Breast Neoplasms, Neoplasms
Conditions
Keywords
Phase 1, talazoparib, PF-06944076, MDV3800, BMN673, PARP inhibitor, Japanese, solid tumors, breast cancer, C3441030
Brief summary
This is a Phase 1 study which consists of 2 parts; Dose Escalation part and Expansion part. The dose escalation part is open-label, and evaluates safety, preliminary efficacy and PK of single-agent talazoparib in sequential cohorts of adult patients with advanced solid tumors who are resistant to standard therapy or for whom no standard therapy is available. In the dose escalation part, up to 18 (minimum 3) patients are expected to be enrolled depending on the observed DLTs. The expansion part is designed to assess the efficacy, safety and PK of single-agent talazoparib at RP2D determined in the dose escalation part in adult patients with locally advanced or metastatic breast cancer who have deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations. In the expansion part, a minimum of 17 patients will be enrolled evaluable for the primary endpoint.
Interventions
DRUGtalazoparib
Talazoparib will be administered orally on a continuous basis. Talazoparib may be taken with or without food. Each cycle will consist of 28 days.
Sponsors
Pfizer
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\[Dose Escalation Part\] 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
* Patients with known symptomatic brain metastases requiring steroids. * Current use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP within 1 week or 5 half lives which ever is longer prior to the first dose of study treatment. * Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception. \[Dose Expansion Part\] Inclusion Criteria: * Histologically or cytologically confirmed carcinoma of the breast. * Locally advanced breast cancer that is not amenable to curative radiation or surgery and/or metastatic disease. * Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation by Myriad Genetics' BRACAnalysis CDx test. * No more than 3 prior chemotherapy-inclusive regimens for locally advanced or metastatic disease. * Have measurable lesion by the RECIST v.1.1. * ECOG Performance Status 0-2. * Adequate Bone Marrow, Renal and Liver Function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) | Cycle 1 (28 days) | DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (\>)7days; Febrile neutropenia \>1 hour; G greater than or equal to (\>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for \>=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G\>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G\>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)\>5\*upper limit of normal(ULN) and 2\*increases above baseline values; ALT/AST\>=3\*ULN concurrent with total bilirubin (TB)\>2\*ULN; TB\>5\*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib. |
| Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) | Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher AEs were reported. |
| Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days | Parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure. |
| Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days | Hematological parameters included: Anemia, Hemoglobin increased, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure. |
| Dose Escalation: Number of Participants With Abnormalities in Vital Signs | Baseline up to 286 days | Vital sign abnormalities: a) Sitting systolic blood pressure: \<90 millimeter of mercury (mmHg), decrease from baseline \>=30 mmHg, increase from baseline \>=30 mmHg; b) Sitting diastolic blood pressure: minimum \<50 mmHg, decrease from baseline \>=20 mmHg, increase from baseline \>=20 mmHg; c) Sitting pulse rate: minimum \<40 beats per minute (bpm), maximum \>120 bpm. Only those categories in which at least one participant had data were reported in this outcome measure. |
| Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 | Cmax was defined as the maximum observed plasma concentration of talazoparib. |
| Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 | Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib. |
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 | Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast). |
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day -7 of Cycle 1 | Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours. |
| Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F) | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 | Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. |
| Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. |
| Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 | Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. |
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1 | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf). |
| Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 | Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib. |
| Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib | Pre dose on Day 22 of Cycle 1 | Pre dose plasma concentration of talazoparib. |
| Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 | Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose). |
| Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 | Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours. |
| Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) | Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. |
| Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib | Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day -7 and Day 22 of Cycle 1 | Accumulation ratio for AUC was calculated as AUCtau for Day 22 divided by AUCtau for Day -7, where AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. |
| Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1; Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 | Rss was calculated by dividing AUCtau at steady state (post multiple dosing on Day 22) by single dose AUCinf (on Day -7). AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). |
| Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 286 days) | OR in participants was defined as the percentage of participants with CR or PR as best response determined by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Dose Escalation: Progression Free Survival (PFS) | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 286 days) | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion. |
| Dose Escalation: Duration of Response (DOR) | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 286 days) | DOR was defined as the time between the date of the first documented objective response (PR or CR) and the date of the first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. |
| Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) | Confirmed OR in participants was defined as the percentage of participants with CR or PR as best response determined by BICR as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Baseline up to Week 16, Baseline up to Week 24 | Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. |
| Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | Baseline up to Week 16, Baseline up to Week 24 | Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by BICR as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study. |
| Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days) | TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days) | TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by BICR according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) | DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. |
| Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days) | DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. |
| Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days) | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion. |
| Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days) | PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion. |
| Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12 | At Month 12 | OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at Month 12. Probability of participants who were event free at Month 12 was estimated by Kaplan-Meier method and reported. |
| Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib | Pre dose at 0 hour on Day 1 of Cycle 2, 3, 4 and unplanned (any time during dose expansion period up to 502 days) | Pre dose plasma drug concentration. |
| Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss) | Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1 | Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. |
| Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days) | A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. AE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Relatedness to study drug was assessed by the investigator. |
Countries
Japan
Participant flow
Recruitment details
This study included 2 periods: dose escalation and dose expansion. The recommended dose for dose expansion period of talazoparib was determined in dose escalation period.
Pre-assignment details
Dose escalation period: total 9 participants were screened, enrolled into the study and assigned to study treatment. Dose expansion period: total 22 participants were screened, out of which 3 participants were screen failure. 19 participants actually enrolled into the study and assigned to study treatment. Data reported based on the primary completion date of 11 January 2021.
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation: Talazoparib 0.75 mg Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 0.75 mg orally, QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 0.75 mg talazoparib on Day -7. | 3 |
| Dose Escalation: Talazoparib 1.0 mg Participants with advanced solid tumors who were resistant to standard therapy or for whom no standard therapy was available, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle (except Cycle 1 with 7 additional days lead-in) until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 286 days). Cycle 1 contained a 7 day lead-in phase in which participants received single dose of 1.0 mg talazoparib on Day -7. | 6 |
| Dose Expansion: Talazoparib 1.0 mg Participants with gBRCAm HER2-negative locally advanced or metastatic breast cancer, received talazoparib capsules at a dose of 1.0 mg orally QD in each 28-day treatment cycle until disease progression, unacceptable toxicity or withdrawal of consent (maximum duration: up to 502 days). | 19 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Dose Escalation Period (Up to 286 Days) | Global Deterioration of Health Status | 1 | 0 | 0 |
| Dose Escalation Period (Up to 286 Days) | Progressive Disease | 2 | 6 | 0 |
| Dose Expansion Period (Up to 502 Days) | Ongoing | 0 | 0 | 8 |
| Dose Expansion Period (Up to 502 Days) | Progressive Disease | 0 | 0 | 11 |
Baseline characteristics
| Characteristic | Total | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|---|
| Age, Customized 18-44 Years | 8 Participants | 1 Participants | 0 Participants | 7 Participants |
| Age, Customized 45-64 Years | 10 Participants | 1 Participants | 3 Participants | 6 Participants |
| Age, Customized Greater than or equal to (>=)65 Years | 10 Participants | 1 Participants | 3 Participants | 6 Participants |
| Age, Customized Less than (<)18 Years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 3 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 28 Participants | 3 Participants | 6 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 24 Participants | 2 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 3 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 6 | 2 / 19 |
| other Total, other adverse events | 3 / 3 | 6 / 6 | 19 / 19 |
| serious Total, serious adverse events | 1 / 3 | 0 / 6 | 1 / 19 |
Outcome results
Primary
Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT)
DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (\>)7days; Febrile neutropenia \>1 hour; G greater than or equal to (\>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for \>=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G\>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G\>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)\>5\*upper limit of normal(ULN) and 2\*increases above baseline values; ALT/AST\>=3\*ULN concurrent with total bilirubin (TB)\>2\*ULN; TB\>5\*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib.
