STUDY OF TALAZOPARIB MONOTHERAPY IN CHINESE PARTICIPANTS WITH ADVANCED SOLID TUMORS

NCT04635631 | Completed Phase 1 Results

• 1 other identifier: C3441049
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

A phase1 study to evaluate the PK (single dose and multiple doses) and safety of talazoparib 1 mg Once Daily in Chinese adult participants with advanced solid tumors. A maximum of approximately 15 participants will be enrolled such that approximately 12 evaluable participants complete the study.

Conditions

Neoplasms

Outcome Measures

Primary Outcomes (15)

• Maximum Observed Concentration (Cmax) of Talazoparib Following Single Oral Dose

  Maximum plasma concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Cmax was directly observed from data.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Time to Cmax (Tmax) of Talazoparib Following Single Oral Dose

  Time to reach Cmax (maximum plasma concentration) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Area Under Plasma Concentration-Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Talazoparib Following Single Oral Dose

  Area under the plasma concentration versus time curve from time zero to the time of the last quantifiable concentration of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Area Under the Plasma Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of Talazoparib Following Single Oral Dose

  Area under the plasma concentration versus time curve from time zero to the time tau (=24 hours) of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Apparent Oral Clearance (CL/F) of Talazoparib Following Single Oral Dose

  Apparent oral clearance of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F is calculated as dose/AUCinf. AUCinf = area under the plasma concentration versus time curve from time zero extrapolated to infinite time.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Apparent Volume of Distribution (Vz/F) of Talazoparib Following Single Oral Dose

  Apparent volume of distribution of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. Vz/F is calculated as Dose/(AUCinf \* kel), where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCinf is area under the plasma concentration versus time curve from time zero extrapolated to infinite time.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Terminal Half-Life (t1/2) of Talazoparib Following Single Oral Dose

  Terminal half-life of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9. t1/2 is defined as the time for plasma concentration of drug to decrease by one half.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Area Under Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) of Talazoparib Following Single Oral Dose

  Area under the plasma concentration versus time curve from time zero extrapolated to infinite time of talazoparib after the participant received a single oral lead-in dose of talazoparib 1 mg on Study Day -9.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours and 216 hours post Day -9 dosing

• Cmax of Talazoparib Following Multiple Oral Doses (Steady State)

  Maximum plasma concentration of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.

• Tmax of Talazoparib Following Multiple Oral Doses (Steady State)

  Time for Cmax of talazoparib at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.

• Minimum Plasma Concentration (Cmin) of Talazoparib Following Multiple Oral Doses (Steady State)

  Minimum plasma concentration observed during the dosing interval at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.

• AUCtau of Talazoparib Following Multiple Oral Doses (Steady State)

  Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.

• CL/F of Talazoparib Following Multiple Oral Doses (Steady State)

  Apparent clearance at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is a quantitative measure of the rate at which a drug substance is removed from the blood. Steady-state CL/F is calculated as dose/AUCtau. AUCtau = area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.

• Observed Accumulation Ratio (Rac) of Talazoparib Following Multiple Oral Doses (Steady State)

  Observed accumulation ratio at steady state after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rac is calculated as AUCtau/AUCsd,tau, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCsd,tau = area under the plasma concentration versus time curve from time zero extrapolated to the time tau (=24 hours) after single dose.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.

• Steady-State Accumulation Ratio (Rss) of Talazoparib Following Multiple Oral Doses (Steady State)

  Steady-state accumulation ratio after the participant received multiple oral doses of talazoparib 1 mg QD from Cycle 1 Day 1 to Cycle 1 Day 22. Rss is calculated as AUCtau/AUCinf, where AUCtau = Area under the plasma concentration versus time curve within a dosing interval of tau (=24 hours) at steady state after multiple doses, AUCinf = Area under the plasma concentration versus time curve from time zero extrapolated to infinite time after single dose.

  Pre-dose and 0.5 hours, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours after dosing on Cycle 1 Day 22.

Secondary Outcomes (19)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)

• Number of Participants With Serious Adverse Events (SAEs)

  Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)

• Number of Participants With Grade 3 or 4 All-Causality TEAEs by Preferred Term (PT) and Maximum CTCAE Grade

  Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)

• Number of Participants With Grade 3 or 4 Treatment-Related TEAEs by PT and Maximum CTCAE Grade

  Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)

• Number of Participants With TEAEs Leading to Dose Interruption of Talazoparib by PT

  Baseline (the latest non-missing value prior to or on the date of first dose of talazoparib) to at least 28 days after the last dose of talazoparib (maximum of approximately 46 weeks)

Study Arms (1)

talazoparib

EXPERIMENTAL

1 mg QD

Drug: talazoparib

Interventions

talazoparib DRUG

Talazoparib will be administered orally on a continuous basis. Each cycle will consist of 28 days.

talazoparib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Participants with brain metastases.
• Current or anticipated use of P gp inhibitor and/or inducer within 7 days prior to study intervention from lead-in to end of Cycle 1; concomitant use of potent P gp inhibitor after Cycle 1 until the end of treatment.
• Prior treatment with a PARP inhibitor.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Jilin Cancer Hospital

Changchun, Jilin, 130000, China

Location

Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

Related Publications (1)

• Luo Y, Cheng Y, Wu C, Ye H, Chen N, Zhang F, Wei H, Xu B. Pharmacokinetics, safety, and antitumor activity of talazoparib monotherapy in Chinese patients with advanced solid tumors. Invest New Drugs. 2023 Jun;41(3):503-511. doi: 10.1007/s10637-023-01351-w. Epub 2023 May 12.

  PMID: 37171721 DERIVED

Related Links

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

MeSH Terms

Conditions

Neoplasms

Interventions

talazoparib

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2020
• First Posted: November 19, 2020
• Study Start: November 30, 2020
• Primary Completion: August 8, 2021
• Study Completion: December 14, 2021
• Last Updated: October 10, 2023
• Results First Posted: October 10, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)