Brief Summary

This study compares rPFS in men with mCRPC treated with talazoparib plus enzalutamide vs. enzalutamide after confirmation of the starting dose of talazoparib in combination with enzalutamide.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network

Enrollment

1,054

participants targeted

Target at P75+ for phase_3

Timeline

14mo left

Started Dec 2017

Longer than P75 for phase_3

Geographic Reach

26 countries

368 active sites

Status

active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

9.5 years study duration

Study Progress88%

Dec 2017Jun 2027

First Submitted

Initial submission to the registry

November 21, 2017

Completed

27 days until next milestone

Study Start

First participant enrolled

December 18, 2017

Completed

23 days until next milestone

First Posted

Study publicly available on registry

January 10, 2018

Completed

4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 3, 2022

Completed

1.3 years until next milestone

Results Posted

Study results publicly available

January 17, 2024

Completed

3.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 30, 2027

Expected

Last Updated

April 22, 2026

Status Verified

April 1, 2026

Enrollment Period

4.8 years

First QC Date

November 21, 2017

Results QC Date

September 21, 2023

Last Update Submit

April 20, 2026

Conditions

mCRPC

Keywords

mCRPC (metastatic castration-resistant prostate cancer)

Outcome Measures

Primary Outcomes (8)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1
An adverse event (AE) was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per Common Terminology Criteria for Adverse Events (CTCAE) version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. Serious TEAE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were determined according to the investigator's assessment. Results as of 16 Aug 2022 are reported.
Post dose on Day 1 up to Day 66 in Part 1
Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by Preferred Term (PT) and Max CTCAE Grade Occuring Within the First 66 Days of Dosing - Part 1
An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per CTCAE version 4, Grade 1=mild AE; Grade 2=moderate AE; Grade 3=severe AE; Grade 4=life-threatening or disabling AE; Grade 5=death related to an AE. Medical Dictionary for Regulatory Activities (MedDRA) v25.0 coding dictionary applied. PTs for the cluster terms are: ANEMIA, including Anemia, Hematocrit decreased, Hemoglobin decreased, and Red blood cell count decreased; THROMBOCYTOPENIA, including, Thrombocytopenia and Platelet count decreased; NEUTROPENIA, including Febrile neutropenia, Neutropenia and Neutrophil count decreased; LEUKOPENIA, including Leukopenia, White blood cell count decreased. Events in any grade with at least 1 occurrence in participants are reported for this outcome measure. Results as of 16 Aug 2022 are reported.
Post dose on Day 1 up to Day 66 in Part 1
Number of Participants With All-Causality TEAEs During the Overall Period of Part 1
An adverse event (AE) was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. Serious TEAE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were determined according to the investigator's assessment. Results as of 16 Aug 2022 are reported.
Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1
An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were determined according to the investigator's assessment. Results as of 16 Aug 2022 are reported.
Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1
An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are defined as newly occurring AEs or those worsening after first dose. As per CTCAE version 4, Grade 1=mild AE; Grade 2=moderate AE; Grade 3=severe AE; Grade 4=life-threatening or disabling AE; Grade 5=death related to an AE. MedDRA v25.0 coding dictionary applied. PTs for the cluster terms are: ANEMIA, including Anemia, Hematocrit decreased, Hemoglobin decreased, and Red blood cell count decreased; THROMBOCYTOPENIA, including, Thrombocytopenia and Platelet count decreased; NEUTROPENIA, including Febrile neutropenia, Neutropenia and Neutrophil count decreased; LEUKOPENIA, including Leukopenia, White blood cell count decreased. Events in any grade with at least 1 occurrence in participants are reported for this outcome measure. Results as of 16 Aug 2022 are reported.
Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Number of Participants With Treatment-Related Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade in >=10% of Participants Occuring Anytime After Dosing - Part 1
An AE was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. TEAEs are newly occurring AEs or those worsening after first dose. Treatment-related AE was any AE attributed to study intervention in a participant who received study intervention. As per CTCAE version 4, Grade 1=mild; Grade 2=moderate; Grade 3=severe; Grade 4=life-threatening or disabling; Grade 5=death related to an AE. MedDRA v25.0 coding dictionary applied. PTs for the cluster terms are: ANEMIA, including Anemia, Hematocrit decreased, Hemoglobin decreased, and Red blood cell count decreased; THROMBOCYTOPENIA, including, Thrombocytopenia and Platelet count decreased; NEUTROPENIA, including Febrile neutropenia, Neutropenia and Neutrophil count decreased; LEUKOPENIA, including Leukopenia, White blood cell count decreased. Events in any grade with incidence in \>=10% of participants are reported. Results as of 16 Aug 2022 are reported.
Post dose on Day 1 up to 28 days after the last dose of study intervention, or before new systemic antineoplastic therapy, whichever occurred first (maximum of 235.14 weeks)
Blinded Independent Central Review (BICR) Assessed Radiographic Progression-Free Survival (rPFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for All-Comers - Part 2 Cohort 1
rPFS is defined as the time from the date of randomization to first objective evidence of radiographic progression as assessed in soft tissue per RECIST 1.1, or death, whichever occurs first. Soft tissue disease status was assessed at regular intervals during the course of the study by computed tomography (CT) of chest and CT or magnetic resonance imaging (MRI) of abdomen and pelvis. Progression is defined using RECIST 1.1 as a \>=20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Results as of 16 Aug 2022 are reported for this outcome measure.
From the start of treatment to the time of first documented progression, or death (maximum up to 42 months)
BICR Assessed rPFS Per RECIST 1.1 in Patients With DDR Deficiencies - Part 2
rPFS is defined as the time from the date of randomization to first objective evidence of radiographic progression as assessed in soft tissue per RECIST 1.1, or death, whichever occurs first. Soft tissue disease status was assessed at regular intervals during the course of the study by CT of chest and CT or MRI of abdomen and pelvis. Results as of 03 Oct 2022 are reported for this outcome measure.
From the start of treatment to the time of first documented progression, or death (maximum up to 38 months)

