A Study of Talazoparib in Men With DNA Repair Defects and Metastatic Castration-Resistant Prostate Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03148795
• Collaborator: Medivation, Inc. (Industry)
• Enrollment: 128
• Locations: 120
• Arm: 1
• Anticipated Duration (Months): 62
• Patients Per Site: 1.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this international, phase 2, open-label, response rate study of talazoparib is to assess the efficacy and safety of talazoparib in men with DNA repair defects metastatic castration-resistant prostate cancer (CRPC) who previously received taxane-based chemotherapy and progressed on at least 1 novel hormonal agent (enzalutamide and/or abiraterone acetate/prednisone).

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: Talazoparib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: TALAPRO-1: A PHASE 2, OPEN-LABEL, RESPONSE RATE STUDY OF TALAZOPARIB IN MEN WITH DNA REPAIR DEFECTS AND METASTATIC CASTRATION-RESISTANT PROSTATE CANCER WHO PREVIOUSLY RECEIVED TAXANE-BASED CHEMOTHERAPY AND PROGRESSED ON AT LEAST 1 NOVEL HORMONAL AGENT (ENZALUTAMIDE AND/OR ABIRATERONE ACETATE/PREDNISONE)
• Actual Study Start Date: Jul 4, 2017
• Actual Primary Completion Date: Sep 4, 2020
• Anticipated Study Completion Date: Sep 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Talazoparib Talazoparib 1 mg daily	Drug: Talazoparib; 1 mg daily; Other Names: MDV3800

Outcome Measures

Primary Outcome Measures

1. Best Objective Response Rate (ORR) [From first dose of study drug to best overall soft tissue response CR or PR (maximum duration of 25 months)]

   Best ORR was defined as the percentage of participants with best overall soft tissue response of complete response (CR) or partial response (PR) as per RECIST1.1 by an independent central review. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 millimeter (mm). Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 percent (%) decrease in sum of diameters of target lesions taking as reference baseline sum diameters.

Secondary Outcome Measures

1. Time to Objective Response [From first dose of study drug to first objective response (maximum duration of 25 months)]

   Time to objective response was defined as the time from first dose of talazoparib to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per prostate cancer working Group 3 (PCWG3). Soft tissue response is defined as a best overall response of CR or PR per RECIST 1.1 by independent central review. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 % decrease in sum of diameters of target lesions taking as reference baseline sum diameters.

2. Duration of Response (DOR) [From the first objective evidence of soft tissue response (CR or PR, whichever is earlier) to radiographic progression or death due to any cause without evidence of radiographic progression, whichever occurs first (maximum duration of 25 months)]

   DOR was defined as the time from the first objective evidence of soft tissue response (CR or PR, whichever is earlier) per RECIST 1.1 and no evidence of confirmed bone disease progression per PCWG3 to the date of first objective evidence of radiographic progression or death due to any cause without evidence of radiographic progression, whichever occurs first. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 % decrease in sum of diameters of target lesions taking as reference baseline sum diameters.

3. Percentage of Participants With Prostate-Specific Antigen (PSA) Response of Greater Than or Equal to (>=) 50 Percent (%) [Approximately 56 months]

   Analysis is not final for this outcome measure at PCD, complete data will be posted at study completion date (SCD).

4. Percentage of Participants With Circulating Tumor Cell (CTC) Count Greater Than or Equal to (>=) 5 Circulating Tumor Cell (CTC) Per 7.5 Milliliter (mL) of Blood at Baseline Decreasing to Less Than (<) 5 CTC of Blood Any Time on Study [Approximately 56 months]

   Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

5. Percentage of Participants With Circulating Tumor Cell (CTC) Count >=1 CTC Per 7.5 mL of Blood at Baseline Decreasing to Null CTC of Blood Any Time on Study [Approximately 56 months]

   Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

6. Percentage of Participants With Circulating Tumor Cell (CTC) Count <5 CTC Per 7.5 mL of Blood at Baseline Increased Any Time on Study [Approximately 56 months]

   Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

7. Time to Prostate-Specific Antigen (PSA) Progression [Approximately 56 months]

   Time to PSA progression was defined as the time from first dose of study treatment to the date of PSA progression, which was subsequently confirmed. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

8. Radiographic Progression-Free Survival (PFS) [From date of first dose of study drug to first objective evidence of radiographic progression or death without documented radiographic progression, whichever occurs first (maximum duration of 25 months)]

   Radiographic PFS was defined as the time from date of first dose of talazoparib to first objective evidence of radiographic progression as assessed in soft tissue per modified RECIST 1.1 or confirmed progression in bone per PCWG3 guidelines by independent central review or death without documented radiographic progression, whichever occurs first.

9. Overall Survival (OS) [Approximately 56 months]

   OS was defined as the time from the first dose of study treatment to death due to any cause. For participants who were alive, OS was censored at the last contact. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

10. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Baseline up to 28 days after last dose of study drug (approximately up to 26 months)]

    An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

11. Number of Participants With Permanent Treatment Discontinuation Due to Adverse Events [Baseline up to 28 days after last dose of study drug (approximately up to 26 months)]

    Treatment discontinuation was defined as permanent cessation of study drug treatment administration.