Time frame: Cycle 1 (28 days)
Population: The per-protocol analysis set included all enrolled participants who received at least 1 dose of study treatment and who did not have major treatment deviations during the first cycle. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 Participants |
Primary
Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment | 57.9 Percentage of participants |
Secondary
Dose Escalation: Duration of Response (DOR)
DOR was defined as the time between the date of the first documented objective response (PR or CR) and the date of the first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)
Population: Due to no participants with response in dose escalation period, data collection and analysis for DOR was not performed. Hence, data is not reported.
Secondary
Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib
Accumulation ratio for AUC was calculated as AUCtau for Day 22 divided by AUCtau for Day -7, where AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours.
Time frame: Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day -7 and Day 22 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib | 2.734 Ratio | Geometric Coefficient of Variation 24 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib | 2.866 Ratio | Geometric Coefficient of Variation 64 |
Secondary
Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss)
Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss) | 5.898 Liter per hour | Geometric Coefficient of Variation 7 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss) | 4.086 Liter per hour | Geometric Coefficient of Variation 21 |
Secondary
Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib
Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib | 127.2 Nanogram hour per milliliter | Geometric Coefficient of Variation 6 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib | 244.7 Nanogram hour per milliliter | Geometric Coefficient of Variation 21 |
Secondary
Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib
Rss was calculated by dividing AUCtau at steady state (post multiple dosing on Day 22) by single dose AUCinf (on Day -7). AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1; Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here overall number of participants analyzed signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib | 1.181 Ratio | Geometric Coefficient of Variation 12 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib | 1.249 Ratio | Geometric Coefficient of Variation 14 |
Secondary
Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib
Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib | 14.44 Nanogram per milliliter | Geometric Coefficient of Variation 26 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib | 32.84 Nanogram per milliliter | Geometric Coefficient of Variation 14 |
Secondary
Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib
Pre dose plasma concentration of talazoparib.
Time frame: Pre dose on Day 22 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib | 2.175 Nanogram per milliliter | Geometric Coefficient of Variation 8 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib | 3.645 Nanogram per milliliter | Geometric Coefficient of Variation 49 |
Secondary
Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib
Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose).
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib | 1.02 Hours |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib | 1.03 Hours |
Secondary
Dose Escalation: Number of Participants With Abnormalities in Vital Signs
Vital sign abnormalities: a) Sitting systolic blood pressure: \<90 millimeter of mercury (mmHg), decrease from baseline \>=30 mmHg, increase from baseline \>=30 mmHg; b) Sitting diastolic blood pressure: minimum \<50 mmHg, decrease from baseline \>=20 mmHg, increase from baseline \>=20 mmHg; c) Sitting pulse rate: minimum \<40 beats per minute (bpm), maximum \>120 bpm. Only those categories in which at least one participant had data were reported in this outcome measure.
Time frame: Baseline up to 286 days
Population: The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Number of Participants With Abnormalities in Vital Signs | Systolic blood pressure: <90 mmHg | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Number of Participants With Abnormalities in Vital Signs | Systolic blood pressure: decrease from baseline >=30 mmHg | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation: Number of Participants With Abnormalities in Vital Signs | Systolic blood pressure: <90 mmHg | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation: Number of Participants With Abnormalities in Vital Signs | Systolic blood pressure: decrease from baseline >=30 mmHg | 2 Participants |
Secondary
Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
OR in participants was defined as the percentage of participants with CR or PR as best response determined by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 0 Percentage of participants |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 0 Percentage of participants |
Secondary
Dose Escalation: Progression Free Survival (PFS)
PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion.
