A Phase 2, 2-Stage, 2-Cohort Study of Talazoparib (BMN 673), in Locally Advanced and/or Metastatic Breast Cancer Patients With BRCA Mutation (ABRAZO Study)

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02034916
• Collaborator: Myriad Genetic Laboratories, Inc. (Industry), Medivation, Inc. (Industry)
• Enrollment: 84
• Locations: 71
• Arm: 1
• Actual Duration (Months): 58.6
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this 2-stage, 2-cohort Phase 2 trial is to evaluate the safety and efficacy of talazoparib (also known as BMN 673) in subjects with locally advanced or metastatic breast cancer with a deleterious germline BRCA 1 or BRCA 2 mutation. Subjects will be assigned to either Cohort 1 or 2 based on prior chemotherapy for metastatic disease:

• Cohort 1) Subjects with a documented PR or CR to a prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum; or

• Cohort 2) Subjects who have received > 2 prior chemotherapy regimens for metastatic disease and who have had no prior platinum therapy for metastatic disease

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms; BRCA 1 Gene Mutation; BRCA 2 Gene Mutation	Drug: talazoparib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 84 participants
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE 2, 2-STAGE, 2-COHORT STUDY OF TALAZOPARIB (BMN 673) ADMINISTERED TO GERMLINE BRCA MUTATION SUBJECTS WITH LOCALLY ADVANCED AND/OR METASTATIC BREAST CANCER
• Actual Study Start Date: Dec 13, 2013
• Actual Primary Completion Date: Sep 1, 2016
• Actual Study Completion Date: Oct 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: talazoparib Cohort 1) Subjects with a documented PR or CR to a prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum Cohort 2) Subjects who have received > 2 prior chemotherapy regimens for metastatic disease and who have had no prior platinum therapy for metastatic disease	Drug: talazoparib; Other Names: MDV3800 BMN673

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [From randomization until data cutoff date (01 Sep 2016)]

   ORR: Percentage of participants with a confirmed best overall complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1). CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to less than (<) 10 millimeter (mm) in short axis. PR: Greater than or equal to (>=) 30 percent (%) decrease in sum of diameters of target lesions, compared to the sum at baseline. Response evaluation was done by an independent radiology facility (IRF).

Secondary Outcome Measures

1. Clinical Benefit Rate-24 (CBR-24) [From randomization until data cutoff date (01 Sep 2016)]

   CBR24: Percentage of participants with a best response of CR, PR or stable disease (SD) sustained for at least 24 weeks, as assessed by IRF using RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. SD: Neither PR nor progression of disease (PD) criteria met. SD follow PR only when sum increases by less than 20% from the nadir, but previously seen 30% decrease from baseline no longer hold. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.

2. Duration of Response (DOR) [From first documentation of CR or PR until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])]

   DOR: Time from first documentation of CR or PR, to PD by IRF assessment using RECIST 1.1, or to death due to any cause, whichever occurred first. CR: Disappearance of all non-nodal target and non-target lesions, with target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PD or death at the analysis date were censored at last tumor assessment date prior to on or before initiation of a new anticancer therapy or before the data cutoff date.

3. Progression Free Survival (PFS) [From first dose of study drug until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])]

   PFS was defined as the time in months from the first dose of study drug to the first documentation of PD by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PFS event at the analysis were censored at last tumor assessment date prior to data cutoff or date of new anticancer treatment initiation, whichever occurred first.

4. Overall Survival (OS) [From first dose of study drug until death due to any cause (up to the data cutoff date [01 Sep 2016])]

   OS was defined as the time from first dose of study drug to death due to any cause. For participants without a death date at the time of data cutoff or permanently lost to follow-up, OS was right-censored at the date the participant was last known to be alive on or before the data cutoff date.

5. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.

6. Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)]

   A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A treatment-related SAE was a treatment-related AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. Related TEAEs are TEAEs that were judged by the investigators as possibly, probably, or definitely related to study drug. AEs included both SAES and non SAES.

7. Number of Participants With Outcome in Response to Adverse Events (AEs) [Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: 'Is the AE leading to study discontinuation or death?' as 'yes'.

8. Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter) [Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)]

   Laboratory tests included hematology (hemoglobin [low], leucocytes [low], lymphocytes [low], neutrophils [low], platelets [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of participants with increase of 2 or more CTCAE toxicity grades above baseline, for hematology laboratory parameter is reported in this outcome measure.

9. Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter) [Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016])]

   Laboratory tests included serum chemistry (alanine aminotransferase [high], albumin [low], alkaline phosphatase [high], aspartate aminotransferase [high], bilirubin [high], calcium [low], glucose [high], magnesium [low], phosphate [low], potassium [high], potassium [low], sodium [high], sodium [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of participants with increase of 2 or more CTCAE toxicity grades above baseline, for chemistry laboratory parameter is reported in this outcome measure.

10. Number of Participants With Clinically Significant Change From Baseline in Vital Signs [Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)]

    Criteria for clinically significant vital signs changes: 1) Blood pressure: systolic blood pressure (SBP): greater than or equal to (>=30) millimeters of mercury (mmHg) increase from baseline, diastolic blood pressure (DBP): >=20 mmHg decrease from baseline; 2) Heart rate (HR): absolute HR greater than (>) 120 beats per minute (bpm) and >30 bpm increase from baseline, absolute HR less than (<) 50 bpm and >20 bpm decrease from baseline; 3) Weight: >10% decrease from baseline. Number of participants with any clinically significant change from baseline for blood pressure, heart rate and weight are reported in this outcome measure.

11. Number of Participants With Clinically Significant Change From Baseline in Physical Findings [Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)]

    Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.

12. Number of Participants With At Least 1 Concomitant Medication [Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)]

    Number of participants taking any non-study medications, therapies, including herbal supplements during the treatment-emergent period for the management of an adverse event or for the treatment of any other disease.

13. Trough Concentration Versus Time Summary of Talazoparib [Predose on Day 1 of Cycle 1, 2, 3, and 4 (data cutoff date: 01 Sep 2016)]

    Concentrations below the limit of quantitation values less than or equal to (<=) 25 picogram per milliliter (pg/mL) were set as zero. Pharmacokinetic (PK) analysis was not done separately for each reporting arm and cohorts were combined for PK analysis.

Other Outcome Measures

1. Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) [Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])]

   Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the functional status score and global health status/QOL score based on the EORTC-QLQ-C30, whichever occurred first. EORTC-QLQ-C30 questionnaire is a standardized instrument developed to assess the quality of life of people with cancer. EORTC-QLQ-C30 functional subscale includes 5 items: physical, role, emotional, cognitive, and social functioning. All of the single items of functional status subscale measures and global health status/QOL subscale range from 0 to 100, where higher scores represent a better level of functioning/quality of life.

2. Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23) [Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])]

   Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the symptom score based on the EORTC-QLQ-BR23, whichever occurred first. EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much) within each scale.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed carcinoma of the breast

• Locally advanced and/or metastatic disease

• Deleterious or pathogenic germline BRCA 1 or BRCA 2 mutation

• Prior chemotherapy: Cohort 1) PR or CR to prior platinum-containing regimen for metastatic disease with disease progression > 8 weeks following the last dose of platinum; or Cohort 2) > 2 prior chemotherapy regimens for metastatic disease and no prior platinum for metastatic disease

• ECOG performance status ≤ 1

• Have adequate organ function

Exclusion Criteria:

• Prior enrollment into a clinical trial of a PARP inhibitor

• CNS metastasis except adequately treated brain metastasis documented by baseline CT or MRI scan that has not progressed since previous scans and that does not require corticosteroids for management of CNS symptoms

• Prior malignancy except for prior BRCA-associated cancer as long as there is no current evidence of the prior cancer, carcinoma in situ of the cervix or non-melanoma skin cancer, and a cancer diagnosed and definitively treated >5 years prior to study enrollment with no subsequent evidence of recurrence

• Known to be HIV positive, active hepatitis C virus, or active hepatitis B virus