12. Number of Participants With Clinically Significant Abnormalities in Vital Signs [Baseline up to 28 days after last dose of study drug (approximately up to 26 months)]

    Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): absolute result greater than (>) 180 mmHg and increase from baseline greater than or equal to (>=) 40 mmHg or absolute result < 90 mmHg and decrease from baseline > 30 mmHg; 2) Diastolic blood pressure (DBP) (mmHg): absolute result > 110 mmHg and increase from baseline >= 30 mmHg or absolute result < 50 mmHg and decrease from baseline > 20 mmHg or >= 20 mmHg increase from baseline; 3) Heart rate in beats per minutes (bpm): absolute result < 50 bpm and decrease from baseline > 20 bpm or absolute result > 120 bpm and increase from baseline > 30 bpm; Weight in kilogram: > 10% decrease from baseline.

13. Number of Participants With Shift in Laboratory Parameter Values (Hematology) From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline [Baseline up to 28 days after last dose of study drug (approximately up to 26 months)]

    Hematology parameters included anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.

14. Number of Participants With Shift in Laboratory Parameter Values (Chemistry) From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline [Baseline up to 28 days after last dose of study drug (approximately up to 26 months)]

    Chemistry parameters:alanine aminotransferase increased(inc), alkaline phosphatase inc, aspartate aminotransferase inc, blood bilirubin inc, chronic kidney disease, creatinine inc, gamma-glutamyl transferase (GGT) inc, hypercalcemia, hypercalcemia, hyperkalemia, hypermagnesemia, hypermagnesemia, hypermagnesemia, hypocalcemia, hypocalcemia, hypokalemia, hypomagnesemia, hypophosphatemia and hypophosphatemia. Severity was graded as G1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G2:moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G3:severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G4:life-threatening consequence, urgent intervention indicated; G5: death related to AEs.

15. Number of Participants With Dose Modification [Baseline up to 28 days after last dose of study drug (approximately up to 26 months)]

    Number of participants with dose modification due to adverse events was reported.

16. Time to Deterioration in Pain Symptom Scores [Approximately 56 months]

    Time to deterioration in pain symptom scores was assessed by brief pain inventory short form (BPI-SF). Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

17. Change From Baseline in Participant Reported Pain Scores Per BPI-SF Till End of the Study [Approximately 56 months]

    BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-SF are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

18. Change From Baseline in Patient-Reported Health-Related Quality of Life as Assessed by European Quality of Life 5-Domain 5-Level Scale (EQ-5D-5L) Scores Till End of the Study [Approximately 56 months]

    The EQ-5D-5L consists of two sections, the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression with five response levels for each dimension: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ-5D VAS is a 20 cm vertical scale where patients can mark from 0 (worst health imaginable) to 100 (best health imaginable). Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.

19. Pre-dose Plasma Concentration (Ctrough) of Talazoparib [Pre-dose at Week 1, 5, 9 and 13]

    Ctrough was defined as pre-dose plasma concentration during dosing and observed directly from data.

20. Post-dose Plasma Concentration (Ctrough) of Talazoparib [2 hours post-dose at Week 1 and 5]

    Plasma concentration was measured 2 hours after dosing and observed directly from data.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. At least 18 years of age.

2. Histologically or cytologically confirmed adenocarcinoma of the prostate without signet cell, or small cell features.

3. Patients must have measurable soft tissue disease per RECIST 1.1

4. DNA damage repair deficiency as assessed centrally by a gene mutation biomarker panel (testing of de novo or archival tumor tissue (via central laboratory) or prior historical testing (with Sponsor approval) using the Foundation Medicine, FoundationOne CDx™ NGS gene panel test.

5. Consent to a saliva sample collection for a germline comparator, unless prohibited by local regulations or ethics committee (EC) decision.

6. Serum testosterone ≤ 1.73 nmol/L (50 ng/dL) at screening.

7. Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin-releasing hormone (GnRH) agonist/antagonist (surgical or medical castration).

8. Progressive disease at study entry defined as 1 or more of the following 3 criteria:

• A minimum of 3 rising PSA values with an interval of at least 1 week between determinations. The screening central laboratory PSA value must be ≥ 2 μg/L (2 ng/mL) if qualifying solely by PSA progression.

• Soft tissue disease progression as defined by RECIST 1.1.

• Bone disease progression defined by PCWG3 with 2 or more new metastatic lesions on bone scan.

1. Metastatic disease.

2. Previous treatment with 1 or 2 chemotherapy regimens including at least 1 taxane-based regimen for metastatic (non castrate or castrate) prostate cancer. Patients may have received radium-223 and/or cabazitaxel, or were deemed unsuitable, declined, or did not have access to these therapies.

3. Documented disease progression (either radiographic or biochemical) on at least 1 novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) for the treatment of metastatic CRPC, irrespective of prior NHT treatment for non castrate prostate cancer or nonmetastatic (M0) CRPC.

4. Bisphosphonate or denosumab dosage must have been stable for at least 4 weeks before day 1 for patients receiving these therapies.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

6. Estimated life expectancy of ≥ 6 months as assessed by the investigator.

7. Able to swallow the study drug, have no known intolerance to study drugs or excipients, and comply with study requirements.

8. Must use a condom when having sex from the time of the first dose of study drug through 4 months after last dose of study drug. A highly effective form of contraception must be used from the time of the first dose of study drug through 4 months after last dose of study drug when having sex with a non pregnant female partner of childbearing potential.

