A Phase 1 interventional study of talazoparib in Neoplasms and Breast Neoplasms, sponsored by Pfizer. Completed at 8 sites in Japan. Open to participants aged 20 Years and older. Per ClinicalTrials.gov, last updated 2024-08-22.
Sponsored by Pfizer · Phase 1, Interventional, and Treatment
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Among 22 studies testing talazoparib in Breast Neoplasms — 5 open to participants now, 7 under way, none of them phase 3. talazoparib · Breast Neoplasms.
Among the 22 studies testing talazoparib in Breast Neoplasms, this one is the 14th largest by enrollment, is the only one that started in 2017, is one of 6 in phase 1, and was the 9th registered.
14,832 studies on the registry are indexed under Breast Neoplasms; 3,320 are open to participants now.
Browse Breast Neoplasms studies →5 of the 22 studies testing talazoparib in Breast Neoplasms are open now, in 4 countries. Recruiting first, the newest first:
Massachusetts General Hospital · Sites in United States
Ages 18+ · Women only
Seoul National University Hospital · Sites in Korea, Republic of
Ages 19+ · Women only
National University Hospital, Singapore · Sites in Singapore
Ages 18–99
Erasmus Medical Center · Sites in Netherlands
Ages 18+
QuantumLeap Healthcare Collaborative · Sites in United States
Ages 18+
By country, each count listing its studies:
talazoparib: first FDA approval 2018 (TALZENNA), first EMA approval 2019. What it is approved for, and how studies give it, is on its page →
Of the 2,399 Breast Neoplasms studies recruiting now, 1,570 (65%) set no upper age limit and 592 (25%) stop at 75 or younger; 103 take children under 18; 215 take healthy volunteers.
This study: 20 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
22 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 9 · Phase 2 15 · Phase 3 1
First in 2010; this study’s year is marked. 1 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 28 is below the median of 72 across 10,903 interventional studies indexed under Breast Neoplasms.
Median enrollment 33 across the 22 interventional studies. Of the 11 that completed or were terminated, 9 (82%) have results posted.
This tab as a report to print or save as PDF → With an account.
5 of 22 have an industry lead sponsor. The 10 most frequent:
Pfizer is the lead sponsor of 3,337 studies on the registry; 150 are open to participants now.
Of its 601 completed or terminated interventional studies of FDA-regulated products, 392 (65%) have results posted.
182 studies in Breast Neoplasms by Pfizer: 6 open now, 26 under way, 7 of them phase 3. Of 145 finished, 94 (65%) have results posted.
Among the 182 studies in Breast Neoplasms by Pfizer, this one is the 91st largest by enrollment of the 121 interventional ones that give a count, is one of 7 that started in 2017, is one of 37 in phase 1, and was the 101st registered.
Pfizer’s Breast Neoplasms studies by the year they started, since 1998.
4 of the studies testing talazoparib in Breast Neoplasms that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT03990896Massachusetts General HospitalEvaluation of Talazoparib, a PARP Inhibitor, in Patients With Somatic BRCA Mutant Metastatic Breast Cancer: Genotyping Based Clinical Trial | 2027-03-31 |
| NCT03964532Georgetown UniversityTALAVE: Induction Talazoparib Followed by Combination of Talazoparib and Avelumab in Advanced Breast Cancer | 2027-04 |
| NCT04892693Seoul National University HospitalTalazoparib in Advanced Breast Cancer Patients With Homologous Recombinant Deficiency | 2027-05-31 |
| NCT05035745National University Hospital, SingaporeSelinexor & Talazoparib in Advanced Refractory Solid Tumors; Advanced/Metastatic Triple Negative Breast Cancer (START) | 2027-11 |
Add all 4 to your calendar (.ics) → With an account.
Among the 22 studies testing talazoparib in Breast Neoplasms, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Pfizer’s 182 in Breast Neoplasms:
This tab as a report to print or save as PDF → With an account.
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.
14,832 studies on the registry are indexed under Breast Neoplasms; 3,320 are open to participants now.
This study's enrollment of 28 is below the median of 72 across 10,903 interventional studies indexed under Breast Neoplasms.
Browse Breast Neoplasms studies →Pfizer is the lead sponsor of 3,337 studies on the registry; 150 are open to participants now.
