mCRPC
Conditions
Keywords
mCRPC (metastatic castration-resistant prostate cancer)
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.
Detailed description
Part 1 is an open-label, non-randomized, safety and PK run-in study designed to confirm the starting dose of talazoparib in combination with enzalutamide through assessment of target safety events and PK at select sites. Part 2 is a randomized, double-blind, placebo-controlled, multinational study comparing talazoparib plus enzalutamide vs. placebo plus enzalutamide in patients with mCRPC.
Interventions
Talazoparib 0.5 mg/day plus enzalutamide 160mg/day
DRUGPlacebo with enzalutamide
Placebo plus enzalutamide 160 mg/day
Sponsors
Pfizer
Astellas Pharma Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
To assess radiographic PFS in men with mCRPC (with no systemic treatments initiated after documentation of mCRCP) treated with talazoparib and enzalutamide vs. placebo plus enzalutamide
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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. Must agree not to donate sperm from the first dose of study drug to 4 months after the last dose of study drug. Evidence of a personally signed and dated informed consent document (and molecular prescreening consent if appropriate) indicating that the patient \[or a legally acceptable representative/legal guardian\] has been informed of all pertinent aspects of the study. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
Exclusion criteria
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 cytotoxic chemotherapy, biologic therapy including sipuleucel T, or radionuclide therapy received in the castration-sensitive prostate cancer is NOT exclusionary if discontinued in the 28 days prior to Day 1 (Part 1) or randomization (Part 2). 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). * Albumin \<2.8 g/dL Absolute neutrophil count \< 1500/µL, platelets \< 100,000/µL, or hemoglobin \< 9 g/dL (may not have received growth factors or blood transfusions within 14 days before obtaining the hematology values at screening). Known or suspected brain metastasis or active leptomeningeal disease. Symptomatic or impending spinal cord compression or cauda equina syndrome. Any history of myelodysplastic syndrome, acute myeloid leukemia, or prior malignancy except any of the following: * Carcinoma in situ or non melanoma skin cancer * Any prior malignancies ≥3 years before randomization with no subsequent evidence of recurrence or progression regardless of the stage. * Stage 0 or Stage 1 cancer \<3 years before randomization that has a remote probability of recurrence or progression in the opinion of the investigator Gastrointestinal disorder affecting absorption. Fertile male subjects who are unwilling or unable to use highly effective methods of contraception for the duration of the study and for 4 months after the last dose of investigational product. 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. Other acute or chronic medical (concurrent disease, infection, or comorbidity) or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that interferes with ability to participate in the study, 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. History of seizure or any condition that may predispose to seizure (eg, prior cortical stroke, significant brain trauma). Also, history of loss of consciousness or transient ischemic attack within 12 months of randomization (Part 2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Post dose on Day 1 up to Day 66 in 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. |
| 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 | Post dose on Day 1 up to Day 66 in 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. |
| Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | 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) | 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. |
| Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | 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) | 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. |
| Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | 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) | 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. |
| 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 | 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) | 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. |
| 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 | From the start of treatment to the time of first documented progression, or death (maximum up to 42 months) | 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. |
| BICR Assessed rPFS Per RECIST 1.1 in Patients With DDR Deficiencies - Part 2 | From the start of treatment to the time of first documented progression, or death (maximum up to 38 months) | 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. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, China, Czechia, Finland, France, Germany, Hungary, Israel, Italy, Japan, New Zealand, Norway, Peru, Poland, Portugal, South Africa, South Korea, Spain, Sweden, United Kingdom, United States
Contacts
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Participant flow
Recruitment details
As of the data cutoff for the primary completion date (PCD) on 16 Aug 2022 for Part 1 and Part 2 Cohort 1 and on 03 Oct 2022 for Part 2 Cohort 2, for overall study, 2896 participants were screened for participation in the C3441021 study. As of 03 Oct 2022, a total of 1054 participants were enrolled in this study.