• Known hypersensitivity to any of the components of talazoparib

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marin Cancer Care, Inc.	Greenbrae	California	United States	94904
2	UCLA West Medical Pharmacy Attn: Steven L. Wong, PharmD	Los Angeles	California	United States	90095-1772
3	UCLA West Medical Pharmacy, Attn: Steven L. Wong, Pharm.D.	Los Angeles	California	United States	90095-7349
4	TRIO-US Central Administration	Los Angeles	California	United States	90095
5	Stanford Women's Cancer Center	Palo Alto	California	United States	94304
6	UCLA Hematology Oncology- Porter Ranch	Porter Ranch	California	United States	91326
7	Torrance Health Association, DBA Torrance Memorial Physician Network/Cancer Care Associates	Redondo Beach	California	United States	90277
8	University of California, San Francisco: Helen Diller Comprehensive Cancer Center	San Francisco	California	United States	94115
9	UCLA Hematology-Oncology	Santa Monica	California	United States	90404
10	Stanford Cancer Institute	Stanford	California	United States	94305
11	Stanford Hospital and Clinics	Stanford	California	United States	94305
12	Sylvester at Deerfield Beach	Deerfield Beach	Florida	United States	33442
13	Memorial Cancer Institute at Memorial Regional Hospital	Hollywood	Florida	United States	33021
14	Memorial Regional Hospital	Hollywood	Florida	United States	33021
15	University of Miami Hospital & Clinics	Miami	Florida	United States	33136
16	Memorial Breast Cancer Center at Memorial Hospital West	Pembroke Pines	Florida	United States	33028
17	Memorial Cancer Institute at Memorial Hospital West	Pembroke Pines	Florida	United States	33028
18	Memorial Hospital West	Pembroke Pines	Florida	United States	33028
19	Sylvester at Plantation	Plantation	Florida	United States	33324
20	ICRC	Indianapolis	Indiana	United States	46202-5116
21	Indiana University Health Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
22	Investigational Drug Services	Indianapolis	Indiana	United States	46202
23	IU Health University Hospital	Indianapolis	Indiana	United States	46202
24	Sidney & Lois Eskenazi Hospital	Indianapolis	Indiana	United States	46202
25	Springmill Medical Clinic	Indianapolis	Indiana	United States	46290
26	Anne Arundel Medical Center (AAMC), Annapolis Oncology and Hematology	Annapolis	Maryland	United States	21401
27	Anne Arundel Medical Center (AAMC), Research Pharmacy	Annapolis	Maryland	United States	21401
28	Anne Arundel Medical Center (AAMC)	Annapolis	Maryland	United States	21401
29	Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins	Baltimore	Maryland	United States	21231
30	Sidney Kimmel Comprehensive Cancer Center (SKCCC) at Johns Hopkins, Green Spring Station	Lutherville	Maryland	United States	21093
31	Memorial Sloan Kettering Evelyn H. Lauder Breast Center	New York	New York	United States	10065
32	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065
33	Memorial Sloan Kettering Rockville Centre	Rockville Centre	New York	United States	11570
34	University of Tennessee Medical Center	Knoxville	Tennessee	United States	37920
35	Tennessee Oncology, PLLC	Nashville	Tennessee	United States	37203
36	The Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
37	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
38	Centre Oscar Lambret	Lille Cédex		France	59020
39	Centre Leon Berard	Lyon Cedex 08		France	69373
40	Institut Paoli Calmettes	Marseille		France	13273 Cedex 9
41	Hopital Prive du Confluent	Nantes BP 20215		France	44202 Cedex 2
42	Hopitaux Universitaires de Strasbourg - Hopital Civil	Strasbourg		France	67091Cedex
43	Institut Universitaire du Cancer Toulouse - Oncopole	Toulouse		France	31059 Cedex 9
44	CHU Bretonneau Centre Henry Kaplan	Tours Cedex 9		France	37044
45	Universitaetsklinikum Erlangen	Erlangen	Bavaria	Germany	91054
46	IOZ Muenchen - lnerdisziplinaeres Onkologisches Zentrum	Muenchen	Bavaria	Germany	80336
47	Klinikum rechts der Isar der TU Muenchen	Muenchen	Bavaria	Germany	81675
48	University of Munich (LMU) Grosshadern Hospital	Munich	Bavaria	Germany	81377
49	Klinikum Mutterhaus Der Borromaeerinnen Ggmbh	Trier	Rheinland-pfalz	Germany	54290
50	University Hospital Carl Gustav Carus	Dresden	Saxony	Germany	01307
51	Helios Klinikum Berlin-Buch	Berlin		Germany	13125
52	University Hospital Duesseldorf	Duesseldorf		Germany	40225
53	Kliniken Essen Mitte Klinik fuer Gynaekologie und Gynaekologische Onkologie	Essen		Germany	45136
54	Universitaetsklinikum Schleswig-Holstein	Kiel		Germany	24105
55	g.SUND Gynaekologie Kompetenzzentrum Stralsund	Stralsund		Germany	18435
56	Universitaets-Frauenklinik	Tuebingen		Germany	72076
57	Complejo Hospitalario Universitario A Coruna	A Coruna		Spain	15006
58	Hospital Universitari Vall d'Hebron	Barcelona		Spain	08035
59	Complejo Hospitalario de Jaen	Jaen		Spain	23007
60	Hospital General Universitario Gregorio Maranon	Madrid		Spain	28007
61	MD Anderson Cancer Center International Espana	Madrid		Spain	28033
62	Hospital Clinico San Carlos	Madrid		Spain	28040
63	Hospital Universitario San Juan de Alicante	San Juan de Alicante		Spain	03550
64	Hospital Universitario Virgen Macarena	Sevilla		Spain	41009
65	Hospital Universitario Miguel Servet	Zaragoza		Spain	50009
66	Cambridge University Hospital NHS Foundation Trust	Cambridge	England	United Kingdom	CB2 0QQ
67	Sarah Cannon Research Institute UK	London	England	United Kingdom	W1G 6AD
68	Lancashire Teaching Hospitals NHS Foundation Trust	Preston	Lancashire	United Kingdom	PR2 9HT
69	The Royal Marsden NHS Foundation Trust	London		United Kingdom	SW3 6JJ
70	The Christie NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
71	The Royal Marsden NHS Foundation Trust	Sutton		United Kingdom	SM2 5PT