Study Arms (2)

Combination arm

EXPERIMENTAL

Talazoparib plus enzalutamide

Drug: Talazoparib with enzalutamide

Monotherapy arm

ACTIVE COMPARATOR

Ezalutamide plus placebo

Drug: Placebo with enzalutamide

Interventions

Talazoparib with enzalutamideDRUG

Talazoparib 0.5 mg/day plus enzalutamide 160mg/day

Combination arm

Placebo with enzalutamideDRUG

Placebo plus enzalutamide 160 mg/day

Monotherapy arm

Eligibility Criteria

Age18 Years+

Sexmale(Gender-based eligibility)

Gender Eligibility DetailsMen at least 18 years of age. For Japan, at least 20 years of age.

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell or signet cell features
Asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) (score on BPI-SF Question #3 must be \< 4).
For enrollment into Part 2 only (optional in Part 1): assessment of DDR mutation status
Consent to a saliva sample collection for a germline comparator unless prohibited by local regulations or ethics committee decision (optional for patients in Part 1).
Surgically or medically castrated, with serum testosterone ≤ 50 ng/dL (≤ 1.73 nmol/L) at screening.
Metastatic disease in bone documented on bone scan or in soft tissue documented on CT/MRI scan.
Progressive disease at study entry in the setting of medical or surgical castration as defined by 1 or more of the following 3 criteria:
Prostate specific antigen (PSA) progression defined by a minimum of 2 rising PSA values from 3 consecutive assessments with an interval of at least 7 days between assessments..
Soft tissue disease progression as defined by RECIST 1.1.
Bone disease progression defined by Prostate Cancer Working Group 3 (PCWG3) with 2 or more new metastatic bone lesions on a whole body radionuclide bone scan.
Ongoing bisphosphonate or denosumab use prior to Day 1 (Part 1) or randomization (Part 2) is allowed but not mandatory.
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
Life expectancy ≥ 12 months as assessed by the investigator.
Able to swallow the study drug and have no known intolerance to study drugs or excipients.
Must agree to use a condom when having sex with a partner from the time of the first dose of study drug through 4 months after last dose of study treatment. Must also agree for female partner of childbearing potential to use an additional highly effective form of contraception from the time of the first dose of study treatment through 4 months after last dose of study treatment when having sex with a non pregnant female partner of childbearing potential.
+3 more criteria

You may not qualify if:

Any prior systemic cancer treatment initiated in in the non metastatic CRPC and mCRPC disease state.
Patients whose only evidence of metastasis is adenopathy below the aortic bifurcation.
Prior treatment with second-generation androgen receptor inhibitors (enzalutamide, apalutamide, and darolutamide), a PARP inhibitor, cyclophosphamide, or mitoxantrone for prostate cancer.
Prior treatment with platinum-based chemotherapy within 6 months (from the last dose) prior to Day 1 (Part 1) or randomization (Part 2), or any history of disease progression on platinum-based therapy within 6 months (from the last dose).
Treatment with any investigational agent within 4 weeks before Day 1 (Part 1) or randomization (Part 2).
Prior treatment with opioids for pain related to either primary prostate cancer or metastasis within 28 days prior to Day 1 (Part 1) or randomization (Part 2).
Current use of potent P-gp inhibitors within 7 days prior to Day 1 (Part 1) or randomization (Part 2).
Major surgery (as defined by the investigator) within 2 weeks before Day 1 (Part 1) or randomization (Part 2), or palliative localized radiation therapy within 3 weeks before randomization (Part 2).
Clinically significant cardiovascular disease
Significant renal dysfunction as defined by any of the following laboratory abnormalities:
Renal: eGFR \< 30 mL/min/1.73 m2 by the MDRD equation (available via www.mdrd.com).
Patients enrolled in Part 1 only: Moderate renal impairment (eGFR 30-59 mL/min/1.73 m2) at screening.
Significant hepatic dysfunction as defined by any of the following laboratory abnormalities on screening labs:
Total serum bilirubin \>1.5 times the upper limit of normal (ULN) (\>3 × ULN for patients with documented Gilbert syndrome or for whom indirect bilirubin concentrations suggest an extrahepatic source of elevation).
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2.5 times ULN (\>5 × ULN if liver function abnormalities are due to hepatic metastasis).
+13 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Pfizerlead
Astellas Pharma Inccollaborator