A Phase 1 Study Of Talazoparib, PARP Inhibitor, In Japanese Patients With Advanced Solid Tumors

A PHASE 1 STUDY OF THE SAFETY, PHARMACOKINETICS AND ANTI-TUMOR ACTIVITY OF TALAZOPARIB, POLY (ADP-RIBOSE) POLYMERASE (PARP) INHIBITOR, IN JAPANESE PATIENTS WITH ADVANCED SOLID TUMORS

This is a Phase 1 study which consists of 2 parts; Dose Escalation part and Expansion part.

The dose escalation part is open-label, and evaluates safety, preliminary efficacy and PK of single-agent talazoparib in sequential cohorts of adult patients with advanced solid tumors who are resistant to standard therapy or for whom no standard therapy is available.

In the dose escalation part, up to 18 (minimum 3) patients are expected to be enrolled depending on the observed DLTs.

The expansion part is designed to assess the efficacy, safety and PK of single-agent talazoparib at RP2D determined in the dose escalation part in adult patients with locally advanced or metastatic breast cancer who have deleterious or suspected deleterious germline BRCA1 or BRCA2 mutations.

In the expansion part, a minimum of 17 patients will be enrolled evaluable for the primary endpoint.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasms; Breast Neoplasms
• Intervention / Treatment: Drug: talazoparib

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Kagoshima, Japan, 892-0833
    • Hakuaikai Medical Corporation Sagara Hospital
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 464-8681
      • Aichi Cancer Center Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Kanagawa Cancer Center
  • Saitama
    • Kitaadachi-gun, Saitama, Japan, 362-0806
      • Saitama Cancer Center
  • Tokyo
    • Chuo-Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

[Dose Escalation Part]

Inclusion Criteria:

• Histological or cytological diagnosis of locally advanced or metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available.
• ECOG Performance Status 0 or 1.
• Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

• Patients with known symptomatic brain metastases requiring steroids.
• Current use of a strong P-gp inhibitor, strong P-gp inducer, or strong inhibitor of BCRP within 1 week or 5 half lives which ever is longer prior to the first dose of study treatment.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

[Dose Expansion Part]

Inclusion Criteria:

• Histologically or cytologically confirmed carcinoma of the breast.
• Locally advanced breast cancer that is not amenable to curative radiation or surgery and/or metastatic disease.
• Documentation of a deleterious, suspected deleterious, or pathogenic germline BRCA1 or BRCA2 mutation by Myriad Genetics' BRACAnalysis CDx test.
• No more than 3 prior chemotherapy-inclusive regimens for locally advanced or metastatic disease.
• Have measurable lesion by the RECIST v.1.1.
• ECOG Performance Status 0-2.
• Adequate Bone Marrow, Renal and Liver Function.

Exclusion Criteria:

• First-line locally advanced or metastatic breast cancer with no prior neoadjuvant and adjuvant chemotherapy.
• Prior treatment with a PARP inhibitor.
• Objective disease progression while receiving platinum chemotherapy administered for locally advanced or metastatic disease.
• HER2 positive breast cancer.
• Active inflammatory breast cancer.
• Central nervous system (CNS) metastases.
• Current or anticipated use within 7 days prior to the first dose of study treatment, or anticipated use during the study of strong P-gp inhibitors.
• Fertile male patients and female patients of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: talazoparib; 0.75 mg/day or 1.0 mg/day	Drug: talazoparib; Talazoparib will be administered orally on a continuous basis. Talazoparib may be taken with or without food. Each cycle will consist of 28 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT)	DLT was defined as any of the following adverse events occurred in 1st treatment cycle and attributable to talazoparib: hematologic- grade(G) 4 neutropenia greater than (>)7days; Febrile neutropenia >1 hour; G greater than or equal to (>=)3 neutropenic infection, thrombocytopenia associated with G2 hemorrhage; G4 thrombocytopenia, anemia; G3 anemia required transfusion; daily dosing interrupted for >=7 total days in first cycle for G3 neutropenia/thrombocytopenia. Non-hematologic: any G>=3AE except non-clinically significant laboratory abnormalities, Non-hematologic AE deemed not clinically significant, nausea, vomiting, diarrhea responded to medical intervention within 72 hours, fatigue improved to G>=2 within 7 days. Alanine/aspartate aminotransferase (ALT/AST)>5*upper limit of normal(ULN) and 2*increases above baseline values; ALT/AST>=3*ULN concurrent with total bilirubin (TB)>2*ULN; TB>5*ULN; failure to deliver 75percent(%) of doses due to toxicities attributable to talazoparib.	Cycle 1 (28 days)
Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment	Confirmed OR in participants was defined as the percentage of participants with complete response (CR) or partial response (PR) as best response determined by investigator as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAE) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03	Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death.	From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03	A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Serious adverse event was the AE resulting in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. AE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Relatedness to study drug was assessed by the investigator.	From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Number of Participants With Grade 3 or Higher Treatment-Emergent Adverse Events (AEs) Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03	AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the events between first dose of study drug and up to 30 days after last dose or before start of new anticancer therapy, whichever occurred first. TEAE graded by CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher AEs were reported.	From start of the treatment up to 30 days after last dose or start of new anticancer therapy, whichever occurred first (Dose escalation: maximum duration- up to 286 days; Dose expansion: maximum duration- up to 502 days)
Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Chemistry	Parameters: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatinine increased, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.	Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days
Number of Participants With Laboratory Abnormalities Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03: Hematology	Hematological parameters included: Anemia, Hemoglobin increased, Lymphocyte count decreased, Lymphocyte count increased, Neutrophil count decreased, Platelet count decreased, White blood cell decreased. As per CTCAE v 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Only those categories in which at least one participant had data were reported in this outcome measure.	Dose escalation: Baseline up to 286 days; Dose expansion: Baseline up to 502 days
Dose Escalation: Number of Participants With Abnormalities in Vital Signs	Vital sign abnormalities: a) Sitting systolic blood pressure: <90 millimeter of mercury (mmHg), decrease from baseline >=30 mmHg, increase from baseline >=30 mmHg; b) Sitting diastolic blood pressure: minimum <50 mmHg, decrease from baseline >=20 mmHg, increase from baseline >=20 mmHg; c) Sitting pulse rate: minimum <40 beats per minute (bpm), maximum >120 bpm. Only those categories in which at least one participant had data were reported in this outcome measure.	Baseline up to 286 days
Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib	Cmax was defined as the maximum observed plasma concentration of talazoparib.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib	Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib	Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib	Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day -7 of Cycle 1
Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F)	Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib	Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf).	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1
Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib	Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib	Pre dose plasma concentration of talazoparib.	Pre dose on Day 22 of Cycle 1
Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib	Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose).	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib	Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau) at steady state (post multiple dose), where dosing interval was 24 hours.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss)	Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib	Accumulation ratio for AUC was calculated as AUCtau for Day 22 divided by AUCtau for Day -7, where AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours.	Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day -7 and Day 22 of Cycle 1
Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib	Rss was calculated by dividing AUCtau at steady state (post multiple dosing on Day 22) by single dose AUCinf (on Day -7). AUCtau was defined as area under the plasma concentration curve from time 0 to end of dosing interval, where dosing interval was 24 hours. AUCinf was defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).	Pre dose, 0.50, 0.75, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72 and 96 hours post dose on Day -7 of Cycle 1; Pre dose, 0.5, 0.75, 1, 2, 4, 6, 8, 10 and 24 hours post dose on Day 22 of Cycle 1
Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	OR in participants was defined as the percentage of participants with CR or PR as best response determined by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)
Dose Escalation: Progression Free Survival (PFS)	PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.	From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 286 days)
Dose Escalation: Duration of Response (DOR)	DOR was defined as the time between the date of the first documented objective response (PR or CR) and the date of the first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 286 days)
Dose Expansion: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)	Confirmed OR in participants was defined as the percentage of participants with CR or PR as best response determined by BICR as per RECIST v 1.1 and confirmed by a second image at least 4 weeks from the initial imaging showing response. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment	Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by investigator as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.	Baseline up to Week 16, Baseline up to Week 24
Dose Expansion: Percentage of Participants With Confirmed Disease Control as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)	Disease Control (DC) was defined as participants with a confirmed CR, confirmed PR and SD at 16 and 24 weeks as assessed by BICR as per RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.	Baseline up to Week 16, Baseline up to Week 24
Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment	TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)
Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)	TTR was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) as assessed by BICR according to RECIST v 1.1. As per RECIST v 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.	From first dose of study drug until first documentation of CR or PR (maximum duration: up to 502 days)
Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment	DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)	DOR was defined as the time between the date of first documented objective response (PR or CR) and the date of first documented progression or death (due to any cause) whichever occurs first. As per RECIST v 1.1: CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.	From date of first documented response to date of first documented PD or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment	PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.	From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)
Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR)	PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST v 1.1, or death due to any cause, whichever occurs first. PD = at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of >=5 mm or appearance of at least 1 new lesion.	From day of first dose until disease progression or death (due to any cause) whichever occur first (maximum duration: up to 502 days)
Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12	OS was defined as the time from the first dose date to date of death due to any cause. Participant was considered as event (overall survival) free if participant was not died and was alive at Month 12. Probability of participants who were event free at Month 12 was estimated by Kaplan-Meier method and reported.	At Month 12
Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib	Pre dose plasma drug concentration.	Pre dose at 0 hour on Day 1 of Cycle 2, 3, 4 and unplanned (any time during dose expansion period up to 502 days)

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Kotani H, Masuda N, Yamashita T, Naito Y, Taira T, Inoue K, Takahashi M, Yonemori K, Toyoizumi S, Mori Y, Nagasawa T, Hori N, Iwata H. Efficacy and safety of talazoparib in Japanese patients with germline BRCA-mutated locally advanced or metastatic breast cancer: results of the phase 1 dose-expansion study. Breast Cancer. 2022 Nov;29(6):1088-1098. doi: 10.1007/s12282-022-01390-w. Epub 2022 Jul 30.
• Naito Y, Kuboki Y, Ikeda M, Harano K, Matsubara N, Toyoizumi S, Mori Y, Hori N, Nagasawa T, Kogawa T. Safety, pharmacokinetics, and preliminary efficacy of the PARP inhibitor talazoparib in Japanese patients with advanced solid tumors: phase 1 study. Invest New Drugs. 2021 Dec;39(6):1568-1576. doi: 10.1007/s10637-021-01120-7. Epub 2021 Jun 23.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2017
• Primary Completion (Actual): January 11, 2021
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: November 11, 2017
• First Submitted That Met QC Criteria: November 11, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: breast cancer; PARP inhibitor; Japanese; Phase 1; solid tumors; talazoparib; PF-06944076; MDV3800; BMN673; C3441030
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Talazoparib
• Other Study ID Numbers: C3441030

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No