Sponsors and Collaborators

• Pfizer
• Myriad Genetic Laboratories, Inc.
• Medivation, Inc.

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02034916
• Other Study ID Numbers: 673-201; 2013-003076-12; C3441008
• First Posted: Jan 14, 2014
• Last Update Posted: Oct 14, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: Breast cancer; BRCA mutation; PARP inhibitor; BRCA 1; BRCA 2
• Additional relevant MeSH terms: Breast Neoplasms; Talazoparib

Study Results

Participant Flow

Pre-assignment Detail	In this study, enrollment of participants was to be done in 2 stages for each of the 2 cohorts. Sufficient responses in each cohort were observed such that enrollment could proceed to Stage 2 for both cohorts. However, due to Sponsor decision, enrollment in the overall trial was terminated early.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 milligram (mg) orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Period Title: Overall Study
STARTED	49	35
Treated	48	35
COMPLETED	0	0
NOT COMPLETED	49	35

Baseline Characteristics

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg	Total
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Total of all reporting groups
Overall Participants	49	35	84
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.1 (11.48)	53.4 (11.05)	51.5 (11.35)
Sex: Female, Male (Count of Participants)
Female	48 98%	34 97.1%	82 97.6%
Male	1 2%	1 2.9%	2 2.4%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR: Percentage of participants with a confirmed best overall complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors version 1.1 (RECIST 1.1). CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to less than (<) 10 millimeter (mm) in short axis. PR: Greater than or equal to (>=) 30 percent (%) decrease in sum of diameters of target lesions, compared to the sum at baseline. Response evaluation was done by an independent radiology facility (IRF).
Time Frame	From randomization until data cutoff date (01 Sep 2016)

Outcome Measure Data

Analysis Population Description

Tumor-evaluable population (TEP) included all treated participants who had a baseline and at least 1 post-baseline tumor assessment or who discontinued the study before first scheduled post-baseline tumor scan plus (+) 1 week window.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
Number (95% Confidence Interval) [percentage of participants]	20.8 42.4%	37.1 106%

2. Secondary Outcome

Title	Clinical Benefit Rate-24 (CBR-24)
Description	CBR24: Percentage of participants with a best response of CR, PR or stable disease (SD) sustained for at least 24 weeks, as assessed by IRF using RECIST 1.1. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. SD: Neither PR nor progression of disease (PD) criteria met. SD follow PR only when sum increases by less than 20% from the nadir, but previously seen 30% decrease from baseline no longer hold. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.
Time Frame	From randomization until data cutoff date (01 Sep 2016)

Outcome Measure Data

Analysis Population Description

TEP included all treated participants who had a baseline and at least 1 post-baseline tumor assessment or who discontinued the study before first scheduled post-baseline tumor scan + 1 week window.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
Number (95% Confidence Interval) [percentage of participants]	27.1 55.3%	45.7 130.6%

3. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR: Time from first documentation of CR or PR, to PD by IRF assessment using RECIST 1.1, or to death due to any cause, whichever occurred first. CR: Disappearance of all non-nodal target and non-target lesions, with target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PD or death at the analysis date were censored at last tumor assessment date prior to on or before initiation of a new anticancer therapy or before the data cutoff date.
Time Frame	From first documentation of CR or PR until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])

Outcome Measure Data

Analysis Population Description

TEP included all treated participants who had a baseline and at least 1 post-baseline tumor assessment or who discontinued the study before first scheduled post-baseline tumor scan + 1 week window. Here 'Number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	10	13
Median (95% Confidence Interval) [months]	5.8	3.8

4. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	PFS was defined as the time in months from the first dose of study drug to the first documentation of PD by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions. Participants with no PFS event at the analysis were censored at last tumor assessment date prior to data cutoff or date of new anticancer treatment initiation, whichever occurred first.
Time Frame	From first dose of study drug until PD, last tumor assessment without PD before new anticancer treatment initiation or death due to any cause, whichever occurred first (up to the data cutoff date [01 Sep 2016])