9. Must agree not to donate sperm from the first dose of study drug to 4 months after the last dose of study drug.

10. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

1. 1. Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist) or any other investigational agent within 4 weeks before day 1.

2. Prior treatment with a PARP inhibitor, cyclophosphamide, or mitoxantrone chemotherapy. Patients who discontinued prior platinum based chemotherapy <=6 months prior to screening or whose disease previously progressed on platinum based therapy at any time in the past are also excluded.

3. Treatment with any concurrent cytotoxic chemotherapy or investigational drug(s) within 4 weeks or 5 half lives of the drug (whichever is longer) before Day 1 and/or during study participation

4. Radiation therapy within 3 weeks (within 2 weeks, if single fraction of radiotherapy) before day 1.

5. Major surgery within 2 weeks before day 1.

6. Clinically significant cardiovascular disease.

7. Significant renal, hepatic, or bone marrow organ dysfunction.

8. Known or suspected brain metastasis or active leptomeningeal disease.

9. Symptomatic or impending spinal cord compression or cauda equina syndrome.

10. Prior diagnosis of myelodysplastic syndrome or acute myeloid leukemia

11. History of another cancer within 3 years before enrollment with the exception of nonmelanoma skin cancers, or American Joint Committee on Cancer stage 0 or stage 1 cancer that has a remote probability of recurrence in the opinion of the investigator and the sponsor.

12. Gastrointestinal disorder affecting absorption.

13. Current or anticipated use within 7 days prior to first dose of study drug or anticipated use during the study of the following P gp inhibitors (amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, verapamil, and valspodar).

14. Any other acute or chronic medical or psychiatric condition (concurrent disease, infection, or comorbidity) that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of data, in the opinion of the investigator or sponsor, including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

15. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.