Time frame: From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 286 days)
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Progression Free Survival (PFS) | 3.0 Months |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation: Progression Free Survival (PFS) | 3.4 Months |
Secondary
Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F)
Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here overall number of participants analyzed signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F) | 6.968 Liter per hour | Geometric Coefficient of Variation 12 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F) | 5.010 Liter per hour | Geometric Coefficient of Variation 9 |
Secondary
Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here overall number of participants analyzed signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib | 551.8 Liter | Geometric Coefficient of Variation 42 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib | 361.1 Liter | Geometric Coefficient of Variation 20 |
Secondary
Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf).
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here overall number of participants analyzed signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib | 107.5 Nanogram hour per milliliter | Geometric Coefficient of Variation 12 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib | 199.7 Nanogram hour per milliliter | Geometric Coefficient of Variation 9 |
Secondary
Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib
Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib | 97.48 Nanogram hour per milliliter | Geometric Coefficient of Variation 17 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib | 159.1 Nanogram hour per milliliter | Geometric Coefficient of Variation 33 |
Secondary
Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib
Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day -7 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib | 46.55 Nanogram hour per milliliter | Geometric Coefficient of Variation 20 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib | 85.39 Nanogram hour per milliliter | Geometric Coefficient of Variation 44 |
Secondary
Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib
Cmax was defined as the maximum observed plasma concentration of talazoparib.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Population: The Pharmacokinetic (PK) parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib | 7.244 Nanogram per milliliter | Geometric Coefficient of Variation 34 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib | 13.78 Nanogram per milliliter | Geometric Coefficient of Variation 26 |
Secondary
Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib
Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Here overall number of participants analyzed signifies participants evaluable for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib | 56.60 Hours | Standard Deviation 17.86 |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib | 50.73 Hours | Standard Deviation 10.121 |
Secondary
Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
Time frame: Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Population: The PK parameter analysis set included all enrolled participants treated who had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest in the dose escalation period only. Data for this outcome measure was not planned to be collected and analyzed for dose expansion period, as pre-specified in protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib | 0.983 Hours |
| Dose Escalation: Talazoparib 1.0 mg | Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib | 0.967 Hours |
Secondary
Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Population: Analysis was performed on subset of participants with OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | 6.0 Months |
Secondary
Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
Time frame: From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Population: Analysis was performed on subset of participants with OR.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 6.8 Months |
Secondary
Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12
OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at Month 12. Probability of participants who were event free at Month 12 was estimated by Kaplan-Meier method and reported.
Time frame: At Month 12
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12 | 0.847 Probability of event free participants |
Secondary
Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by BICR as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.
Time frame: Baseline up to Week 16, Baseline up to Week 24
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | Up to Week 16 | 89.5 Percentage of participants |
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | Up to Week 24 | 89.5 Percentage of participants |
Secondary
Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.
Time frame: Baseline up to Week 16, Baseline up to Week 24
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Up to Week 16 | 94.7 Percentage of participants |
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Up to Week 24 | 94.7 Percentage of participants |
Secondary
Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
Confirmed OR in participants was defined as the percentage of participants with CR or PR as best response determined by BICR as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | 52.6 Percentage of participants |
Secondary
Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion.
Time frame: From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | 7.2 Months |
Secondary
Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion.
Time frame: From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)
Population: FAS included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 7.2 Months |
Secondary
Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)
TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by BICR according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)
Population: Analysis was performed on subset of participants with OR. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | 2.07 Months |
Secondary
Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)
Population: Analysis was performed on subset of participants with OR. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 2.63 Months |
Secondary
Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib
Pre dose plasma drug concentration.
Time frame: Pre dose at 0 hour on Day 1 of Cycle 2, 3, 4 and unplanned (any time during dose expansion period up to 502 days)
Population: The PK concentration analysis set included all enrolled participants who were treated and have at least 1 analyte concentration. Here number analyzed signifies number of participants evaluated for given time point. Data for this outcome measure was not planned to be collected and analyzed for dose escalation period, as pre-specified in protocol.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib | Cycle 2 Day 1 | 3098 Picogram per milliliter | Geometric Coefficient of Variation 40 |
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib | Cycle 3 Day 1 | 3423 Picogram per milliliter | Geometric Coefficient of Variation 41 |
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib | Cycle 4 Day 1 | 2910 Picogram per milliliter | Geometric Coefficient of Variation 52 |
| Dose Escalation: Talazoparib 0.75 mg | Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib | Unplanned | 3670 Picogram per milliliter | Geometric Coefficient of Variation 38 |
Secondary
Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03
AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher AEs were reported.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Population: The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 2 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 11 Participants |
Secondary
Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry
Parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.
