Cancer
Conditions
Brief summary
This is a single-arm, open-label, extended treatment, safety study in patients treated with talazoparib in qualifying studies.
Interventions
DRUGTalazoparib
Maximum starting dose: 1mg/day or last tolerated dose in the originating protocol
Sponsors
Medivation, Inc.
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
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. * Female patients of childbearing potential must have a negative pregnancy test before the first dose of talazoparib and must agree to use a highly effective birth control method from the time of the first dose of talazoparib through 45 days after the last dose. * Male patients must use a condom when having sex with a pregnant woman or with a woman of childbearing potential from the time of the first dose of talazoparib through 105 days after the last dose. Contraception should be considered for a nonpregnant female partner of childbearing potential. * Female patients may not be breastfeeding at the first dose of talazoparib and must not breastfeed during study participation through 45 days after the last dose of talazoparib.
Exclusion criteria
* Permanently discontinued from any Medivation sponsored study with talazoparib alone or in combination with another agent. * Received an antineoplastic therapy or investigational agent after treatment with talazoparib in the originating protocol. * Has a clinically significant cardiovascular, dermatologic, endocrine, gastrointestinal, hematologic, infectious, metabolic, neurologic, psychologic, or pulmonary disorder or any other condition, including excessive alcohol or drug abuse, or secondary malignancy, that may interfere with study participation in the opinion of the investigator. * Diagnosis of myelodysplastic syndrome (MDS).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death; inpatient hospitalization or prolongation of existing hospitalization; was life-threatening (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or was considered as an important medical event. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. AE included both SAEs and all non-SAEs. Treatment-related TEAEs were defined as any TEAE with at least a possible relationship to the study drug as assessed by the investigator or that was missing the assessment of causal relationship whose relationship to the study drug could not be ruled out. |
| Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4 | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Severity was graded using NCI-CTCAE version 4 where, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs were reported. |
| Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Number of participants with TEAEs leading to dose reduction, permanent study drug discontinuation and death were reported. |
| Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | The following liver parameters were analyzed: aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TBL) and alkaline phosphatase (ALP). The criteria for clinically significant abnormalities for liver parameters included AST or ALT greater than or equal to (\>=) 3 times upper limit of normal (ULN); ALT or AST greater than (\>) 5 times ULN; ALT or AST \> 10 times ULN; ALT or AST \> 20 times ULN; total TBL \>2 times ULN; ALT or AST \>= 3 times ULN and TBL \> 2 times ULN and ALT or AST \>= 3 times ULN and TBL \> 2 times ULN and ALP \< 2 times ULN. |
| Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | The following hematology parameters were analyzed: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 and 4 toxicities were reported. Low indicates values lower than the normal range. |
| Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | The following chemistry parameters were analyzed: alkaline phosphatase, bilirubin and creatinine. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 or 4 toxicities were reported. High indicates values higher than the normal range. |
| Number of Participants With Clinically Significant Changes in Vital Signs and Weight | From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years) | Criteria for clinically significant changes in vital signs included a) Systolic blood pressure (SBP): 1) absolute results \>180 millimeter of mercury (mmHg) and increase from baseline \>=40 mmHg, 2) absolute results \<90 mmHg and decrease from baseline \>30 mmHg; b) Diastolic blood pressure (DBP): 1) absolute results \>110 mmHg and increase from baseline \>=30 mmHg , 2) absolute results \<50 mmHg and decrease from baseline \>20 mmHg , 3) increase from baseline \>=20 mmHg; c) Heart rate: 1) absolute results \>120 beats per minute (bpm) and increase from baseline \>30 bpm, 2) absolute results \<50 bpm and \>20 bpm decrease from baseline; d) Temperature: \<=34.5 or \>=38 degree Celsius. Criteria for clinically significant changes in weight: \>10 percent (%) decrease from baseline. |
Countries
Canada, France, Germany, Hungary, Moldova, Poland, Russia, United Kingdom, United States
Participant flow
Recruitment details
Eligible participants who received talazoparib as a single agent or in combination with another agent in following qualifying studies: PRP-001(NCT01286987), MDV3800-01(NCT02997163), MDV3800-02(NCT02997176), MDV3800-03(NCT03070548), MDV3800-04(NCT03077607), MDV3800-14(NCT03042910) continued therapy with talazoparib as single agent in this extended treatment study.
Pre-assignment details
A total of 120 participants were enrolled in the study of which 118 participants received the study treatment and 2 participants did not receive any study treatment as they were withdrawn before treatment initiation. Hence those 2 participants were not reported under any reporting arms.
