Clinical Trial Results:
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)
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Summary
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EudraCT number |
2016-002036-32 |
Trial protocol |
DE NL ES FR BE GB AT DK HU IT |
Global end of trial date |
31 Mar 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Mar 2024
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First version publication date |
23 Mar 2024
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C3441006
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03148795 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
MDV3800-06: Other ID | ||
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Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, NY 10017
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Public contact |
Pfizer Inc., Pfizer ClinicalTrials.gov Call Center, 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Jul 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Mar 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy, of single agent talazoparib in Deoxyribonucleic acid damage repair (DDR) + Metastatic castration-resistant prostate cancer (mCRPC) as measured by best objective response rate (ORR).
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jul 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Australia: 11
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Country: Number of subjects enrolled |
Germany: 6
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Country: Number of subjects enrolled |
Brazil: 1
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Country: Number of subjects enrolled |
French Guiana: 22
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Country: Number of subjects enrolled |
Hungary: 3
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Country: Number of subjects enrolled |
Italy: 23
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Country: Number of subjects enrolled |
Belgium: 12
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Country: Number of subjects enrolled |
Spain: 5
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Country: Number of subjects enrolled |
Austria: 4
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Country: Number of subjects enrolled |
Netherlands: 15
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Country: Number of subjects enrolled |
Korea, Republic of: 1
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Country: Number of subjects enrolled |
Poland: 1
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Country: Number of subjects enrolled |
United Kingdom: 7
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Country: Number of subjects enrolled |
United States: 16
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Worldwide total number of subjects |
127
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EEA total number of subjects |
69
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
39
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From 65 to 84 years |
88
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
Subjects with measurable soft tissue disease as per RECIST 1.1 and progressive metastatic castration-resistant prostate cancer (CRPC) and DNA damage repair deficiencies, 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. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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Talazoparib | ||||||||||
Arm description |
Subjects 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 subject was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was approximately 36 months. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Talazoparib
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Investigational medicinal product code |
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Other name |
PF-06944076
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received talazoparib 1 milligram per day (mg/day).
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Baseline characteristics reporting groups
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Reporting group title |
Talazoparib
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Reporting group description |
Subjects 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 subject was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was approximately 36 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Talazoparib
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Reporting group description |
Subjects 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 subject was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was approximately 36 months. | ||
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End point title |
Best Objective Response Rate (ORR) [1] | ||||||||
End point description |
Best ORR was defined as the percentage of subjects 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. DDR deficient measurable disease population included all enrolled subjects 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.
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End point type |
Primary
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End point timeframe |
From first dose of study drug to best overall soft tissue response CR or PR (maximum duration of 25 months)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Prostate-Specific Antigen (PSA) Response of Greater Than or Equal to (>=) 50 Percentage (%) | ||||||||
End point description |
Percentage of subjects with PSA response of >= 50% was reported in this outcome measure. PSA response was calculated as a decline from baseline PSA (ng/mL) by at least 50% measured by central laboratory. Final analyses for this endpoint was till the cutoff date 04 September 2020. DDR deficient measurable disease population included all enrolled subjects 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. Here ‘’Number of subjects analyzed’’ signifies number of subjects evaluable data for this endpoint.
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End point type |
Secondary
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End point timeframe |
From the date of first dose of study treatment until confirmed PSA progression or start of new anticancer treatment given after the first dose of study treatment (maximum duration of 25 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DOR) | ||||||||
End point 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. DDR deficient measurable disease population evaluated. 99999 indicates Upper limit of 95% confidence interval (CI) was not estimable as there were less number of subjects with an event.
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End point type |
Secondary
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End point timeframe |
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)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With Conversion of Circulating Tumor Cell (CTC) Count | ||||||||
End point description |
Percentage of subjects with conversion of CTC count was defined as percentage of subjects with a CTC count >= 5 CTC per 7.5 milliliter (mL) of blood at baseline that decreased to < 5 CTC per 7.5 mL of blood any time on study. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects with a baseline CTC assessment and at least 1 post-baseline CTC assessment from the DDR deficient measurable disease population. Subjects with a CTC count <5 per 7.5 mL of blood at baseline were not analyzed for this conversion endpoint. Here, "Number of subjects analyzed’’ signifies number of subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to anytime on study during final analyses (maximum duration of 25 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Objective Response | ||||||||
End point 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. DDR deficient measurable disease population evaluated.