Of its 601 completed or terminated interventional studies of FDA-regulated products, 392 (65%) have results posted.
Compared within Breast Neoplasms, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Neoplasms. The counts are of registry records indexed under each term, refreshed daily. How we classify →
[Dose Escalation Part]
Inclusion Criteria:
Exclusion Criteria:
[Dose Expansion Part]
Inclusion Criteria:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
Time frame: 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.
Time frame: From start of the treatment until disease progression or death (due to any cause) whichever occurred first (maximum duration: up to 502 days)
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: At Month 12
Dose Expansion: Trough Concentrations (Ctrough) of Talazoparib
Pre dose plasma drug concentration.
Time frame: 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)
This study included 2 periods: dose escalation and dose expansion. The recommended dose for dose expansion period of talazoparib was determined in dose escalation period.
| Milestone | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| Started | 3 | 6 | 0 |
| Completed | 0 | 0 | 0 |
| Not completed | 3 | 6 | 0 |
| Withdrew: Progressive disease | 2 | 6 | 0 |
| Withdrew: Global deterioration of health status | 1 | 0 | 0 |
| Milestone | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| Started | 0 | 0 | 19 |
| Completed | 0 | 0 | 0 |
| Not completed | 0 | 0 | 19 |
| Withdrew: Progressive disease | 0 | 0 | 11 |
| Withdrew: Ongoing | 0 | 0 | 8 |
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.
| Participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation: Number of Participants With Dose-Limiting Toxicities (DLT) | 0 | 0 |
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.
| Percentage of participants | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| 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 | 57.9 (36.8 to 77.0) |
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.
| Participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| 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 | 3 | 6 | 19 |
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.
| Participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| Number of Participants With Treatment Related Adverse Events Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version 4.03 | 2 | 3 | 19 |
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.
| Participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| 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 | 1 | 2 | 11 |
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.
| Participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| Alanine aminotransferase increased: Grade 1 | 1 | 2 | 8 |
| Alanine aminotransferase increased: Grade 2 | 0 | 0 | 1 |
| Alkaline phosphatase increased: Grade 1 | 1 | 2 | 4 |
| Alkaline phosphatase increased: Grade 2 | 0 | 1 | 1 |
| Aspartate aminotransferase increased: Grade 1 | 1 | 3 | 7 |
| Blood bilirubin increased: Grade 1 | 0 | 0 | 2 |
| Creatinine increased: Grade 1 | 2 | 6 | 17 |
| Hyperglycemia: Grade 1 | 0 | 0 | 1 |
| Hyperkalemia: Grade 1 | 1 | 0 | 0 |
| Hypermagnesemia: Grade 1 | 0 | 0 | 1 |
| Hypernatremia: Grade 1 | 0 | 1 | 1 |
| Hypoalbuminemia: Grade 1 | 2 | 2 | 6 |
| Hypoalbuminemia: Grade 2 | 0 | 1 | 0 |
| Hypocalcemia: Grade 1 | 1 | 2 | 9 |
| Hypoglycemia: Grade 1 | 0 | 0 | 1 |
| Hypomagnesemia: Grade 1 | 0 | 1 | 2 |
| Hyponatremia: Grade 1 | 1 | 1 | 2 |
| Hypophosphatemia: Grade 2 | 1 | 1 | 2 |
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.
| Participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| Anemia: Grade 1 | 3 | 2 | 8 |
| Anemia: Grade 2 | 0 | 3 | 0 |
| Anemia: Grade 3 | 0 | 1 | 9 |
| Lymphocyte count decreased: Grade 1 | 1 | 2 | 6 |
| Lymphocyte count decreased: Grade 2 | 2 | 3 | 4 |
| Lymphocyte count decreased: Grade 3 | 0 | 1 | 2 |
| Neutrophil count decreased: Grade 2 | 1 | 0 | 7 |
| Neutrophil count decreased: Grade 3 | 0 | 1 | 4 |
| Platelet count decreased: Grade 1 | 1 | 1 | 10 |
| Platelet count decreased: Grade 2 | 0 | 1 | 1 |
| White blood cell decreased: Grade 1 | 1 | 2 | 1 |
| White blood cell decreased: Grade 2 | 1 | 1 | 9 |
| White blood cell decreased: Grade 3 | 0 | 1 | 2 |
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.
| Participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Systolic blood pressure: <90 mmHg | 1 | 0 |
| Systolic blood pressure: decrease from baseline >=30 mmHg | 0 | 2 |
Cmax was defined as the maximum observed plasma concentration of talazoparib.
| Nanogram per milliliter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Maximum Observed Plasma Concentration (Cmax) for Talazoparib | 7.244 ± 34 | 13.78 ± 26 |
Tmax was defined as the time to reach maximum observed plasma concentration of talazoparib.
| Hours | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Talazoparib | 0.983 (0.750 to 1.92) | 0.967 (0.467 to 1.98) |
Area under the plasma concentration time-curve from time zero to the time of last measured concentration (AUClast).
| Nanogram hour per milliliter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Talazoparib | 97.48 ± 17 | 159.1 ± 33 |
Area under the plasma concentration curve from time 0 to end of dosing interval (AUCtau), where dosing interval was 24 hours.
| Nanogram hour per milliliter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Time Tau (AUCtau) for Talazoparib | 46.55 ± 20 | 85.39 ± 44 |
Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
| Liter per hour | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Apparent Oral Clearance of Talazoparib (CL/F) | 6.968 ± 12 | 5.010 ± 9 |
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.
| Liter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Apparent Volume of Distribution (Vz/F) for Talazoparib | 551.8 ± 42 | 361.1 ± 20 |
Terminal half-life (t1/2) is the time measured for the plasma concentration of a drug to decrease by half of its initial concentration.
| Hours | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Terminal Half-Life (t1/2) for Talazoparib | 56.60 ± 17.860 | 50.73 ± 10.121 |
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre dose) to extrapolated infinite time (0-inf).
| Nanogram hour per milliliter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Single Dose: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for Talazoparib | 107.5 ± 12 | 199.7 ± 9 |
Css,max is maximum observed plasma concentration at steady state (post multiple dose) of Talazoparib.
| Nanogram per milliliter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Multiple Dose: Maximum Observed Plasma Concentration at Steady State (Css,Max) for Talazoparib | 14.44 ± 26 | 32.84 ± 14 |
Pre dose plasma concentration of talazoparib.
| Nanogram per milliliter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Multiple Dose: Predose Concentration (Cmin) for Talazoparib | 2.175 ± 8 | 3.645 ± 49 |
Tss,max = Time to reach Cmax for talazoparib at steady state (post multiple dose).
| Hours | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Multiple Dose: Time for Maximum Observed Plasma Concentration at Steady State (Tss,Max) for Talazoparib | 1.02 (0.967 to 1.87) | 1.03 (0.733 to 1.92) |
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.
| Nanogram hour per milliliter | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Multiple Dose: Area Under the Curve From Time Zero to Time Tau at Steady State (AUCss,Tau) for Talazoparib | 127.2 ± 6 | 244.7 ± 21 |
Clearance is a measure of the rate at which a drug was metabolized or eliminated by normal biological processes.
| Liter per hour | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Multiple Dose: Apparent Oral Clearance of Talazoparib at Steady State (CL/Fss) | 5.898 ± 7 | 4.086 ± 21 |
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.
| Ratio | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Multiple Dose: Accumulation Ratio (Rac) of AUCtau for Talazoparib | 2.734 ± 24 | 2.866 ± 64 |
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).
| Ratio | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation- Multiple Dose: Linearity Ratio (Rss) of AUC for Talazoparib | 1.181 ± 12 | 1.249 ± 14 |
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.
| Percentage of participants | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation: Percentage of Participants With Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | 0 | 0 |
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.
| Months | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg |
|---|---|---|
| Dose Escalation: Progression Free Survival (PFS) | 3.0 (2.1 to 3.0) | 3.4 (1.2 to 9.6) |
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.
No measurements were reported for this outcome.