Participants by arm
| Arm | Count |
|---|---|
| Initial Dose Talazoparib: < 1 mg/Day Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of \< 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. | 66 |
| Initial Dose Talazoparib: 1 mg/Day Participants were administered talazoparib capsules at an initial dose (i.e. the last tolerated dose in the originating study) of 1 mg orally once daily. Participants received talazoparib till the investigator considered treatment to be providing clinical benefit or until other study discontinuation criteria were met. Participants were followed-up for safety until 30 days after the last dose of talazoparib (i.e., permanent discontinuation) or before initiation of a new antineoplastic therapy, whichever occurred first. | 52 |
| Total | 118 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 6 | 4 |
| Overall Study | Disease Progression | 47 | 38 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Other | 5 | 6 |
| Overall Study | Physician Decision | 3 | 2 |
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Initial Dose Talazoparib: < 1 mg/Day | Initial Dose Talazoparib: 1 mg/Day | Total |
|---|---|---|---|
| Age, Customized 50 to <65 years | 30 Participants | 17 Participants | 47 Participants |
| Age, Customized < 50 years | 10 Participants | 9 Participants | 19 Participants |
| Age, Customized >= 65 years | 25 Participants | 25 Participants | 50 Participants |
| Age, Customized Missing | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 56 Participants | 45 Participants | 101 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) White | 59 Participants | 48 Participants | 107 Participants |
| Sex: Female, Male Female | 46 Participants | 37 Participants | 83 Participants |
| Sex: Female, Male Male | 20 Participants | 15 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 66 | 8 / 52 |
| other Total, other adverse events | 54 / 66 | 46 / 52 |
| serious Total, serious adverse events | 27 / 66 | 18 / 52 |
Outcome results
Primary
Number of Participants With Clinically Significant Changes in Vital Signs and Weight
Criteria for clinically significant changes in vital signs included a) Systolic blood pressure (SBP): 1) absolute results \>180 millimeter of mercury (mmHg) and increase from baseline \>=40 mmHg, 2) absolute results \<90 mmHg and decrease from baseline \>30 mmHg; b) Diastolic blood pressure (DBP): 1) absolute results \>110 mmHg and increase from baseline \>=30 mmHg , 2) absolute results \<50 mmHg and decrease from baseline \>20 mmHg , 3) increase from baseline \>=20 mmHg; c) Heart rate: 1) absolute results \>120 beats per minute (bpm) and increase from baseline \>30 bpm, 2) absolute results \<50 bpm and \>20 bpm decrease from baseline; d) Temperature: \<=34.5 or \>=38 degree Celsius. Criteria for clinically significant changes in weight: \>10 percent (%) decrease from baseline.
Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
Population: Safety population included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | SBP: absolute results <90 mmHg and decrease from baseline >30 mmHg | 1 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Heart rate: absolute results >120 bpm and increase from baseline >30 bpm | 2 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | DBP: absolute results <50 mmHg and decrease from baseline >20 mmHg | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Heart rate: absolute results <50 bpm and decrease from baseline >20 bpm | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | DBP: absolute results >110 mmHg and increase from baseline >=30 mmHg | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Temperature: <=34.5 or >=38 degree Celsius | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | DBP: increase from baseline >=20 mmHg | 6 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Weight: >10% decrease from baseline | 7 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | SBP: absolute results >180 mmHg and increase from baseline >=40 mmHg | 1 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Weight: >10% decrease from baseline | 2 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | SBP: absolute results >180 mmHg and increase from baseline >=40 mmHg | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | SBP: absolute results <90 mmHg and decrease from baseline >30 mmHg | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | DBP: absolute results >110 mmHg and increase from baseline >=30 mmHg | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | DBP: absolute results <50 mmHg and decrease from baseline >20 mmHg | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | DBP: increase from baseline >=20 mmHg | 5 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Heart rate: absolute results >120 bpm and increase from baseline >30 bpm | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Heart rate: absolute results <50 bpm and decrease from baseline >20 bpm | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Changes in Vital Signs and Weight | Temperature: <=34.5 or >=38 degree Celsius | 0 Participants |
Primary
Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests
The following liver parameters were analyzed: aspartate transaminase (AST), alanine aminotransferase (ALT), total bilirubin (TBL) and alkaline phosphatase (ALP). The criteria for clinically significant abnormalities for liver parameters included AST or ALT greater than or equal to (\>=) 3 times upper limit of normal (ULN); ALT or AST greater than (\>) 5 times ULN; ALT or AST \> 10 times ULN; ALT or AST \> 20 times ULN; total TBL \>2 times ULN; ALT or AST \>= 3 times ULN and TBL \> 2 times ULN and ALT or AST \>= 3 times ULN and TBL \> 2 times ULN and ALP \< 2 times ULN.
Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
Population: Safety population included all participants who received any amount of talazoparib. Here, overall number of participants analyzed signifies number of participants who were evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST > 10*ULN | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | TBL > 2*ULN | 4 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST > 5*ULN | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST >= 3*ULN and TBL > 2*ULN (any visit date) | 2 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST > 20*ULN | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST >= 3*ULN and TBL > 2*ULN and ALP < 2*ULN (any visit date) | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST >= 3*ULN | 5 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST >= 3*ULN and TBL > 2*ULN and ALP < 2*ULN (any visit date) | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST >= 3*ULN | 2 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST > 5*ULN | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST > 10*ULN | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST > 20*ULN | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | TBL > 2*ULN | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Clinically Significant Laboratory Abnormalities: Liver Function Tests | ALT or AST >= 3*ULN and TBL > 2*ULN (any visit date) | 0 Participants |
Primary
Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4
An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Severity was graded using NCI-CTCAE version 4 where, Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. Number of participants with Grade 3 or 4 TEAEs were reported.
Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
Population: Safety population included all participants who received any amount of talazoparib.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4 | 38 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Grade 3 or 4 TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4 | 32 Participants |
Primary
Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters
The following chemistry parameters were analyzed: alkaline phosphatase, bilirubin and creatinine. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 or 4 toxicities were reported. High indicates values higher than the normal range.
Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
Population: Safety population included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Alkaline Phosphatase (high): Grade 3 | 5 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Alkaline Phosphatase (high): Grade 4 | 1 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Bilirubin (high): Grade 3 | 3 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Bilirubin (high): Grade 4 | 1 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Creatinine (high): Grade 3 | 1 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Creatinine (high): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Creatinine (high): Grade 3 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Alkaline Phosphatase (high): Grade 3 | 1 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Bilirubin (high): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Alkaline Phosphatase (high): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Creatinine (high): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Chemistry Parameters | Bilirubin (high): Grade 3 | 0 Participants |
Primary
Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters
The following hematology parameters were analyzed: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets. Laboratory toxicities were graded using NCI-CTCAE version 4 where, grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (potentially life threatening) and grade 5 (death) for each parameter. Number of participants with Grade 3 and 4 toxicities were reported. Low indicates values lower than the normal range.
Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
Population: Safety population included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Leukocytes (low): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Neutrophils (low): Grade 3 | 9 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Leukocytes (low): Grade 3 | 5 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Neutrophils (low): Grade 4 | 1 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Lymphocytes (low): Grade 3 | 11 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Platelets (low): Grade 3 | 4 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Hemoglobin (low): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Platelets (low): Grade 4 | 1 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Lymphocytes (low): Grade 4 | 1 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Hemoglobin (low): Grade 3 | 7 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Hemoglobin (low): Grade 3 | 16 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Hemoglobin (low): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Leukocytes (low): Grade 3 | 2 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Leukocytes (low): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Lymphocytes (low): Grade 3 | 8 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Lymphocytes (low): Grade 4 | 1 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Neutrophils (low): Grade 3 | 4 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Neutrophils (low): Grade 4 | 0 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Platelets (low): Grade 3 | 4 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With NCI-CTCAE Grade 3/4 Postbaseline Laboratory Toxicities: Hematology Parameters | Platelets (low): Grade 4 | 1 Participants |
Primary
Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death
An AE was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. Number of participants with TEAEs leading to dose reduction, permanent study drug discontinuation and death were reported.
Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
Population: Safety population included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | TEAE leading to dose reduction | 6 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | TEAE leading to permanent study drug discontinuation | 5 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | TEAE leading to death | 7 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | TEAE leading to dose reduction | 7 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | TEAE leading to permanent study drug discontinuation | 4 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With TEAEs Leading to Dose Reduction, Permanent Study Drug Discontinuation and Death | TEAE leading to death | 7 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs
An adverse event (AE) was any untoward medical occurrence in a participant administered a study drug without regard to possibility of a causal relationship. SAE was any untoward medical occurrence that at any dose resulted in death; inpatient hospitalization or prolongation of existing hospitalization; was life-threatening (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect or was considered as an important medical event. TEAEs were AEs that occurred on or after the administration of first dose of study drug through approximately 30 days after the last dose. AE included both SAEs and all non-SAEs. Treatment-related TEAEs were defined as any TEAE with at least a possible relationship to the study drug as assessed by the investigator or that was missing the assessment of causal relationship whose relationship to the study drug could not be ruled out.
Time frame: From start of study treatment up to 30 days after last dose of study treatment or before initiation of a new antineoplastic therapy, whichever occurred first (approximately maximum for 4.6 years)
Population: Safety population included all participants who received any amount of talazoparib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | TEAE | 63 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | SAE | 27 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | Treatment-related TEAEs | 45 Participants |
| Initial Dose Talazoparib: < 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | Treatment-related SAEs | 6 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | Treatment-related SAEs | 3 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | TEAE | 47 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | Treatment-related TEAEs | 31 Participants |
| Initial Dose Talazoparib: 1 mg/Day | Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs | SAE | 18 Participants |