16. Fertile male subjects who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 4 months after the last dose of investigational product.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates	Tempe	Arizona	United States	85284
2	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California	United States	91010
3	City of Hope-Antelope Valley	Lancaster	California	United States	93534
4	UC Irvine Health Investigational Drug Pharmacy	Orange	California	United States	92868
5	University of California, Irvine Medical Center	Orange	California	United States	92868
6	Medical Oncology Associates-SD	San Diego	California	United States	92123
7	Sharp Outpatient Infusion Therapy Center	San Diego	California	United States	92123
8	Sharp Rees-Stealy	San Diego	California	United States	92123
9	Emory University Hospital	Atlanta	Georgia	United States	30322
10	The Emory Clinic	Atlanta	Georgia	United States	30322
11	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
12	Piedmont Cancer Institute, PC	Fayetteville	Georgia	United States	30214
13	Piedmont Cancer Institute, PC	Newnan	Georgia	United States	30265
14	Siteman Cancer Center - West County	Creve Coeur	Missouri	United States	63141
15	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
16	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
17	Siteman Cancer Center - South County	Saint Louis	Missouri	United States	63129
18	Christian Hospital North East	Saint Louis	Missouri	United States	63136
19	Siteman Cancer Center - St. Peters	Saint Peters	Missouri	United States	63376
20	Weill Cornell Medical Center - New York Presbyterian Hospital	New York	New York	United States	10021
21	Weill Cornell Medical Center-New York Presbyterian Hospital	New York	New York	United States	10021
22	Levine Cancer Institute-Albermarle	Albemarle	North Carolina	United States	28001
23	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
24	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
25	Levine Cancer Institute-Pineville	Charlotte	North Carolina	United States	28210
26	Levine Cancer Institute-Southpark	Charlotte	North Carolina	United States	28211
27	Levine Cancer Institute-University	Charlotte	North Carolina	United States	28262
28	Levine Cancer Institute-Ballantyne	Charlotte	North Carolina	United States	28277
29	Levine Cancer Institute- Gaston	Gastonia	North Carolina	United States	28054
30	Levine Cancer Institute-Lincolnton	Lincolnton	North Carolina	United States	28092
31	Levine Cancer Institute-Monroe	Monroe	North Carolina	United States	28112
32	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
33	Parkway Surgery Center	Myrtle Beach	South Carolina	United States	29572
34	Levine Cancer Institute-Rock Hill	Rock Hill	South Carolina	United States	29732
35	The University of Texas Health Science Center at Tyler dba UT Health East Texas HOPE Cancer Center	Tyler	Texas	United States	75701
36	Virginia Oncology Associates	Hampton	Virginia	United States	23666
37	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
38	Swedish Cancer Institute Edmonds Campus	Edmonds	Washington	United States	98026
39	Swedish Cancer Institute Issaquah Campus	Issaquah	Washington	United States	98029
40	Swedish Cancer Institute	Seattle	Washington	United States	98104
41	Swedish Medical Center	Seattle	Washington	United States	98122
42	Froedtert Hospital/Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
43	Medical Imaging St Vincent's Hospital Sydney	Darlinghurst	New South Wales	Australia	2010
44	St Vincent's Hospital Sydney, The Kinghorn Cancer Centre	Darlinghurst	New South Wales	Australia	2010
45	PRP Diagnostic Imaging	Westmead	New South Wales	Australia	2145
46	Westmead Hospital	Westmead	New South Wales	Australia	2145
47	Icon Cancer Care Wesley	Auchenflower	Queensland	Australia	4066
48	Liz Plummer Cancer Care Center	Cairns	Queensland	Australia	4870
49	Icon Cancer Care Chermside	Chermside	Queensland	Australia	4032
50	Icon Cancer Care South Brisbane	South Brisbane	Queensland	Australia	4101
51	Icon Cancer Care	South Brisbane	Queensland	Australia	4101
52	Intergrated Clinical Oncology Network (ICON)	South Brisbane	Queensland	Australia	4101
53	Icon Cancer Care Southport	Southport	Queensland	Australia	4215
54	Eastern Clinical Research Unit	Box Hill	Victoria	Australia	3128
55	Eastern Health Pathology Service	Box Hill	Victoria	Australia	3128
56	Monash Medical Centre	Clayton	Victoria	Australia	3168
57	Peninsula Health	Frankston	Victoria	Australia	3199
58	Olivia Newton John Cancer Wellness & Research Centre Austin Health	Heidelberg	Victoria	Australia	3084
59	Ordensklinikum Linz, Barmherzige Schwestern	Linz	Upper Austria	Austria	4010
60	Vinzenz Pathologieverbund	Linz	Upper Austria	Austria	4010
61	Ordensklinikum Linz GmbH, Elisabethinen	Linz	Upper Austria	Austria	4020
62	Paracelsus Medical University, SALK	Salzburg		Austria	5020
63	Isotopix-Ambulatorium fur Nuklearmedizin	Vienna		Austria	1090
64	Medical University of Vienna	Vienna		Austria	1090
65	Medizinische Universitat Wien	Vienna		Austria	1090
66	Diagnosezentrum Meidling	Vienna		Austria	1120
67	Cliniques Universitaires Saint-Luc	Bruxelles		Belgium	1200
68	Algemeen Ziekenhuis Sint-Lucas	Gent		Belgium	9000
69	UZ Leuven, Campus Gasthuisberg	Leuven		Belgium	3000
70	Hospital de Caridade de Ijui	Ijui	RIO Grande DO SUL	Brazil	98700-000
71	Hospital de Clinicas de Porto Alegre-HCPA	Porto Alegre	RS	Brazil	90035-903
72	Fundacao Pio XII-Hospital de Cancer de Barretos	Barretos	SAO Paulo	Brazil	14784-400
73	Fundacao Doutor Amaral Carvalho	Jau	SAO Paulo	Brazil	17210-120
74	ICO-Site Paul Papin	Angers Cedex 02		France	49055
75	CHRUBesangon-H6pital Jean Minjoz	Besancon		France	25030
76	Institut Bergonie, Service d'Oncologie	Bordeaux cedex		France	33076
77	Centre Hospitalier Departemental Les Oudairies	La Roche sur Yon		France	85925
78	Clinique Victor Hugo-Centre Jean Bernard	Le Mans Cedex 02		France	72015
79	Institut de Cancerologie Strasbourg Europe	Strasbourg		France	67200
80	Hopital Foch Service Oncologie	Suresnes Cedex		France	92151
81	Institut Gustave Roussy	VILLEJUIF cedex		France	94805
82	Universitaetsklinikum Essen	Essen		Germany	45122
83	Medizinische Hochschule Hannover	Hannover		Germany	30625
84	Medizinische Fakultat Mannheim der Universitat Heidelberg	Mannheim		Germany	68167
85	Universitatsklinikum Munster	Munster		Germany	48149
86	Studienpraxis Urologie	Nuertingen		Germany	72622
87	Universitatsklinikum Tubingen	Tubingen		Germany	72076
88	Universitaetsklinikum Wuerzburg	Wuerzburg		Germany	97080
89	Semmelweis Egyetem	Budapest		Hungary	1082
90	Orszagos Onkologiai Intezet, "C" Belgyogyaszati-Onkologiai es Klinikai Farmakogogiai Osztaly	Budapest		Hungary	1122
91	Debreceni Egyetem	Debrecen		Hungary	4032
92	Szabolcs- Szatmar-Bereg Megyei Korhazak es Egyetemi Oktato Korhaz	Nyiregyhaza		Hungary	4400
93	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori	Meldola	Forli - Cesena	Italy	47014
94	Azienda Ospedaliera San Camillo Forlanini	Roma	Rome	Italy	00152
95	Azienda Ospedaliero-Universitaria S. Luigi Gonzaga-SCDU Oncologia Medica	Orbassano	Torino/piemonte	Italy	10043
96	AULSS3 Serenissima - Ospedale dell'Angelo - Oncologia Medica	Mestre	Venezia	Italy	30174
97	Azienda Socio Sanitaria Territoriale di Cremona (Istituti Ospitalieri di Cremona)	Cremona		Italy	26100
98	SD Oncologia Clinica Sperimentale di Uro-Ginecologia	Napoli		Italy	80131
99	IOV - Istituto Oncologico Veneto IRCCS - U.O. Oncologia Medica 1	Padova		Italy	35128
100	Azienda Ospedaliero Universitari di Parma - U.O. Oncologia Medica	Parma		Italy	43126
101	Azienda Ospedaliero Universitaria di Parma - U.O. Oncologia Medica	Parma		Italy	43126
102	Azienda Ospedaliero Universitaria Citta della Salute e della Scienza di Torino	Torino		Italy	10126
103	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
104	Pusan National University Hospital	Busan		Korea, Republic of	49241
105	Kyungpook National University Chilgok Hospital	Daegu		Korea, Republic of	41404
106	Severance Hospital, Yonsei University Health System	Seoul		Korea, Republic of	03722
107	Asan Medical Center	Seoul		Korea, Republic of	05505
108	Radboud UMC	Nijmegen	THE Netherlands	Netherlands	6525 GA
109	Szpital Specjalistyczny W Brzozowie, Podkarpacki Osrodek Onkologiczny Im.Ks.B.Markiewicza	Brzozow		Poland	36-200
110	Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej	Kielce		Poland	25-734
111	Hospital Virgen de la Victoria	Malaga	Malga	Spain	29010
112	Clinica Universidad de Navarra-Oncology Service	Pamplona	Navarra	Spain	31008
113	Hospital General Vall D'Hebron-Oncology Service	Barcelona		Spain	08035
114	Hospital Clinic de Barcelona	Barcelona		Spain	08036
115	Hospital Universitario Quironsalud Madrid-Oncology Service	Madrid		Spain	28223
116	Instituto Valenciano de Oncologia (IVO-FINCIVO)	Valencia		Spain	46009
117	Hospital Universitari i Politecnic La Fe	Valencia		Spain	46026
118	Mount Vernon Hospital	Northwood	Middlesex	United Kingdom	HA6 2RN
119	The Institute of Cancer Research, The Royal Marsden NHS Foundation Trust , Sycamore House	Sutton	Surrey	United Kingdom	SM2 5PT
120	Addenbrookes Hospital	Cambridge		United Kingdom	CB2 0QQ

