Trial Outcomes & Findings for A Study of Talazoparib in Patients With Advanced Solid Tumors (NCT NCT03070548)

NCT ID: NCT03070548

Last Updated: 2018-12-17

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose
• Results posted on: 2018-12-17

Participant Flow

This is a mass balance study with 14C-radiolabeled talazoparib in at least 6 participants with advanced solid tumors who qualified for treatment with talazoparib. Participants who completed the mass-balance part in this study had the option to continue treatment on an open-label extension protocol.

Participant milestones

Measure	Talazoparib Participants with advanced solid tumors received a single dose of talazoparib 1 miligram (mg) oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Talazoparib in Patients With Advanced Solid Tumors

Baseline characteristics by cohort

Measure	Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).
Age, Continuous	50.2 years STANDARD_DEVIATION 17.61 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: Pharmacokinetic (PK) population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Maximum Observed Plasma Concentration (Cmax) of Talazoparib

8.4 nanogram per milliliter (ng/mL) Standard Deviation 3.8

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Time to Attain Maximum Observed Plasma Concentration (Tmax) of Talazoparib

0.5 hours Interval 0.5 to 0.5

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf).

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of Talazoparib

129.9 hour*nanogram per milliliter (hr*ng/mL) Standard Deviation 70.4

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Talazoparib

118.9 hr*ng/mL Standard Deviation 65.4

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Terminal elimination half-life was defined as time measured for the plasma concentration of talazoparib to decrease by one half.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Terminal Elimination Half-Life (t1/2) of Talazoparib

89.8 hours Standard Deviation 57.6

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Clearance of a drug was measure of the rate at which a drug was metabolized or eliminated by normal biological processes.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Apparent Total Plasma Clearance (CL/F) of Talazoparib

8.39 liter/hour Standard Deviation 3.7

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Apparent volume of distribution was 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 the drug.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Apparent Volume of Distribution (Vd/F) of Talazoparib

922.6 liter Standard Deviation 445.8

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Maximum Observed Plasma Concentration (Cmax) of 14C- Radioactivity

12.1 nanogram equivalent/mililiter Standard Deviation 5.8

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Time to Attain Maximum Observed Plasma Concentration (Tmax) of 14C- Radioactivity

0.5 hours Interval 0.5 to 0.5

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity

222.9 hour*nanogram equivalent/mililiter Standard Deviation 108.8

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity

199.3 hour*nanogram equivalent/mililiter Standard Deviation 101.9

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Terminal elimination half-life was defined as the time measured for the plasma radioactivity concentration to decrease by one half. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Terminal Elimination Half-Life (t1/2) of 14C- Radioactivity in Plasma

96.2 hours Standard Deviation 55.1

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Apparent Total Plasma Clearance (CL/F) of 14C- Radioactivity

5.35 liter/hour Standard Deviation 2.35

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Apparent volume of distribution was 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. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Plasma

655.8 liter Standard Deviation 338.1

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Maximum Observed Whole Blood Concentration (Cmax) of 14C- Radioactivity

12.5 nanogram equivalent/mililiter Standard Deviation 5.7

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Time to Attain Maximum Observed Whole Blood Concentration (Tmax) of 14C- Radioactivity

0.5 hours Interval 0.5 to 0.5

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of 14C- Radioactivity

234.1 hour*nanogram equivalent/mililiter Standard Deviation 114.1

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of 14C- Radioactivity

205.8 hour*nanogram equivalent/mililiter Standard Deviation 101.0

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Clearance of a drug was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Apparent Total Whole Blood Clearance (CL/F) of 14C- Radioactivity

5.21 liter/hour Standard Deviation 2.51

PRIMARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Apparent volume of distribution was 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 the drug. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Apparent Volume of Distribution (Vd/F) of 14C- Radioactivity in Whole Blood

484.4 liter Standard Deviation 237.5

PRIMARY outcome

Timeframe: Pre-dose, 0 to 8 hours (hrs), 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Ae t1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2).

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Amount of Talazoparib Excreted in Urine During Each Collection Interval (Ae t1-t2)

366.07 micrograms Standard Deviation 45.56

PRIMARY outcome

Timeframe: Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Aet1-t2% was the percentage of Aet1-t2, where Aet1-t2 was defined as the amount of talazoparib excreted into urine during each collection interval (t1-t2).

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Percentage of Dose of Talazoparib Excreted During Each Collection Interval (Aet1-t2%) of Talazoparib

40.92 percentage of dose Standard Deviation 4.324

PRIMARY outcome

Timeframe: Pre-dose, 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs, 48 to 72 hrs, 72 to 96 hrs and then after every 24 hrs until up to 504 hrs post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Renal clearance was calculated as cumulative amount of drug excreted in urine divided by AUC(0-last) (area under the plasma concentration-time curve from zero to the time of the last measurable concentration).