Outcome Measure Data

Analysis Population Description

ITT population involved all enrolled participants including participants who were not treated.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	49	35
Median (95% Confidence Interval) [months]	4.0	5.6

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from first dose of study drug to death due to any cause. For participants without a death date at the time of data cutoff or permanently lost to follow-up, OS was right-censored at the date the participant was last known to be alive on or before the data cutoff date.
Time Frame	From first dose of study drug until death due to any cause (up to the data cutoff date [01 Sep 2016])

Outcome Measure Data

Analysis Population Description

ITT population involved all enrolled participants including participants who were not treated.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	49	35
Median (95% Confidence Interval) [months]	11.8	16.5

6. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both serious and non-serious AEs.
Time Frame	Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
AEs	47 95.9%	34 97.1%
SAEs	16 32.7%	7 20%

7. Secondary Outcome

Title	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	A treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. A treatment-related SAE was a treatment-related AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; an important medical event or reaction, including events requiring medical intervention to prevent worsening to any of the previously noted seriousness criteria. Related TEAEs are TEAEs that were judged by the investigators as possibly, probably, or definitely related to study drug. AEs included both SAES and non SAES.
Time Frame	Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
AEs	46 93.9%	33 94.3%
SAEs	7 14.3%	4 11.4%

8. Secondary Outcome

Title	Number of Participants With Outcome in Response to Adverse Events (AEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Outcome of an AE was response to a question answered by the investigator: 'Is the AE leading to study discontinuation or death?' as 'yes'.
Time Frame	Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
AEs leading to study drug discontinuation	4 8.2%	1 2.9%
AEs leading to death	5 10.2%	1 2.9%

9. Secondary Outcome

Title	Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Hematology Parameter)
Description	Laboratory tests included hematology (hemoglobin [low], leucocytes [low], lymphocytes [low], neutrophils [low], platelets [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of participants with increase of 2 or more CTCAE toxicity grades above baseline, for hematology laboratory parameter is reported in this outcome measure.
Time Frame	Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
Hemoglobin (low)	19 38.8%	16 45.7%
Leukocytes (low)	16 32.7%	15 42.9%
Lymphocytes (low)	15 30.6%	4 11.4%
Neutrophils (low)	20 40.8%	17 48.6%
Platelets (low)	21 42.9%	10 28.6%

10. Secondary Outcome

Title	Number of Participants With Toxicity Grades Increase of 2 or More in Laboratory Parameter (Chemistry Parameter)
Description	Laboratory tests included serum chemistry (alanine aminotransferase [high], albumin [low], alkaline phosphatase [high], aspartate aminotransferase [high], bilirubin [high], calcium [low], glucose [high], magnesium [low], phosphate [low], potassium [high], potassium [low], sodium [high], sodium [low]). Toxicity grades were evaluated based on national cancer institute- common terminology criteria for adverse events (NCI-CTCAE) version 4.03. Number of participants with increase of 2 or more CTCAE toxicity grades above baseline, for chemistry laboratory parameter is reported in this outcome measure.
Time Frame	Baseline up to 30 days after the last dose of study drug or before initiation of a new anticancer treatment, whichever occurred first (up to data cutoff date [01 Sep 2016])

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
Alanine aminotransferase (high)	3 6.1%	2 5.7%
Albumin (low)	3 6.1%	0 0%
Alkaline phosphatase (high)	1 2%	1 2.9%
Aspartate aminotransferase (high)	2 4.1%	1 2.9%
Bilirubin (high)	2 4.1%	0 0%
Calcium (low)	4 8.2%	1 2.9%
Glucose (high)	1 2%	1 2.9%
Magnesium (low)	1 2%	0 0%
Phosphate (low)	6 12.2%	2 5.7%
Potassium (high)	1 2%	0 0%
Potassium (low)	2 4.1%	0 0%
Sodium (high)	1 2%	0 0%
Sodium (low)	0 0%	1 2.9%

11. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Description	Criteria for clinically significant vital signs changes: 1) Blood pressure: systolic blood pressure (SBP): greater than or equal to (>=30) millimeters of mercury (mmHg) increase from baseline, diastolic blood pressure (DBP): >=20 mmHg decrease from baseline; 2) Heart rate (HR): absolute HR greater than (>) 120 beats per minute (bpm) and >30 bpm increase from baseline, absolute HR less than (<) 50 bpm and >20 bpm decrease from baseline; 3) Weight: >10% decrease from baseline. Number of participants with any clinically significant change from baseline for blood pressure, heart rate and weight are reported in this outcome measure.
Time Frame	Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
Blood pressure (SBP or DBP)	20 40.8%	18 51.4%
HR	2 4.1%	0 0%
Weight	4 8.2%	1 2.9%

12. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Physical Findings
Description	Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant reported symptoms. Findings were considered to be clinically significant based on investigator's decision.
Time Frame	Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
Count of Participants [Participants]	0 0%	0 0%

13. Secondary Outcome

Title	Number of Participants With At Least 1 Concomitant Medication
Description	Number of participants taking any non-study medications, therapies, including herbal supplements during the treatment-emergent period for the management of an adverse event or for the treatment of any other disease.
Time Frame	Baseline up to end of study (up to a maximum duration of 42.8 months): based on data cutoff date (31 Oct 2018)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	48	35
Count of Participants [Participants]	48 98%	34 97.1%

14. Secondary Outcome

Title	Trough Concentration Versus Time Summary of Talazoparib
Description	Concentrations below the limit of quantitation values less than or equal to (<=) 25 picogram per milliliter (pg/mL) were set as zero. Pharmacokinetic (PK) analysis was not done separately for each reporting arm and cohorts were combined for PK analysis.
Time Frame	Predose on Day 1 of Cycle 1, 2, 3, and 4 (data cutoff date: 01 Sep 2016)

Outcome Measure Data

Analysis Population Description

PK population included all participants who received at least 1 dose of talazoparib and had evaluable PK assessments. Here 'n' signifies participants evaluable for each specified categories.

Arm/Group Title	Cohort 1 + Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants, who either responded to a prior platinum-containing treatment for metastatic breast cancer or had more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. For the participants with non-platinum chemotherapy, prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	83
Day 1 of Cycle 1	10.3 (93.3)
Day 1 of Cycle 2	4340 (2360)
Day 1 of Cycle 3	4510 (2720)
Day 1 of Cycle 4	3660 (1690)

15. Other Pre-specified Outcome

Title	Time to Deterioration in Global Health Status/Quality of Life (QOL) and Functional Status as Assessed by European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Description	Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the functional status score and global health status/QOL score based on the EORTC-QLQ-C30, whichever occurred first. EORTC-QLQ-C30 questionnaire is a standardized instrument developed to assess the quality of life of people with cancer. EORTC-QLQ-C30 functional subscale includes 5 items: physical, role, emotional, cognitive, and social functioning. All of the single items of functional status subscale measures and global health status/QOL subscale range from 0 to 100, where higher scores represent a better level of functioning/quality of life.
Time Frame	Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])

Outcome Measure Data

Analysis Population Description

ITT population involved all enrolled participants including participants who were not treated.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	49	35
Global Health Status/QOL	2.8 (18.33)	5.5 (32.81)
Physical Functioning	3.1 (15.84)	5.6 (21.60)
Role Functioning	2.1 (15.43)	4.2 (31.67)
Emotional Functioning	2.7 (19.29)	5.5 (24.45)
Cognitive Functioning	2.7 (21.36)	4.2 (15.47)
Social Functioning	2.2 (19.42)	5.3 (23.57)

16. Other Pre-specified Outcome

Title	Time to Deterioration in Disease Specific Symptoms as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC-QLQ-BR23)
Description	Time to deterioration was defined as the time from baseline to day to death, first occurrence of progression, or a >=10 point change from baseline in any of the symptom score based on the EORTC-QLQ-BR23, whichever occurred first. EORTC-QLQ-BR23 is a disease-specific module for breast cancer developed as a supplement for the EORTC-QLQ-C30 to assess the quality of life of participants with breast cancer. EORTC-QLQ-BR23 symptoms subscale includes 4 items: systemic therapy side effects, breast symptoms, arm symptoms, upset by hair loss. Each item is rated by choosing 1 of 4 possible responses that record the level of intensity (1= not at all, 2= a little, 3= quite a bit, and 4= very much) within each scale.
Time Frame	Baseline up to death, disease progression or end of treatment (30 days after last dose of study drug or before initiation of a new anticancer therapy, whichever occurred first [up to data cutoff date: 01 Sep 2016])

Outcome Measure Data

Analysis Population Description

ITT population involved all enrolled participants including participants who were not treated.