Sponsors and Collaborators

• Pfizer
• Medivation, Inc.

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Nov 15, 2018
• Statistical Analysis Plan - Oct 1, 2020

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT03148795
• Other Study ID Numbers: MDV3800-06; C3441006; 2016-002036-32
• First Posted: May 11, 2017
• Last Update Posted: Aug 5, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Prostatic Neoplasms; Talazoparib

Study Results

Participant Flow

Recruitment Details

Participants with measurable soft tissue disease as per response evaluation criteria in solid tumors (RECIST) 1.1 and progressive metastatic castration-resistant prostate cancer (CRPC) and deoxyribonucleic acid (DNA) damage repair deficiencies, who previously received 1 to 2 taxane-based chemotherapy, and progressed on at least 1 line of novel hormonal therapy (enzalutamide and/or abiraterone acetate/prednisone) were enrolled.

Pre-assignment Detail

Currently results are reported for primary completion date (PCD), 04-Sep-2020.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 milligram per day (mg/day) orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Period Title: Overall Study
STARTED	128
Treated	127
COMPLETED	0
NOT COMPLETED	128

Baseline Characteristics

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Overall Participants	127
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.16 (8.02)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	127 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 3.1%
Not Hispanic or Latino	106 83.5%
Unknown or Not Reported	17 13.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 2.4%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 3.1%
White	110 86.6%
More than one race	0 0%
Unknown or Not Reported	10 7.9%

Outcome Measures

1. Primary Outcome

Title	Best Objective Response Rate (ORR)
Description	Best ORR was defined as the percentage of participants with best overall soft tissue response of complete response (CR) or partial response (PR) as per RECIST1.1 by an independent central review. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 millimeter (mm). Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 percent (%) decrease in sum of diameters of target lesions taking as reference baseline sum diameters.
Time Frame	From first dose of study drug to best overall soft tissue response CR or PR (maximum duration of 25 months)

Outcome Measure Data

Analysis Population Description

DDR deficient measurable disease population included all enrolled participants who had measurable soft tissue disease at screening by investigator assessment, had DDR deficiencies likely to sensitize to PARP inhibitor therapy, and received at least 1 dose of talazoparib.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	104
Number (95% Confidence Interval) [Percentage of participants]	29.8 23.5%

2. Secondary Outcome

Title	Time to Objective Response
Description	Time to objective response was defined as the time from first dose of talazoparib to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per prostate cancer working Group 3 (PCWG3). Soft tissue response is defined as a best overall response of CR or PR per RECIST 1.1 by independent central review. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 % decrease in sum of diameters of target lesions taking as reference baseline sum diameters.
Time Frame	From first dose of study drug to first objective response (maximum duration of 25 months)

Outcome Measure Data

Analysis Population Description

DDR deficient measurable disease population included all enrolled participants who had measurable soft tissue disease at screening by investigator assessment, had DDR deficiencies likely to sensitize to PARP inhibitor therapy, and received at least 1 dose of talazoparib and participants who achieved a confirmed CR or PR without documentation of confirmed bone progression.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	31
Median (Full Range) [Months]	3.4

3. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR was defined as the time from the first objective evidence of soft tissue response (CR or PR, whichever is earlier) per RECIST 1.1 and no evidence of confirmed bone disease progression per PCWG3 to the date of first objective evidence of radiographic progression or death due to any cause without evidence of radiographic progression, whichever occurs first. RECIST 1.1 criteria, CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than 10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (less than 10 mm short axis); PR: at least 30 % decrease in sum of diameters of target lesions taking as reference baseline sum diameters.
Time Frame	From the first objective evidence of soft tissue response (CR or PR, whichever is earlier) to radiographic progression or death due to any cause without evidence of radiographic progression, whichever occurs first (maximum duration of 25 months)