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End point type |
Secondary
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End point timeframe |
From first dose of study drug to first objective response (maximum duration of 25 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
: Percentage of Subjects With Baseline CTC Count <5 CTC Showed Increased CTC Counts at any Time on Study | ||||||||
End point description |
Percentage of subjects with CTC count <5 CTC per 7.5 mL of blood at baseline those who showed an increased CTC count, compared to baseline, any time on study was reported in this study. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects with a baseline CTC assessment and at least 1 post-baseline CTC assessment from the DDR deficient measurable disease population. Here, "Number of subjects analyzed’’ signifies number of subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to anytime on study during final analyses (maximum duration of 25 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Prostate-Specific Antigen (PSA) Progression | ||||||||
End point 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. The time from first dose of talazoparib to the date that a >=25% increase in PSA with an absolute increase of ≥2micogram per liter (2 nanogram per mL) above the nadir (or baseline for subjects with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained >=3 weeks (21 days) later. Kaplan-Meier method was used for analysis. Final analyses for this endpoint was till the cutoff date 04 September 2020. DDR deficient measurable disease population included all enrolled subjects 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.
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End point type |
Secondary
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End point timeframe |
From the date of first dose of study treatment until confirmed PSA progression or start of new anticancer treatment given after the first dose of study treatment (maximum duration of 25 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With a Null CTC Count | ||||||||
End point description |
Percentage of subjects with a null CTC count was defined as percentage of subjects with CTC count >=1 CTC per 7.5 mL of blood at baseline that decreased to CTC = 0 per 7.5 mL of blood any time on study. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects with a baseline CTC assessment and at least 1 post-baseline CTC assessment from the DDR deficient measurable disease population. Subjects with a CTC count 0 per 7.5 mL of blood at baseline were not analyzed for this endpoint. Here, "Number of subjects analyzed’’ signifies number of subjects evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline to anytime on study during final analyses (maximum duration of 25 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Radiographic Progression-Free Survival (PFS) | ||||||||
End point 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. DDR deficient measurable disease population included all enrolled subjects 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.
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End point type |
Secondary
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End point timeframe |
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)
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from start date (the date of first dose of treatment) to the date of death due to any cause. Subjects who had not died were censored at the date of last contact. Kaplan-Meier method was used for analysis. Final analyses for this endpoint was till the cutoff date 31 March 2023. DDR deficient measurable disease population included all enrolled subjects 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.
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End point type |
Secondary
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End point timeframe |
From first dose of study treatment up to death due to any cause during study or date of last contact (approximately 36 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Subjects With Treatment Emergent Adverse Events (TEAEs) | ||||||
End point description |
An adverse event (AE) was any untoward medical occurrence in a subjects who received study drug without regard to possibility of causal relationship. AEs included both serious AEs and all non-serious AEs. 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. Safety population included all subjects who received at least 1 dose of talazoparib including subjects 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.
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End point type |
Secondary
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End point timeframe |
First dose of study drug up to 28 days after last dose of study drug (study treatment was approximately for 36 months, safety follow up to approximately 37 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Permanent Treatment Discontinuation Due to Adverse Events | ||||||
End point description |
Treatment discontinuation was defined as permanent cessation of study drug treatment administration. Safety population included all subjects who received at least 1 dose of talazoparib including subjects 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.
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End point type |
Secondary
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End point timeframe |
During study treatment (approximately up to 36 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects With Clinically Significant Abnormalities in Vital Signs | ||||||||||||||||||||||
End point description |
Vital sign abnormalities criteria included: 1) Systolic blood pressure (SBP) in millimeters of mercury (mmHg): absolute result (AR) greater than (>) 180 mmHg and increase from baseline (IFB) greater than or equal to (>=) 40 mmHg or AR < 90 mmHg and decrease from baseline (DFB) > 30 mmHg; 2) Diastolic blood pressure (DBP) (mmHg): AR > 110 mmHg and IFB >= 30 mmHg or AR < 50 mmHg and DFB > 20 mmHg or >= 20 mmHg IFB; 3) Heart rate in beats per minutes (bpm): AR < 50 bpm and DFB > 20 bpm or AR > 120 bpm and IFB > 30 bpm; Weight in kilogram: > 10% DFB. Safety population evaluated. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this endpoint and "n” signifies those subjects who were evaluable at specified rows.
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End point type |
Secondary
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End point timeframe |
During study treatment (approximately up to 36 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of Subjects With Shift in Laboratory Parameter Values (Hematology) From Grade less than equal to (<=) 2 at Baseline to Grade 3 or 4 Post-baseline | ||||||||||||||||||||||
End point description |
Hematology parameters included anemia, hemoglobin increased, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased, Leukocytosis 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 non-invasive 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. Safety population evaluated. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this endpoint. “n” signifies subjects evaluable at specific rows.