Time frame: Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days
Population: The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alanine aminotransferase increased: Grade 2 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Creatinine increased: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypomagnesemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypocalcemia: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyperglycemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Aspartate aminotransferase increased: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyponatremia: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyperkalemia: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoglycemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alkaline phosphatase increased: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypermagnesemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Blood bilirubin increased: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypophosphatemia: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypernatremia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoalbuminemia: Grade 2 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alkaline phosphatase increased: Grade 2 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoalbuminemia: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alanine aminotransferase increased: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alkaline phosphatase increased: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoalbuminemia: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoglycemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Aspartate aminotransferase increased: Grade 1 | 3 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypomagnesemia: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alanine aminotransferase increased: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyponatremia: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypophosphatemia: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Blood bilirubin increased: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Creatinine increased: Grade 1 | 6 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alanine aminotransferase increased: Grade 2 | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyperglycemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoalbuminemia: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyperkalemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypermagnesemia: Grade 1 | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alkaline phosphatase increased: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypernatremia: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypocalcemia: Grade 1 | 2 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypophosphatemia: Grade 2 | 2 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alkaline phosphatase increased: Grade 1 | 4 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alanine aminotransferase increased: Grade 2 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alkaline phosphatase increased: Grade 2 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Aspartate aminotransferase increased: Grade 1 | 7 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Blood bilirubin increased: Grade 1 | 2 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Creatinine increased: Grade 1 | 17 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyperglycemia: Grade 1 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyperkalemia: Grade 1 | 0 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypermagnesemia: Grade 1 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypernatremia: Grade 1 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoalbuminemia: Grade 1 | 6 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoalbuminemia: Grade 2 | 0 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypocalcemia: Grade 1 | 9 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypoglycemia: Grade 1 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hypomagnesemia: Grade 1 | 2 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Hyponatremia: Grade 1 | 2 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry | Alanine aminotransferase increased: Grade 1 | 8 Participants |
Secondary
Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology
Hematological parameters included: Anemia, Hemoglobin increased, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.
Time frame: Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days
Population: The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Platelet count decreased: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 3 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 3 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Neutrophil count decreased: Grade 3 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Neutrophil count decreased: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 1 | 3 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 2 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 3 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Platelet count decreased: Grade 2 | 0 Participants |
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 2 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Neutrophil count decreased: Grade 2 | 0 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 2 | 3 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 3 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 2 | 3 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 3 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Neutrophil count decreased: Grade 3 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Platelet count decreased: Grade 1 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Platelet count decreased: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 1 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 2 | 1 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 3 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Platelet count decreased: Grade 1 | 10 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 1 | 6 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 2 | 9 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Platelet count decreased: Grade 2 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 3 | 9 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 1 | 8 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 1 | 1 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Neutrophil count decreased: Grade 2 | 7 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 3 | 2 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Anemia: Grade 2 | 0 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Neutrophil count decreased: Grade 3 | 4 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | Lymphocyte count decreased: Grade 2 | 4 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology | White blood cell decreased: Grade 3 | 2 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03
Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Population: The safety analysis set (SAS) included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 3 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 6 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 19 Participants |
Secondary
Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03
A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. AE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Relatedness to study drug was assessed by the investigator.
Time frame: From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Population: The safety analysis set included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 2 Participants |
| Dose Escalation: Talazoparib 1.0 mg | Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 3 Participants |
| Dose Expansion: Talazoparib 1.0 mg | Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 19 Participants |