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Renal Clearance (CLr) of Talazoparib

3.808 liter/hour Standard Deviation 1.979

PRIMARY outcome

Timeframe: From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

Recovery of 14C-radioactivity in urine and feces was calculated in terms of percentage of administered dose after administration of a single 1 mg dose of oral solution (containing 100 micro-curie 14C-labeled talazoparib).

Outcome measures

Measure	Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).
The Recovery of 14C-Radioactivity as a Percentage of the Administered Dose Urine	68.647 Percentage of dose Standard Deviation 8.592
The Recovery of 14C-Radioactivity as a Percentage of the Administered Dose Feces	19.669 Percentage of dose Standard Deviation 5.493

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

100 micro-curie of 14C radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Ratio of Maximum Observed Plasma Concentration to Maximum Observed Whole Blood Concentration for 14C- Radioactivity

1.050 ratio Standard Deviation 0.0625

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-inf) was defined as the area under the plasma concentration-time curve from time zero (pre-dose) to extrapolated infinite time (0-inf). 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Infinity for 14C- Radioactivity

1.047 ratio Standard Deviation 0.1155

SECONDARY outcome

Timeframe: Pre-dose, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, 120, 168, 216, 264, 336, 384, 432 and 504 hours post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

AUC(0-last) was defined as the area under the plasma concentration-time curve from zero to the time of the last measurable concentration. 100 micro-curie of 14C-radiolabeled talazoparib was present in 1 mg of talazoparib.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Ratio of Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration to Area Under the Whole Blood Concentration-Time Curve From Time Zero to Last Quantifiable for 14C- Radioactivity

1.037 ratio Standard Deviation 0.1243

SECONDARY outcome

Timeframe: Day 1 to 14 days after last day of mass balance phase and at least 30 days after Day1/before initiation of new cytotoxic chemotherapy, new investigational treatment/first day of extension protocol, whichever occurs first(up to maximum duration of 8 weeks)

Population: Safety analysis set included all participants who received at least 1 dose of talazoparib.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent were events between first dose of study drug through 14 days after the last day of mass balance phase and at least 30 days after Day 1 or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first (up to maximum duration of 8 weeks from screening to follow-up for each participant) or before initiation of new cytotoxic chemotherapy, new investigational treatment, or the first day of extension protocol, whichever occurs first, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-serious (AEs) and serious adverse events (SAEs).

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Number of Participants With Treatment Emergent Adverse Events (AEs)

4 participants

SECONDARY outcome

Timeframe: Baseline up to Day 22

Population: Safety analysis set included all participants who received at least 1 dose of talazoparib.

Vital Signs included heart rate, respiratory rate, body temperature, systolic blood pressure and diastolic blood pressure. clinical significance of vital signs was determined at the investigator's discretion.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Number of Participants With Clinically Significant Vital Signs Parameters

0 participants

SECONDARY outcome

Timeframe: Baseline up to Day 22

Population: Safety population set included all participants who received at least 1 dose of talazoparib.

Criteria for clinically significant ECG abnormalities : Heart Rate; increase from baseline greater than (>)25 %and to a value >100, decrease from baseline >25% and to a value < 50; PR Interval: increase from baseline >25% and to a value >200; QRS Duration: increase from baseline >25% and to a value >100; QT interval using Fridericia's correction (QTcF): ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec; QT Interval: ranges >450 msec, >480 msec, >500 msec, Increase from baseline >30 msec and >60 msec.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Number of Participants With Clinically Significant Electrocardiogram (ECG) Abnormalities

0 participants

SECONDARY outcome

Timeframe: Baseline up to Day 22

Population: Safety population set included all participants who received at least 1 dose of talazoparib.

Haematological, biochemistry and urinalysis parameters. Biochemistry parameters:alkaline phosphatase 30-120units per liter(U/L), creatinine 53-110micromole/L(micromol/L), gamma glutamyl transferase 7-50U/L, glucose 3.3-5.5millimoles/L(mmol/L), lactate dehydrogenase 200-460U/L, triglycerides 0.4-1.7mmol/L, cholesterol 2.6-5.2mmol/L, phosphate 0.8-1.45mmol/L, sodium 135-146mmol/L, urea 2.8-7.2mmol/L, chloride 95-109mmol/L, creatine kinase 24-170U/L, aspartate aminotransferase 4-46U/L, potassium 3.5-5.5mmol/L. Haematology parameters:haemoglobin 120-155 gram/L(g/L), erythrocytes 4-5.2 10^12/L, haematocrit 0.35-0.45, prothrombin time 13.7-15.6 second(sec), lymphocytes 1-3.7 10^9/L, platelets 150-400 10^9/L, prothrombin intl. normalized ratio 0.89-1.1, activated partial thromboplastin time 25-43 sec, basophils 0-0.09 10^9/L, neutrophils 1.5-7 10^9/L, and leukocytes 4-10 10^9/L. Urinalysis parameters:urinalysis specific gravity 1.012-1.03, urinalysis pH 4.8-7.8.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Number of Participants With Clinically Significant Laboratory Abnormalities

0 participants

SECONDARY outcome

Timeframe: Baseline up to Day 22

Population: Safety population set included all participants who received at least 1 dose of talazoparib.

