participants |
Secondary
Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures
Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day.
Time frame: From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures | 5 Participants |
Secondary
Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT
Concomitant medications or nondrug treatments/procedures were defined as medications or nondrug treatments/procedures, other than study intervention, which started prior to first dose date of study treatment and continued on on-treatment period as well as those started during the on-treatment period. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day.
Time frame: From first dose date up to at least 28 days after last dose/start day of new anti-cancer drug therapy minus 1 day (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Abdominal cavity drainage | 2 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Bladder catheterisation | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Endotracheal intubation | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Enema administration | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Enteral nutrition | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Oxygen therapy | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Platelet transfusion | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Therapeutic procedure | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Concomitant Nondrug Treatments/Procedures by PT | Transfusion | 3 Participants |
Secondary
Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade
Hematology lab parameters included hemoglobin, hematocrit, red blood cell (RBC) count, platelet count, white blood cell (WBC) count, neutrophils%, eosinophils%, monocytes%, basophils%, lymphocytes%. Grades of lab abnormalities were defined per NCI CTCAE version 4.03. Grade 1(mild)=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated. On-treatment is defined as time from first dose date of talazoparib through at least 28 days after last dose or start day of new anti-cancer therapy minus 1 day. Shifts meeting criteria and reported in at least 1 participant are reported in this OM.
Time frame: From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Anemia: Grade 0 to Grade 3 | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Anemia: Grade 1 to Grade 3 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Lymphocyte count decreased: Grade 0 to Grade 3 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Neutrophil count decreased: Grade 0 to Grade 3 | 5 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Neutrophil count decreased: Grade 0 to Grade 4 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Platelet count decreased: Grade 0 to Grade 3 | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Platelet count decreased: Grade 0 to Grade 4 | 2 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Hematology Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | White blood cell decreased: Grade 0 to Grade 3 | 1 Participants |
Secondary
Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category
Standard 12-lead electrocardiograms (ECGs) utilizing limb leads (with a 10 second rhythm strip) were collected using an ECG machine that automatically calculated the heart rate and measured PR, RR, QT intervals, QTc, QTcF and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day.
Time frame: From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category | QTcB interval increase from baseline <=30 msec | 9 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category | QTcB interval increase from baseline >30 msec and <=60 msec | 2 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category | QTcB interval increase from baseline >60 msec | 4 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category | QTcF interval increase from baseline <=30 msec | 9 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category | QTcF interval increase from baseline >30 msec and <=60 msec | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum Increase From Baseline in QTcB and QTcF Data by Category | QTcF interval increase from baseline >60 msec | 3 Participants |
Secondary
Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category
Standard 12-lead electrocardiograms (ECGs) utilizing limb leads (with a 10 second rhythm strip) were collected using an ECG machine that automatically calculated the heart rate and measured PR, RR, QT intervals, QTc, QTcF and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes. On-treatment is defined as the time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day.
Time frame: From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcB interval value <=450 millisecond (msec) | 9 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcB interval value >450 msec and <=480 msec | 5 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcB interval value >480 msec and <=500 msec | 0 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcB interval value >500 msec | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcF interval value <=450 msec | 14 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcF interval value >450 msec and <=480 msec | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcF interval value >480 msec and <=500 msec | 0 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Maximum QT Interval (Bazett's Correction) (QTcB) and QT Interval (Fridericia's Correction) (QTcF) Data by Category | QTcF interval value>500 msec | 0 Participants |
Secondary
Number of Participants With On-Treatment Urinalysis Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade
Urinalysis examined pH,glucose,protein,blood,ketones,nitrites,leukocyte esterase/leukocytes,urobilinogen,urine bilirubin,microscopy. Grades of lab results were defined by NCI CTCAE v4.03. Grade 1(mild)=asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated;Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL;Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; disabling limiting self-care ADL;Grade 4=life-threatening consequences, urgent intervention indicated. On-treatment=time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day. This OM is based only on lab data. Grade 4 proteinuria cannot be assessed based only on lab data, so is not applicable/not reported.
Time frame: From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention. Number of participants analyzed = number of participant evaluable for this OM.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Urinalysis Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Protenuria: Grade 0 to Grade 3 | 0 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Urinalysis Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Protenuria: Grade 1 to Grade 3 | 0 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Urinalysis Laboratory Abnormalities Shifting From <=Grade 2 at Baseline to Grade 3/4 Post-Baseline by Maximum CTCAE Grade | Protenuria: Grade 2 to Grade 3 | 0 Participants |
Secondary
Number of Participants With On-Treatment Vital Signs Data Meeting Pre-Specified Criteria for Potentially Clinically Significant Results
Vital signs data included systolic and diastolic blood pressure (BP), pulse rate, respiratory rate (RR), temperature and weight. BP and pulse rate were recorded in sitting position. Potentially clinically significant vital signs abnormalities are defined as: systolic BP absolute result \>180 mmHg and increase from baseline ≥40 mmHg, absolute result \<90 mmHg and decrease from baseline \>30 mmHg; diastolic BP absolute result \>110 mmHg and increase from baseline ≥30 mmHg, absolute result \<50 mmHg and decrease from baseline \>20 mmHg, increase from baseline ≥20 mmHg; pulse rate absolute result \>120 beats per minute (bpm) and increase from baseline \>30 bpm, absolute result \<50 bpm and decrease from baseline \> 20 bpm; weight \>10% decrease from baseline. Participants with vital signs data meeting any criteria above are reported in this OM if any. On-treatment is defined as time from first dose date through at least 28 days after last dose/start day of new anti-cancer therapy minus 1 day.