Arm/Group Title	Cohort 1: Talazoparib 1 mg	Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.	Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
Measure Participants	49	35
Systemic Therapy Side Effects	2.8 (5.69)	5.5 (11.93)
Breast Symptoms	3.1 (9.71)	5.6 (28.50)
Arm Symptoms	2.6 (8.27)	4.2 (8.07)
Upset by Hair Loss	4.0	5.6

Adverse Events

Time Frame	Baseline up to end of study (up to maximum duration of 42.8 months)
Adverse Event Reporting Description	Same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. AEs and SAEs were collected for safety population.
Arm/Group Title	Cohort 1: Talazoparib 1 mg		Cohort 2: Talazoparib 1 mg
Arm/Group Description	Participants who responded to a prior platinum-containing treatment for metastatic breast cancer, with disease progression of at least 8 weeks following the last dose of platinum, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.		Participants with more than 2 prior non-platinum chemotherapy treatment for metastatic breast cancer, received talazoparib 1.0 mg orally, once daily for 21 days in repeated 21-day cycles until disease progression, occurrence of unacceptable toxicity or permanent treatment discontinuation. Prior adjuvant or neo-adjuvant therapy with a platinum was allowed if first disease recurrence was for more than 6 months since last dose of adjuvant/neo-adjuvant platinum treatment. Participants were followed-up for survival and new anticancer treatment at every 60 days after the last dose of study drug for the first year, every 90 days thereafter.
All Cause Mortality
	Cohort 1: Talazoparib 1 mg		Cohort 2: Talazoparib 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1: Talazoparib 1 mg		Cohort 2: Talazoparib 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/48 (33.3%)		7/35 (20%)
Blood and lymphatic system disorders
Anaemia	5/48 (10.4%)		1/35 (2.9%)
Thrombocytopenia	2/48 (4.2%)		1/35 (2.9%)
Anaemia of malignant disease	1/48 (2.1%)		0/35 (0%)
Gastrointestinal disorders
Oesophagitis	1/48 (2.1%)		0/35 (0%)
Infections and infestations
Influenza	0/48 (0%)		1/35 (2.9%)
Neutropenic sepsis	0/48 (0%)		1/35 (2.9%)
Pneumonia	2/48 (4.2%)		0/35 (0%)
Injury, poisoning and procedural complications
Transfusion reaction	1/48 (2.1%)		0/35 (0%)
Investigations
Platelet count decreased	1/48 (2.1%)		1/35 (2.9%)
Metabolism and nutrition disorders
Hypokalaemia	1/48 (2.1%)		0/35 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/48 (2.1%)		0/35 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm progression	3/48 (6.3%)		0/35 (0%)
Breast cancer metastatic	2/48 (4.2%)		0/35 (0%)
Silicon granuloma	1/48 (2.1%)		0/35 (0%)
Nervous system disorders
Central nervous system lesion	1/48 (2.1%)		0/35 (0%)
Presyncope	1/48 (2.1%)		0/35 (0%)
Syncope	1/48 (2.1%)		0/35 (0%)
Psychiatric disorders
Anxiety	1/48 (2.1%)		0/35 (0%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	3/48 (6.3%)		2/35 (5.7%)
Dyspnoea	2/48 (4.2%)		2/35 (5.7%)
Atelectasis	1/48 (2.1%)		0/35 (0%)
Pulmonary embolism	1/48 (2.1%)		0/35 (0%)
Respiratory distress	0/48 (0%)		1/35 (2.9%)
Surgical and medical procedures
Lipoinjection	1/48 (2.1%)		0/35 (0%)
Salpingo-oophorectomy	1/47 (2.1%)		0/34 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1: Talazoparib 1 mg		Cohort 2: Talazoparib 1 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/48 (97.9%)		34/35 (97.1%)
Blood and lymphatic system disorders
Anaemia	23/48 (47.9%)		19/35 (54.3%)
Leukopenia	7/48 (14.6%)		6/35 (17.1%)