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.
| Percentage of participants | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| 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) | 52.6 (32.0 to 72.6) |
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.
| Percentage of participants | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Up to Week 16 | 94.7 (77.4 to 99.7) |
| Up to Week 24 | 94.7 (77.4 to 99.7) |
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.
| Percentage of participants | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Up to Week 16 | 89.5 (70.4 to 98.1) |
| Up to Week 24 | 89.5 (70.4 to 98.1) |
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.
| Months | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Dose Expansion: Time-to-Tumor Response (TTR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 2.63 (1.2 to 9.4) |
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.
| Months | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| 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) | 2.07 (1.2 to 4.2) |
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.
| Months | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 6.8 (2.7 to NA) |
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.
| Months | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Dose Expansion: Duration of Response (DOR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | 6.0 (2.3 to NA) |
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.
| Months | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 7.2 (4.1 to NA) |
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.
| Months | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Dose Expansion: Progression Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Blinded Independent Central Review (BICR) | 7.2 (3.9 to NA) |
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.
| Probability of event free participants | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Dose Expansion: Overall Survival (OS): Probability of Participants Who Were Event-Free at Month 12 | 0.847 (0.575 to 0.951) |
Pre dose plasma drug concentration.
| Picogram per milliliter | Dose Expansion: Talazoparib 1.0 mg |
|---|---|
| Cycle 2 Day 1 | 3098 ± 40 |
| Cycle 3 Day 1 | 3423 ± 41 |
| Cycle 4 Day 1 | 2910 ± 52 |
| Unplanned | 3670 ± 38 |
Collected over Dose escalation: maximum duration up to 286 days; Dose expansion: maximum duration up to 502 days. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dose Escalation: Talazoparib 0.75 mg | 0/3 (0%) | 1/3 (33.3%) | 3/3 (100%) |
| Dose Escalation: Talazoparib 1.0 mg | 0/6 (0%) | 0/6 (0%) | 6/6 (100%) |
| Dose Expansion: Talazoparib 1.0 mg | 2/19 (10.5%) | 1/19 (5.3%) | 19/19 (100%) |
| Event | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| Brain cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/3 | 0/6 | 0/19 |
| CholelithiasisHepatobiliary disorders | 0/3 | 0/6 | 1/19 |
| Event | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg |
|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 0/3 | 2/6 | 13/19 |
| Neutrophil count decreasedInvestigations | 1/3 | 1/6 | 12/19 |
| White blood cell count decreasedInvestigations | 0/3 | 1/6 | 8/19 |
| StomatitisGastrointestinal disorders | 0/3 | 2/6 | 7/19 |
| Alanine aminotransferase increasedInvestigations | 1/3 | 1/6 | 1/19 |
| Platelet count decreasedInvestigations | 0/3 | 2/6 | 6/19 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 1/3 | 0/6 | 1/19 |
| DysgeusiaNervous system disorders | 1/3 | 0/6 | 2/19 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 0/3 | 2/6 | 1/19 |
| Otitis media acuteInfections and infestations | 1/3 | 0/6 | 0/19 |
Full analysis set (FAS) included all participants assigned to study treatment and who took at least 1 dose of study treatment.
| Age, Customized(Participants) | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg | Total |
|---|---|---|---|---|
| Less than (<)18 Years | 0 | 0 | 0 | 0 |
| 18-44 Years | 1 | 0 | 7 | 8 |
| 45-64 Years | 1 | 3 | 6 | 10 |
| Greater than or equal to (>=)65 Years | 1 | 3 | 6 | 10 |
| Sex: Female, Male(Participants) | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg | Total |
|---|---|---|---|---|
| Female | 2 | 3 | 19 | 24 |
| Male | 1 | 3 | 0 | 4 |
| Ethnicity (NIH/OMB)(Participants) | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg | Total |
|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 3 | 6 | 19 | 28 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Dose Escalation: Talazoparib 0.75 mg | Dose Escalation: Talazoparib 1.0 mg | Dose Expansion: Talazoparib 1.0 mg | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 3 | 6 | 19 | 28 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 |
| White | 0 | 0 | 0 | 0 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — 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.
Ran from Nov 2017 to primary completion in Jan 2021, 37 months.
Results were first posted in Mar 2022, 1 year 1 month after primary completion.
Of 389 industry-sponsored phase 1 interventional studies under Breast Neoplasms, half reached primary completion within 39 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 56. This study's 37 months is close to that.
Counting every sponsor, half of 761 studies reached it within 44 months; a quarter within 25 and three quarters within 65.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jul 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Talazoparib