Outcome Measure Data

Analysis Population Description

DDR deficient measurable disease population included all enrolled participants who had measurable soft tissue disease at screening by investigator assessment, had DDR deficiencies likely to sensitize to PARP inhibitor therapy, and received at least 1 dose of talazoparib and participants who achieved a confirmed CR or PR without documentation of confirmed bone progression.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	31
Median (95% Confidence Interval) [Months]	12.8

4. Secondary Outcome

Title	Percentage of Participants With Prostate-Specific Antigen (PSA) Response of Greater Than or Equal to (>=) 50 Percent (%)
Description	Analysis is not final for this outcome measure at PCD, complete data will be posted at study completion date (SCD).
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Percentage of Participants With Circulating Tumor Cell (CTC) Count Greater Than or Equal to (>=) 5 Circulating Tumor Cell (CTC) Per 7.5 Milliliter (mL) of Blood at Baseline Decreasing to Less Than (<) 5 CTC of Blood Any Time on Study
Description	Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Percentage of Participants With Circulating Tumor Cell (CTC) Count >=1 CTC Per 7.5 mL of Blood at Baseline Decreasing to Null CTC of Blood Any Time on Study
Description	Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Percentage of Participants With Circulating Tumor Cell (CTC) Count <5 CTC Per 7.5 mL of Blood at Baseline Increased Any Time on Study
Description	Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Time to Prostate-Specific Antigen (PSA) Progression
Description	Time to PSA progression was defined as the time from first dose of study treatment to the date of PSA progression, which was subsequently confirmed. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Radiographic Progression-Free Survival (PFS)
Description	Radiographic PFS was defined as the time from date of first dose of talazoparib to first objective evidence of radiographic progression as assessed in soft tissue per modified RECIST 1.1 or confirmed progression in bone per PCWG3 guidelines by independent central review or death without documented radiographic progression, whichever occurs first.
Time Frame	From date of first dose of study drug to first objective evidence of radiographic progression or death without documented radiographic progression, whichever occurs first (maximum duration of 25 months)

Outcome Measure Data

Analysis Population Description

DDR deficient measurable disease population included all enrolled participants who had measurable soft tissue disease at screening by investigator assessment, had DDR deficiencies likely to sensitize to PARP inhibitor therapy, and received at least 1 dose of talazoparib.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	104
Median (95% Confidence Interval) [Months]	5.6

10. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the first dose of study treatment to death due to any cause. For participants who were alive, OS was censored at the last contact. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Time Frame	Baseline up to 28 days after last dose of study drug (approximately up to 26 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib including participants enrolled prior to amendment 3 with non-measurable disease and/or with DDR deficiencies, which may sensitize the tumor to PARP inhibition as assessed using an expanded DDR gene panel.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	127
Count of Participants [Participants]	121 95.3%

12. Secondary Outcome

Title	Number of Participants With Permanent Treatment Discontinuation Due to Adverse Events
Description	Treatment discontinuation was defined as permanent cessation of study drug treatment administration.
Time Frame	Baseline up to 28 days after last dose of study drug (approximately up to 26 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib including participants enrolled prior to amendment 3 with non-measurable disease and/or with DDR deficiencies, which may sensitize the tumor to PARP inhibition as assessed using an expanded DDR gene panel.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	127
Count of Participants [Participants]	15 11.8%

13. Secondary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Vital Signs
Description	Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): absolute result greater than (>) 180 mmHg and increase from baseline greater than or equal to (>=) 40 mmHg or absolute result < 90 mmHg and decrease from baseline > 30 mmHg; 2) Diastolic blood pressure (DBP) (mmHg): absolute result > 110 mmHg and increase from baseline >= 30 mmHg or absolute result < 50 mmHg and decrease from baseline > 20 mmHg or >= 20 mmHg increase from baseline; 3) Heart rate in beats per minutes (bpm): absolute result < 50 bpm and decrease from baseline > 20 bpm or absolute result > 120 bpm and increase from baseline > 30 bpm; Weight in kilogram: > 10% decrease from baseline.
Time Frame	Baseline up to 28 days after last dose of study drug (approximately up to 26 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib including participants enrolled prior to amendment 3 with non-measurable disease and/or with DDR deficiencies, which may sensitize the tumor to PARP inhibition as assessed using an expanded DDR gene panel. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies those participants who were evaluable at specified rows.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	125
SBP: Absolute result > 180 mm Hg and increase from baseline >= 40 mm Hg	0 0%
SBP: Absolute result < 90 mm Hg and decrease from baseline > 30 mm Hg	0 0%
DBP: Absolute result > 110 mm Hg and increase from baseline >= 30 mm Hg	0 0%
DBP: Absolute result < 50 mm Hg and decrease from baseline > 20 mm Hg	0 0%
DBP: >= 20 mm Hg increase from baseline	15 11.8%
Heart rate: Absolute result < 50 bpm and decrease from baseline > 20 bpm	0 0%
Heart rate: Absolute result > 120 bpm and increase from baseline > 30 bpm	1 0.8%
Weight: > 10% decrease from baseline	0 0%