Pre-assignment details
As of 16 Aug 2022, 19 participants were enrolled in Part 1, 805 participants with metastatic castrate-resistant prostate cancer (mCRPC) unselected for DNA damage response (DDR) deficiencies were randomized in Part 2 Cohort 1. As of 03 Oct 2022, 169 DDR-deficient participants enrolled in Cohort 1 were combined with the 230 DDR-deficient participants enrolled in Cohort 2 such that 399 participants were included in the analysis for participants with DDR deficiencies.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide Participants initially received a starting dose of talazoparib 1 mg once daily (QD) in combination with enzalutamide 160 mg QD up until Day 66, then the dose of talazoparib was reduced to 0.5 mg QD based on results from a review of available safety and pharmacokinetic (PK) data (up to a maximum of 231.14 weeks for both talazoparib and enzalutamide as of 16 Aug 2022). | 13 |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide Participants received talazoparib 0.5 mg QD in combination with enzalutamide 160 mg QD (up to a maximum of 180 weeks for talazoparib and 219.29 weeks for enzalutamide as of 16 Aug 2022). | 6 |
| Part 2 Cohort 1: Talazoparib+Enzalutamide (All-comer) Participants were randomized to receive talazoparib 0.5 mg QD in combination with enzalutamide 160 mg QD (up to a maximum of 186.14 weeks for both talazoparib and enzalutamide as of 16 Aug 2022). | 402 |
| Part 2 Cohort 1: Placebo+Enzalutamide (All-comer) Participants were randomized to receive placebo QD in combination with enzalutamide 160 mg QD (up to a maximum of 182 weeks for both placebo and enzalutamide as of 16 Aug 2022). | 403 |
| Part 2 Cohort 2: Talazoparib+Enzalutamide (DDR-deficient) Participants with DDR deficiencies were randomized to receive talazoparib 0.5 mg QD in combination with enzalutamide 160 mg QD (up to a maximum of 169.86 weeks for both talazoparib and enzalutamide as of 03 Oct 2022). | 115 |
| Part 2 Cohort 2: Placebo+Enzalutamide (DDR-deficient) Participants with DDR deficiencies were randomized to receive placebo QD in combination with enzalutamide 160 mg QD (up to a maximum of 157 weeks for both placebo and enzalutamide as of 03 Oct 2022). | 115 |
| Total | 1,054 |
Baseline characteristics
| Characteristic | Total | Part 1: Talazoparib 1 mg QD+Enzalutamide | Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Part 2 Cohort 1: Talazoparib+Enzalutamide (All-comer) | Part 2 Cohort 1: Placebo+Enzalutamide (All-comer) | Part 2 Cohort 2: Talazoparib+Enzalutamide (DDR-deficient) | Part 2 Cohort 2: Placebo+Enzalutamide (DDR-deficient) |
|---|---|---|---|---|---|---|---|
| Age, Customized 65-<75 years | 483 Participants | 8 Participants | 4 Participants | 188 Participants | 175 Participants | 53 Participants | 55 Participants |
| Age, Customized <65 years | 227 Participants | 1 Participants | 2 Participants | 79 Participants | 94 Participants | 25 Participants | 26 Participants |
| Age, Customized >=75 years | 344 Participants | 4 Participants | 0 Participants | 135 Participants | 134 Participants | 37 Participants | 34 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 272 Participants | 0 Participants | 0 Participants | 127 Participants | 120 Participants | 13 Participants | 12 Participants |
| Race/Ethnicity, Customized Black or African American | 23 Participants | 0 Participants | 0 Participants | 11 Participants | 5 Participants | 4 Participants | 3 Participants |
| Race/Ethnicity, Customized Multiracial | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 58 Participants | 0 Participants | 0 Participants | 19 Participants | 21 Participants | 8 Participants | 10 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 694 Participants | 12 Participants | 6 Participants | 243 Participants | 255 Participants | 88 Participants | 90 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 1054 Participants | 13 Participants | 6 Participants | 402 Participants | 403 Participants | 115 Participants | 115 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 13 | 2 / 6 | 123 / 402 | 129 / 403 | 43 / 200 | 53 / 199 |
| other Total, other adverse events | 13 / 13 | 6 / 6 | 377 / 398 | 351 / 401 | 190 / 198 | 182 / 199 |
| serious Total, serious adverse events | 6 / 13 | 3 / 6 | 157 / 398 | 107 / 401 | 60 / 198 | 40 / 199 |
Outcome results
Primary
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.
Time frame: From the start of treatment to the time of first documented progression, or death (maximum up to 38 months)
Population: Included DDR-deficient participants randomized to double-blind study treatment in Part 2 regardless of whether or not treatment was administered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | BICR Assessed rPFS Per RECIST 1.1 in Patients With DDR Deficiencies - Part 2 | NA Months |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | BICR Assessed rPFS Per RECIST 1.1 in Patients With DDR Deficiencies - Part 2 | 13.8 Months |
Comparison: The following statistical hypotheses was tested to address the primary objectives: H02: HRrPFS+ ≥1 vs H12: HRrPFS+ \<1, where HRrPFS and HRrPFS+ are the hazard ratios (talazoparib in combination with enzalutamide vs. placebo in combination with enzalutamide) of rPFS based on BICR assessment in the DDR deficient population for Part 2 Cohort 2.p-value: <0.000195% CI: [0.328, 0.61]Log Rank
Primary
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.