Time frame: From first dose date up to at least 28 days after last dose or to the start of new anti-cancer drug therapy minus 1 day (whichever was earlier) (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With On-Treatment Vital Signs Data Meeting Pre-Specified Criteria for Potentially Clinically Significant Results | 1 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs)
An SAE was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect. Treatment-related SAEs were determined by the investigator.
Time frame: Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Serious Adverse Events (SAEs) | All-causality SAE | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Serious Adverse Events (SAEs) | Treatment-related SAE | 3 Participants |
Secondary
Number of Participants With TEAEs Leading to Discontinuation From Talazoparib by PT
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Treatment-related TEAEs were determined by the investigator.
Time frame: Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Discontinuation From Talazoparib by PT | All-causality Neutrophil count decreased leading to discontinuation from talazoparib | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Discontinuation From Talazoparib by PT | Treatment-related Neutrophil count decreased leading to discontinuation from talazoparib | 1 Participants |
Secondary
Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Treatment-related TEAEs were determined by the investigator.
Time frame: Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | All-causality Anaemia leading to dose interruption | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | Treatment-related Anaemia leading to dose interruption | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | All-causality Aspartate aminotransferase increased leading to dose interruption | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | All-causality Neutrophil count decreased leading to dose interruption | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | Treatment-related Neutrophil count decreased leading to dose interruption | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | All-causality Platelet count decreased leading to dose interruption | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT | Treatment-related Platelet count decreased leading to dose interruption | 1 Participants |
Secondary
Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Treatment-related TEAEs were determined by the investigator.
Time frame: Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | All-causality Anaemia leading to dose reduction | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | Treatment-related Anaemia leading to dose reduction | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | All-causality Neutrophil count decreased leading to dose reduction | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | Treatment-related Neutrophil count decreased leading to dose reduction | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | All-causality Platelet count decreased leading to dose reduction | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | Treatment-related Platelet count decreased leading to dose reduction | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | All-causality Neutropenia leading to dose reduction | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | Treatment-related Neutropenia leading to dose reduction | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | All-causality Hypernatraemia leading to dose reduction | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | All-causality Hyponatraemia leading to dose reduction | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With TEAEs Leading to Dose Reduction of Talazoparib by PT | Treatment-related Hyponatraemia leading to dose reduction | 1 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with study treatment. TEAEs=AEs with start date during the on-treatment period (including on the date of first dose). Grades of AEs were defined by National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1(mild)=asymptomatic/mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2(moderate)=minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activity of daily living (ADL); Grade 3=severe or medically significant but not immediately life-threatening, hospitalization of prolongation of hospitalization indicated; disabling limiting self-care ADL; Grade 4=events with life-threatening consequences, urgent intervention indicated; Grade 5= death related to AE. Treatment-related TEAEs were determined by the investigator.
Time frame: Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality TEAEs | 14 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs | 13 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 all-causality TEAEs | 10 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 3 or 4 treatment-related TEAEs | 6 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Grade 5 TEAEs (TEAEs leading to death) | 0 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality TEAEs leading to dose interruption of talazoparib | 3 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs leading to dose interruption of talazoparib | 2 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality TEAEs leading to dose reduction of talazoparib | 5 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs leading to dose reduction of talazoparib | 5 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality TEAEs leading to discontinuation from talazoparib | 1 Participants |
| Talazoparib 1 mg Once Daily (QD) | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-related TEAEs leading to discontinuation from talazoparib | 1 Participants |
Secondary
Percentage of Participants Achieving Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) (Confirmed or Unconfirmed)
Tumor assessments were performed regularly during Cycles 1-12, then per local standard practice after Cycle 12. OR by investigator assessment was defined as a CR or PR according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 recorded from Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause. CR is defined as complete disappearance of all target lesions with the exception of nodal disease. All target nodes must decrease to normal size (short axis \<10 mm). PR is defined as \>=30% decrease under baseline of the sum of diameters of all target measurable lesions. Short diameter is used in the sum for target nodes, while longest diameter is used in the sum for all other target lesions. An exact 95% confidence interval (CI) was calculated using Clopper-Pearson method. Given the exploratory nature of this endpoint, confirmation of response (CR/PR) was not required per protocol.
Time frame: Cycle 1 Day 1 until disease progression, start of subsequent anti-cancer therapy or death due to any cause (maximum of approximately 45 weeks)
Population: The analysis population included all enrolled participants who received at least 1 dose of study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Talazoparib 1 mg Once Daily (QD) | Percentage of Participants Achieving Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) (Confirmed or Unconfirmed) | 6.7 Percentage of participants |