14. Secondary Outcome

Title	Number of Participants With Shift in Laboratory Parameter Values (Hematology) From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline
Description	Hematology parameters included anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Severity was graded as Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE.
Time Frame	Baseline up to 28 days after last dose of study drug (approximately up to 26 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib including participants enrolled prior to amendment 3 with non-measurable disease and/or with DDR deficiencies, which may sensitize the tumor to PARP inhibition as assessed using an expanded DDR gene panel. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	124
Anemia	24 18.9%
Hemoglobin increased	0 0%
Lymphocyte count decreased	20 15.7%
Lymphocyte count increased	0 0%
Neutrophil count decreased	9 7.1%
Platelet count decreased	3 2.4%
White blood cell decreased	4 3.1%

15. Secondary Outcome

Title	Number of Participants With Shift in Laboratory Parameter Values (Chemistry) From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline
Description	Chemistry parameters:alanine aminotransferase increased(inc), alkaline phosphatase inc, aspartate aminotransferase inc, blood bilirubin inc, chronic kidney disease, creatinine inc, gamma-glutamyl transferase (GGT) inc, hypercalcemia, hypercalcemia, hyperkalemia, hypermagnesemia, hypermagnesemia, hypermagnesemia, hypocalcemia, hypocalcemia, hypokalemia, hypomagnesemia, hypophosphatemia and hypophosphatemia. Severity was graded as G1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; G2:moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental ADL; G3:severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G4:life-threatening consequence, urgent intervention indicated; G5: death related to AEs.
Time Frame	Baseline up to 28 days after last dose of study drug (approximately up to 26 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib including participants enrolled prior to amendment 3 with non-measurable disease and/or with DDR deficiencies, which may sensitize the tumor to PARP inhibition as assessed using an expanded DDR gene panel. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "number analyzed" signifies participants evaluable at specific rows.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	125
Alanine aminotransferase increased	0 0%
Alkaline phosphatase increased	9 7.1%
Aspartate aminotransferase increased	0 0%
Blood bilirubin increased	0 0%
Chronic kidney disease	1 0.8%
Creatinine increased	0 0%
GGT increased	3 2.4%
Hypercalcemia	0 0%
Hyperglycemia	3 2.4%
Hyperkalemia	4 3.1%
Hypermagnesemia	2 1.6%
Hypernatremia	0 0%
Hypoalbuminemia	0 0%
Hypocalcemia	3 2.4%
Hypoglycemia	0 0%
Hypokalemia	0 0%
Hypomagnesemia	1 0.8%
Hyponatremia	3 2.4%
Hypophosphatemia	2 1.6%

16. Secondary Outcome

Title	Number of Participants With Dose Modification
Description	Number of participants with dose modification due to adverse events was reported.
Time Frame	Baseline up to 28 days after last dose of study drug (approximately up to 26 months)

Outcome Measure Data

Analysis Population Description

Safety population included all participants who received at least 1 dose of talazoparib including participants enrolled prior to amendment 3 with non-measurable disease and/or with DDR deficiencies, which may sensitize the tumor to PARP inhibition as assessed using an expanded DDR gene panel.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	127
Count of Participants [Participants]	33 26%

17. Secondary Outcome

Title	Time to Deterioration in Pain Symptom Scores
Description	Time to deterioration in pain symptom scores was assessed by brief pain inventory short form (BPI-SF). Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Secondary Outcome

Title	Change From Baseline in Participant Reported Pain Scores Per BPI-SF Till End of the Study
Description	BPI-SF is an 11-item self-report questionnaire that is designed to assess the severity and impact of pain on daily functions. BPI-SF are 4 questions that assess pain intensity (worst, least, average, right now) and 7 questions that assess impact of pain on daily functions (general activity, mood, walking ability, normal work, relations with other people, sleep, enjoyment of life). Each question is answered on a scale ranging from 0 to 10; '0=No pain and 10=Pain as bad as you can imagine'. Measure can be scored by item, with lower scores being indicative of less pain or pain interference. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Secondary Outcome

Title	Change From Baseline in Patient-Reported Health-Related Quality of Life as Assessed by European Quality of Life 5-Domain 5-Level Scale (EQ-5D-5L) Scores Till End of the Study
Description	The EQ-5D-5L consists of two sections, the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS).The EQ-5D descriptive system comprises the following five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression with five response levels for each dimension: no problems, slight problems, moderate problems, severe problems and extreme problems. The EQ-5D VAS is a 20 cm vertical scale where patients can mark from 0 (worst health imaginable) to 100 (best health imaginable). Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction. Analysis is not final for this outcome measure at PCD, complete data will be posted at SCD.
Time Frame	Approximately 56 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Secondary Outcome

Title	Pre-dose Plasma Concentration (Ctrough) of Talazoparib
Description	Ctrough was defined as pre-dose plasma concentration during dosing and observed directly from data.
Time Frame	Pre-dose at Week 1, 5, 9 and 13

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population included all participants from the safety population who had at least 1 reportable drug concentration data point. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable at specified time points.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	92
At Week 1	2631.898 (23.2043)
At Week 5	4748.147 (63.2488)
At Week 9	4213.250 (52.8028)
At Week 13	4378.123 (47.5360)

21. Secondary Outcome

Title	Post-dose Plasma Concentration (Ctrough) of Talazoparib
Description	Plasma concentration was measured 2 hours after dosing and observed directly from data.
Time Frame	2 hours post-dose at Week 1 and 5

Outcome Measure Data

Analysis Population Description

PK population included all participants from the safety population who had at least 1 reportable drug concentration data point. Here, "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and "Number Analyzed" signifies participants evaluable at specified time points.

Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
Measure Participants	31
At week 1	2289.540 (51.0724)
At Week 5	10713.918 (49.4248)

Adverse Events

Time Frame	Baseline up to 28 days after last dose of study drug (maximum up to 26 months)
Adverse Event Reporting Description	Same event may appear as both an AE and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety population set was analyzed.
Arm/Group Title	Talazoparib
Arm/Group Description	Participants received talazoparib 1 mg/day orally until radiographic progression that was determined by independent central review, unacceptable toxicity, withdrawal of consent, or death. Talazoparib was continued upon disease progression only if, in the opinion of the investigator the participant was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was 25 months.
All Cause Mortality
	Talazoparib
	Affected / at Risk (%)	# Events
Total	11/127 (8.7%)
Serious Adverse Events
	Talazoparib
	Affected / at Risk (%)	# Events
Total	43/127 (33.9%)
Blood and lymphatic system disorders
Anemia	5/127 (3.9%)
Cardiac disorders
Cardio-respiratory arrest	1/127 (0.8%)
Gastrointestinal disorders
Abdominal pain	1/127 (0.8%)
Constipation	1/127 (0.8%)
Rectal hemorrhage	1/127 (0.8%)
Vomiting	1/127 (0.8%)
General disorders
Asthenia	1/127 (0.8%)
Disease progression	4/127 (3.1%)
General physical health deterioration	2/127 (1.6%)
Pain	2/127 (1.6%)
Pyrexia	2/127 (1.6%)
Infections and infestations
Bronchitis	1/127 (0.8%)
Parotitis	1/127 (0.8%)
Pneumonia	3/127 (2.4%)
Sepsis	1/127 (0.8%)
Urinary tract infection	3/127 (2.4%)
Injury, poisoning and procedural complications
Fall	1/127 (0.8%)
Overdose	1/127 (0.8%)
Subdural hematoma	2/127 (1.6%)
Investigations
Platelet count decreased	2/127 (1.6%)
SARS-CoV-2 test positive	1/127 (0.8%)
White blood cell count decreased	1/127 (0.8%)
Musculoskeletal and connective tissue disorders
Back pain	1/127 (0.8%)
Bursitis	1/127 (0.8%)
Pain in extremity	1/127 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/127 (0.8%)
Malignant neoplasm progression	1/127 (0.8%)
Neoplasm progression	1/127 (0.8%)
Pancreatic carcinoma	1/127 (0.8%)
Nervous system disorders
Hemianopia	1/127 (0.8%)
Paresthesia	1/127 (0.8%)
Renal and urinary disorders
Dysuria	1/127 (0.8%)
Hematuria	1/127 (0.8%)
Nephrolithiasis	1/127 (0.8%)
Reproductive system and breast disorders
Penile pain	1/127 (0.8%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/127 (0.8%)
Dyspnea	1/127 (0.8%)
Pneumonia aspiration	1/127 (0.8%)
Pulmonary embolism	8/127 (6.3%)
Vascular disorders
Hypotension	1/127 (0.8%)
Other (Not Including Serious) Adverse Events
	Talazoparib
	Affected / at Risk (%)	# Events
Total	120/127 (94.5%)
Blood and lymphatic system disorders
Anemia	61/127 (48%)
Gastrointestinal disorders
Constipation	23/127 (18.1%)
Diarrhea	21/127 (16.5%)
Nausea	42/127 (33.1%)
Vomiting	16/127 (12.6%)
General disorders
Asthenia	30/127 (23.6%)
Fatigue	25/127 (19.7%)
Edema peripheral	21/127 (16.5%)
Pyrexia	10/127 (7.9%)
Infections and infestations
Upper respiratory tract infection	8/127 (6.3%)
Urinary tract infection	7/127 (5.5%)
Injury, poisoning and procedural complications
Fall	8/127 (6.3%)
Investigations
Alanine aminotransferase increased	7/127 (5.5%)
Aspartate aminotransferase increased	8/127 (6.3%)
Lymphocyte count decreased	10/127 (7.9%)
Neutrophil count decreased	21/127 (16.5%)
Platelet count decreased	24/127 (18.9%)
White blood cell count decreased	12/127 (9.4%)
Metabolism and nutrition disorders
Decreased appetite	36/127 (28.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/127 (7.9%)
Back pain	16/127 (12.6%)
Bone pain	9/127 (7.1%)
Musculoskeletal pain	9/127 (7.1%)
Pain in extremity	12/127 (9.4%)
Nervous system disorders
Dizziness	15/127 (11.8%)
Headache	9/127 (7.1%)
Paresthesia	8/127 (6.3%)
Psychiatric disorders
Insomnia	8/127 (6.3%)
Renal and urinary disorders
Hematuria	8/127 (6.3%)
Respiratory, thoracic and mediastinal disorders
Cough	9/127 (7.1%)
Dyspnea	16/127 (12.6%)
Vascular disorders
Hot flush	10/127 (7.9%)
Hypertension	7/127 (5.5%)

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.