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End point type |
Secondary
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End point timeframe |
During study treatment (approximately up to 36 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Number of Subjects With Shift in Laboratory Parameter Values (Chemistry) From Grade <=2 at Baseline to Grade 3 or 4 Post-baseline | ||||||||||||||||||||||||||||||||||||||||||||
End point description |
Parameters: alanine aminotransferase (AT) increased (inc), alkaline phosphatase inc, aspartate AT inc, blood bilirubin inc, chronic kidney disease, creatinine inc, gamma-glutamyl transferase (GGT) inc, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypocalcemia, hyponatremia, hypoglycemia, hypokalemia, hypomagnesemia, hypernatremia, hypoalbuminemia, hypophosphatemia. Grade(G)1: 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. Safety set used. “Number of Subjects Analyzed”: subjects evaluable for endpoint; “n”: subjects evaluable at specific rows.
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End point type |
Secondary
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End point timeframe |
During study treatment (approximately up to 36 months)
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With Dose Modification | ||||||
End point description |
Number of subjects with dose modification due to adverse events was reported. Safety population included all subjects who received at least 1 dose of talazoparib including subjects 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.
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End point type |
Secondary
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End point timeframe |
During study treatment (approximately up to 36 months)
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| No statistical analyses for this end point | |||||||
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End point title |
Time to Deterioration in Pain Symptom Scores | ||||||||
End point description |
Time deterioration is based on BPI-SF question 3: “Please rate your pain by marking the box beside the number that best describes your pain at its worst in the last 24 hours.” Pain intensity was to be answered on a range of 0 to 10, where 0 corresponded to no pain and 10 worst pain. Time to this event is defined as the time from the date of first dose of study treatment to onset of pain progression, where pain progression is defined as a 2-point or more increase from baseline in the question 3 score. Kaplan-Meier method was used for analysis. Average of all assessments visits is reported in this endpoint. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects from the DDR deficient measurable disease population with a baseline PRO assessment and at least 1 post-baseline PRO assessment prior to the end of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline till final analysis (maximum duration of 25 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline in Subjects Reported Pain Scores per BPI-SF Question 3 Through Final Analysis | ||||||||||||||||||||||||||||||||||||||
End point description |
BPI-SF:11-item self-report questionnaire, assessed severity and impact of pain on daily functions. BPI-SF have 4 questions to assess pain intensity (worst, least, average, right now) and 7 questions to 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 from 0 (No pain) to 10 (Pain as bad as you can imagine). Measure can be scored by item, lower scores = less pain or pain interference. BPI-SF question 3 was related to subjects experiencing worst pain in last 24 hours, score range 0 to 10, large values = worse outcomes. Final analysis for this endpoint was till the cutoff date 04 September 2020. DDR deficient measurable disease population evaluated. All subjects reported under 'Number of Subjects Analyzed’ contributed data to the table; however, may not have evaluable data for every row. “n” signifies subjects evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 3, 5, 7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||
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End point title |
Change From Baseline in European Quality of Life 5-Domain 5-Level Scale (EQ-5D-5L) Visual Analogue Scores (VAS) | ||||||||||||||||||||||||||||||||||||||||
End point description |
The EQ-5D VAS score was a subjects rated questionnaire where subjects rated how they felt at assessment visit on a vertical VAS that ranged from 0 (worst imaginable health state) to 100 (best imaginable health state), with higher scores indicating a better health condition. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects from the DDR deficient measurable disease population with a baseline PRO assessment and at least 1 post-baseline PRO assessment prior to the end of treatment. All subjects reported under ‘Number of Subjects Analyzed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of subjects evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With 5 Response Levels for EQ-5D-5L Mobility Domain | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-5L: subjects rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D mobility domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects from the DDR deficient measurable disease population with a baseline PRO assessment and at least 1 post-baseline PRO assessment prior to the end of treatment. All subjects reported under ‘Number of Subjects Analyzed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of subjects evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With 5 Response Levels for EQ-5D-5L Self-Care Domain | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-5L: subjects rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D self-care domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects from the DDR deficient measurable disease population with a baseline PRO assessment and at least 1 post-baseline PRO assessment prior to the end of treatment. All subjects reported under ‘Number of Subjects Analyzed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of subjects evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With 5 Response Levels for EQ-5D-5L Usual Activity Domain | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-5L: subjects rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D usual activities domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects from the DDR deficient measurable disease population with a baseline PRO assessment and at least 1 post-baseline PRO assessment prior to the end of treatment. All subjects reported under ‘Number of Subjects Analyzed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of subjects evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With 5 Response Levels for EQ-5D-5L Pain and Discomfort Domain | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-5L: subjects rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D pain and discomfort domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects from the DDR deficient measurable disease population with a baseline PRO assessment and at least 1 post-baseline PRO assessment prior to the end of treatment. All subjects reported under ‘Number of Subjects Analyzed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of subjects evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects With 5 Response Levels for EQ-5D-5L Anxiety and Depression Domain | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
EQ-5D-5L: subjects rated assessed level of current health using 5 domains: mobility, self-care, usual activities, pain and discomfort, anxiety, and depression. EQ-5D anxiety and depression domain had 5 responses: no problem, slight problem, moderate problem, severe problem and extreme problem. Final analyses for this endpoint was till the cutoff date 04 September 2020. All subjects from the DDR deficient measurable disease population with a baseline PRO assessment and at least 1 post-baseline PRO assessment prior to the end of treatment. All subjects reported under ‘Number of Subjects Analyzed’ contributed data to the table; however, may not have evaluable data for every row. Here, “n” signifies number of subjects evaluable for specified time points.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 1, 3, 5,7, 9, 13, 17, 21, 25, 37, 49, 61, 73, 85, 97, Follow-up Visit (28 days after last dose) [maximum duration of 25 months]
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Pre-dose Plasma Concentration (Ctrough) of Talazoparib | ||||||||||||||||
End point description |
Ctrough was defined as pre-dose plasma concentration during dosing and observed directly from data. Pharmacokinetic (PK) population included all subjects from the safety population who had at least 1 reportable drug concentration data point. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this endpoint and "n” signifies subjects evaluable at specified time points.
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End point type |
Secondary
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End point timeframe |
Pre-dose at Week 1, 5, 9 and 13
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| No statistical analyses for this end point | |||||||||||||||||
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End point title |
Post-dose Plasma Concentration (Ctrough) of Talazoparib | ||||||||||||
End point description |
Plasma concentration was measured 2 hours after dosing and observed directly from data. PK population included all subjects from the safety population who had at least 1 reportable drug concentration data point. Here, “Number of Subjects Analyzed” signifies subjects evaluable for this endpoint and "n” signifies subjects evaluable at specified time points.
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End point type |
Secondary
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End point timeframe |
2 hours post-dose at Week 1 and 5
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
SAEs and Non-SAEs: Baseline up to 28 days after last dose of study drug (maximum up to 37 months); All-cause mortality: During study included safety follow up and beyond that (approximately 69 months of study)
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Adverse event reporting additional 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 subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event. Safety population set was analyzed.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
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Reporting groups
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Reporting group title |
Talazoparib
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Reporting group description |
Subjects 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 subjects was clinically benefitting, no new concurrent systemic therapy was initiated, and the sponsor was notified. Maximum duration of treatment was approximately 36 months. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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31 Mar 2017 |
Safety related updates included:
- Increased the frequency of clinical laboratory tests after week 25 from every 12 weeks to every 8 weeks for increased patient safety and consistency across talazoparib studies.
- Added guidance for dose modification of talazoparib and updates talazoparib product information for increased patient safety and consistency across talazoparib studies. |
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15 Nov 2018 |
The primary purpose of this Amendment is to address updated information reported in the August 2018 version of the Talazoparib Investigator’s Brochure. In addition, guidance for talazoparib dose modifications due to adverse events was updated to align with the Risk Management Committee (RMC)
recommendations and the proposed regional labels. Changes included:
• Extension of the time required, for contraceptive use and for patients to refrain from sperm donation, from 105 days to
4 months.
• Clarification/changes regarding prior and concomitant medications.
• Clarifications to responses to adverse events, including talazoparib dose modifications.
• Updated safety and efficacy data from clinical studies in patients that have taken talazoparib.
• Updated pharmacokinetics data.
• Update to the benefits and risks assessment.
• The section pertaining to medication errors was updated to address talazoparib overdose. |
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22 Sep 2022 |
Safety related updates included: Talazoparib Benefits and Risks Assessment section was amended with updated information reported in the May 2021 version of the Talazoparib Investigator's Brochure. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