Lymphopenia	2/48 (4.2%)		4/35 (11.4%)
Neutropenia	10/48 (20.8%)		12/35 (34.3%)
Thrombocytopenia	18/48 (37.5%)		9/35 (25.7%)
Cardiac disorders
Tachycardia	2/48 (4.2%)		2/35 (5.7%)
Gastrointestinal disorders
Abdominal discomfort	1/48 (2.1%)		2/35 (5.7%)
Abdominal distension	1/48 (2.1%)		3/35 (8.6%)
Abdominal pain	7/48 (14.6%)		7/35 (20%)
Abdominal pain upper	2/48 (4.2%)		6/35 (17.1%)
Constipation	9/48 (18.8%)		6/35 (17.1%)
Diarrhoea	18/48 (37.5%)		10/35 (28.6%)
Dry mouth	0/48 (0%)		2/35 (5.7%)
Dyspepsia	5/48 (10.4%)		3/35 (8.6%)
Nausea	20/48 (41.7%)		15/35 (42.9%)
Stomatitis	3/48 (6.3%)		1/35 (2.9%)
Toothache	1/48 (2.1%)		2/35 (5.7%)
Vomiting	10/48 (20.8%)		8/35 (22.9%)
General disorders
Asthenia	3/48 (6.3%)		10/35 (28.6%)
Axillary pain	1/48 (2.1%)		2/35 (5.7%)
Fatigue	29/48 (60.4%)		8/35 (22.9%)
Mucosal inflammation	4/48 (8.3%)		2/35 (5.7%)
Non-cardiac chest pain	3/48 (6.3%)		0/35 (0%)
Oedema peripheral	1/48 (2.1%)		6/35 (17.1%)
Pyrexia	1/48 (2.1%)		5/35 (14.3%)
Chills	1/48 (2.1%)		2/35 (5.7%)
Infections and infestations
Gingivitis	0/48 (0%)		2/35 (5.7%)
Influenza	3/48 (6.3%)		1/35 (2.9%)
Lower respiratory tract infection	3/48 (6.3%)		0/35 (0%)
Nasopharyngitis	0/48 (0%)		2/35 (5.7%)
Pharyngitis	0/48 (0%)		3/35 (8.6%)
Rhinitis	4/48 (8.3%)		2/35 (5.7%)
Sinusitis	1/48 (2.1%)		2/35 (5.7%)
Upper respiratory tract infection	3/48 (6.3%)		5/35 (14.3%)
Oral herpes	0/48 (0%)		2/35 (5.7%)
Viral upper respiratory tract infection	11/48 (22.9%)		3/35 (8.6%)
Investigations
Alanine aminotransferase increased	1/48 (2.1%)		3/35 (8.6%)
Aspartate aminotransferase increased	4/48 (8.3%)		2/35 (5.7%)
Neutrophil count decreased	5/48 (10.4%)		5/35 (14.3%)
Platelet count decreased	7/48 (14.6%)		5/35 (14.3%)
Weight decreased	3/48 (6.3%)		0/35 (0%)
White blood cell count decreased	3/48 (6.3%)		5/35 (14.3%)
Metabolism and nutrition disorders
Decreased appetite	12/48 (25%)		10/35 (28.6%)
Hyperglycaemia	2/48 (4.2%)		2/35 (5.7%)
Hypomagnesaemia	3/48 (6.3%)		0/35 (0%)
Hyponatraemia	1/48 (2.1%)		2/35 (5.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/48 (16.7%)		9/35 (25.7%)
Back pain	12/48 (25%)		8/35 (22.9%)
Bone pain	0/48 (0%)		2/35 (5.7%)
Muscle spasms	4/48 (8.3%)		5/35 (14.3%)
Musculoskeletal chest pain	3/48 (6.3%)		2/35 (5.7%)
Musculoskeletal pain	1/48 (2.1%)		3/35 (8.6%)
Neck pain	1/48 (2.1%)		3/35 (8.6%)
Pain in extremity	2/48 (4.2%)		3/35 (8.6%)
Myalgia	1/48 (2.1%)		2/35 (5.7%)
Nervous system disorders
Dizziness	6/48 (12.5%)		2/35 (5.7%)
Dysgeusia	1/48 (2.1%)		3/35 (8.6%)
Headache	9/48 (18.8%)		11/35 (31.4%)
Neuralgia	0/48 (0%)		2/35 (5.7%)
Neuropathy peripheral	2/48 (4.2%)		4/35 (11.4%)
Presyncope	0/48 (0%)		2/35 (5.7%)
Psychiatric disorders
Depression	1/48 (2.1%)		2/35 (5.7%)
Insomnia	5/48 (10.4%)		3/35 (8.6%)
Anxiety	2/48 (4.2%)		2/35 (5.7%)
Respiratory, thoracic and mediastinal disorders
Cough	9/48 (18.8%)		7/35 (20%)
Dyspnoea	9/48 (18.8%)		9/35 (25.7%)
Epistaxis	2/48 (4.2%)		2/35 (5.7%)
Nasal congestion	1/48 (2.1%)		2/35 (5.7%)
Pleural effusion	1/48 (2.1%)		2/35 (5.7%)
Rhinorrhoea	0/48 (0%)		3/35 (8.6%)
Oropharyngeal pain	2/48 (4.2%)		3/35 (8.6%)
Skin and subcutaneous tissue disorders
Alopecia	11/48 (22.9%)		6/35 (17.1%)
Dry skin	1/48 (2.1%)		4/35 (11.4%)
Erythema	0/48 (0%)		3/35 (8.6%)
Pruritus	1/48 (2.1%)		3/35 (8.6%)
Hyperhidrosis	1/48 (2.1%)		2/35 (5.7%)
Vascular disorders
Hot flush	3/48 (6.3%)		3/35 (8.6%)
Lymphoedema	3/48 (6.3%)		2/35 (5.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.