Time frame: From the start of treatment to the time of first documented progression, or death (maximum up to 42 months)
Population: Included all participants randomized to double-blind study treatment in Part 2 Cohort 1 regardless of whether or not treatment was administered.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | NA Months |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | 21.9 Months |
Comparison: The following statistical hypotheses was tested to address the primary objectives: H01: HRrPFS ≥1 vs H11: HRrPFS \<1, where HRrPFS and HRrPFS+ are the hazard ratios (talazoparib in combination with enzalutamide vs. placebo in combination with enzalutamide) of rPFS based on BICR assessment in the all-comers population for Part 2 Cohort 1.p-value: <0.000195% CI: [0.506, 0.777]Log Rank
Primary
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.
Time frame: Post dose on Day 1 up to Day 66 in Part 1
Population: Included all participants in Part 1 who received at least 1 dose of study intervention (talazoparib or enzalutamide).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 2 Anemia | 2 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Anemia | 6 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 1 Neutropenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 2 Neutropenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Neutropenia | 4 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 2 Leukopenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Leukopenia | 3 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Thrombocytopenia | 2 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Thrombocytopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 2 Anemia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Anemia | 1 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Leukopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 1 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 2 Leukopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 2 Neutropenia | 0 Participants |
Primary
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.
Time frame: 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)
Population: Included all participants in Part 1 who received at least 1 dose of study intervention (talazoparib or enzalutamide).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Anemia | 10 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 1 Neutropenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 2 Neutropenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Neutropenia | 6 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 2 Leukopenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Leukopenia | 5 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Thrombocytopenia | 3 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 4 Anemia | 0 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 2 Lymphopenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Lymphopenia | 2 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 4 Anemia | 1 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Anemia | 3 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Leukopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 1 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Lymphopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 2 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Thrombocytopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 3 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 2 Lymphopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality Clustered Treatment-Emergent Cytopenias by PT and Max CTCAE Grade Occuring Anytime After Dosing - Part 1 | Grade 2 Leukopenia | 0 Participants |
Primary
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.
Time frame: 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)
Population: Included all participants in Part 1 who received at least 1 dose of study intervention (talazoparib or enzalutamide).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with medication error TEAE | 0 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 3 or 4 TEAE | 11 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with serious TEAE | 6 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 5 TEAE | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with TEAEs | 13 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 5 TEAE | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with TEAEs | 6 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with medication error TEAE | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with serious TEAE | 3 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With All-Causality TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 3 or 4 TEAE | 6 Participants |
Primary
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.
Time frame: Post dose on Day 1 up to Day 66 in Part 1
Population: Included all participants in Part 1 who received at least 1 dose of study intervention (talazoparib or enzalutamide).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with medication error TEAE | 0 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with Maximum Grade 3 or 4 TEAE | 8 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with serious TEAE | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with Maximum Grade 5 TEAE | 0 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with TEAEs | 13 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with Maximum Grade 5 TEAE | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with TEAEs | 6 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with medication error TEAE | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with serious TEAE | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Occuring Within the First 66 Days of Dosing - Part 1 | Participants with Maximum Grade 3 or 4 TEAE | 1 Participants |
Primary
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.
Time frame: 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)
Population: Included all participants in Part 1 who received at least 1 dose of study intervention (talazoparib or enzalutamide).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Anemia | 10 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 1 Neutropenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 2 Neutropenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Neutropenia | 6 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 2 Leukopenia | 2 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Leukopenia | 4 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Thrombocytopenia | 3 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 4 Anemia | 0 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 2 Lymphopenia | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | 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 | Grade 3 Lymphopenia | 2 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 4 Anemia | 1 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Anemia | 3 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Leukopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 1 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Lymphopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 2 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Thrombocytopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 3 Neutropenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 2 Lymphopenia | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | 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 | Grade 2 Leukopenia | 0 Participants |
Primary
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.
Time frame: 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)
Population: Included all participants in Part 1 who received at least 1 dose of study intervention (talazoparib or enzalutamide).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with medication error TEAE | 0 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 3 or 4 TEAE | 10 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with serious TEAE | 2 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 5 TEAE | 1 Participants |
| Part 1: Talazoparib 1 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with TEAEs | 13 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 5 TEAE | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with TEAEs | 6 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with medication error TEAE | 0 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with serious TEAE | 1 Participants |
| Part 1: Talazoparib 0.5 mg QD+Enzalutamide | Number of Participants With Treatment-Related TEAEs During the Overall Period of Part 1 | Participants with Maximum Grade 3 or 4 TEAE | 4 Participants |