Physical examination included examination of abdomen, cardiovascular, eyes, ears, nose, throat, general appearance, head, neck, thyroid, lymph nodes, musculoskeletal, neurological, skin/subcutaneous tissue and thorax/lungs.

Outcome measures

Measure

Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).

Number of Participants With Change From Baseline in Physical Examination Findings

0 participants

SECONDARY outcome

Timeframe: From 0 to 8 hrs, 8 to 24 hrs, 24 to 48 hrs and then after every 24 hrs until up to 504 hrs post-dose

Population: PK population included all participants who received talazoparib and had at least 1 sample with sufficient concentration data.

M4 (M481/1, cysteine conjugate of mono-desfluoro-talazoparib) metabolite was found in urine. MDV10595 (M1, dehydrogenated talazoparib (PF-07052386), M556/1 (glucuronide conjugate of talazoparib), and M2 (M396/1, mono-oxidative talazoparib) metabolites were calculated together and were also found in urine. Three metabolites named as: MDV10595 (M1)/M556/1 and M2 (M396/1) which were calculated together were detected in feces. Amount of metabolite in this outcome measure was measured in terms of percentage of dose of talazoparib.

Outcome measures

Measure	Talazoparib n=6 Participants Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).
Amount of Any Significant Metabolites of Talazoparib in Urine and Feces M481/1: Urine	4.2 percentage of dose
Amount of Any Significant Metabolites of Talazoparib in Urine and Feces MDV10595+M556/1+M396/1: Urine	0.8 percentage of dose
Amount of Any Significant Metabolites of Talazoparib in Urine and Feces MDV10595+M556/1+M396/1: Feces	1.5 percentage of dose

Adverse Events

Talazoparib

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Talazoparib n=6 participants at risk Participants with advanced solid tumors received a single dose of talazoparib 1 mg oral solution (containing approximately 100 micro Curie of 14C-talazoparib) on Day 1. Participants were followed-up within 14 days after the last day of mass balance phase and at least 30 days after Day 1 or the first day of extension protocol, whichever occurred first (up to maximum duration of 8 weeks from screening to follow-up for each participant).
Gastrointestinal disorders Constipation	16.7% 1/6 • Day1 up to 14days after last day of mass balance phase and at least 30days after Day1/ before initiation of new cytotoxic chemotherapy, new investigational treatment/ first day of extension protocol, whichever occurs first (up to maximum duration of 8weeks from screening to follow-up for each participant) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who had received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	16.7% 1/6 • Day1 up to 14days after last day of mass balance phase and at least 30days after Day1/ before initiation of new cytotoxic chemotherapy, new investigational treatment/ first day of extension protocol, whichever occurs first (up to maximum duration of 8weeks from screening to follow-up for each participant) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who had received at least 1 dose of study drug.
Musculoskeletal and connective tissue disorders Pain in extremity	16.7% 1/6 • Day1 up to 14days after last day of mass balance phase and at least 30days after Day1/ before initiation of new cytotoxic chemotherapy, new investigational treatment/ first day of extension protocol, whichever occurs first (up to maximum duration of 8weeks from screening to follow-up for each participant) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who had received at least 1 dose of study drug.
Nervous system disorders Paraesthesia	16.7% 1/6 • Day1 up to 14days after last day of mass balance phase and at least 30days after Day1/ before initiation of new cytotoxic chemotherapy, new investigational treatment/ first day of extension protocol, whichever occurs first (up to maximum duration of 8weeks from screening to follow-up for each participant) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who had received at least 1 dose of study drug.
Nervous system disorders Dizziness	33.3% 2/6 • Day1 up to 14days after last day of mass balance phase and at least 30days after Day1/ before initiation of new cytotoxic chemotherapy, new investigational treatment/ first day of extension protocol, whichever occurs first (up to maximum duration of 8weeks from screening to follow-up for each participant) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who had received at least 1 dose of study drug.
Renal and urinary disorders Pollakiuria	16.7% 1/6 • Day1 up to 14days after last day of mass balance phase and at least 30days after Day1/ before initiation of new cytotoxic chemotherapy, new investigational treatment/ first day of extension protocol, whichever occurs first (up to maximum duration of 8weeks from screening to follow-up for each participant) Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 participant and as non-serious in another participant or 1 participant may have experienced both serious and non-serious event during study. Safety analysis set included all participants who had received at least 1 dose of study drug.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
• Publication restrictions are in place

Restriction type: OTHER