A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors

NCT04672460 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: C34410372020-006101-35
• Study Type: interventional
• Target: 73
• Locations: 2 countries
• Sites: 31

Brief Summary

This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple dosing under fasting conditions in participants with advanced solid tumors. In addition, the effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be evaluated in fixed sequence after the 2 BE assessment periods.

Conditions

Advanced Solid Tumors; Solid Tumors; Ovarian Cancer; Breast Cancer; Prostate Cancer; NSCLC; Pancreatic Cancer; Colorectal Cancer

Keywords

PARP inhibitor; Talazoparib; Talzenna; BRCA mutation; ATM mutation; Pharmacokinetics; Bioequivalence; Bioavailability; Food effect

Outcome Measures

Primary Outcomes (4)

• Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fasted Conditions

  AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

• Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fasted Conditions

  Cmax was the maximum observed plasma concentration and was directly observed from data. The geometric coefficient of variation was expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

• Area Under the Plasma Concentration-Time Profile From Time 0 to 24 Hours (AUC24) of Talazoparib After Multiple Dosing Under Fed Conditions

  AUC24 was defined as area under the plasma concentration-time profile from time zero to 24 hours post dose. The geometric coefficient of variation is expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

• Maximum Observed Plasma Concentration (Cmax) of Talazoparib After Multiple Dosing Under Fed Conditions

  Cmax was the maximum observed plasma concentration and was directly observed from data. The geometric coefficient of variation was expressed in percentage. The ratio (Test/Reference) of adjusted means and 90% CI were expressed as percentages.

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

Secondary Outcomes (6)

• Apparent Clearance After Oral Dose (CL/F) of Talazoparib After Multiple Dosing

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

• Time of Observed Maximum Plasma Concentration (Tmax) of Talazoparib After Multiple Dosing

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

• Area Under the Plasma Concentration-Time Profile From Time 0 to Time of the Last Quantifiable Concentration (AUClast) of Talazoparib After Multiple Dosing

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2 and predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

• Predose Concentration During Multiple Dosing (Ctrough) of Talazoparib After Multiple Dosing

  Serial blood sample (4 mL) each was collected at predose on Day 27 of Period 1 and Day 20 of Periods 2, predose and 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, and 24 hours postdose on Day 28 of Period 1 and Day 21 of Period 2 to 3, respectively.

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

  Day 1 up to 28 days after last dose of study drug (maximum up to 388 days)

Study Arms (2)

Sequence 1

EXPERIMENTAL

Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days.

Drug: TALZENNA capsule; Drug: Talazoparib soft gel capsule

Sequence 2

EXPERIMENTAL

Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.

Drug: TALZENNA capsule; Drug: Talazoparib soft gel capsule

Interventions

TALZENNA capsule DRUG

Current commercial talazoparib formulation 1 mg once daily given under fasting condition

Sequence 1; Sequence 2

Talazoparib soft gel capsule DRUG

Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition

Sequence 1; Sequence 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological diagnosis of recurrent, locally advanced or metastatic solid tumor that is not amenable for treatment with curative intent.
• Solid tumors with known or likely pathogenic germline or somatic tumor gene defect (eg, one or more BRCA1 or BRCA2 gene defect except for ovarian cancer) that would benefit from PARPi therapy per current approvals for the tumor indication or supported by strong scientific evidence.
• Received at least 1 prior SOC regimen, if it exists, as appropriate for the respective tumor type unless deemed unsuitable or declined these therapies; ovarian cancer participants must have at least 1 prior cytotoxic chemotherapy regimen, including at least 1 course of platinum-based therapy. Participants must not have had disease progression within 6 months of initiation of platinum containing regimen.
• ECOG performance score of 0-1.
• Adequate bone marrow function:
• ANC ≥1500 cells/mm3
• Platelets ≥100,000 cells/mm3
• Hemoglobin ≥10.0 g/dL
• Adequate organ functions:
• CLCR ≥60 mL/min and no documented CLCR \<60 mL/min and no change in CLCR \>25% in the past 4 weeks
• AST and ALT ≤2.5 × ULN; if liver function abnormalities are due to hepatic metastasis, then AST and ALT ≤5 × ULN;
• Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert's syndrome);

You may not qualify if:

• For ovarian participants: Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors.
• Toxicities from previous anti-cancer therapies must be resolved to NCI CTCAE \<Grade 2, except for alopecia, sensory neuropathies ≤Grade 2, or other Grade ≤2 AEs not constituting a safety risk, based on investigator's judgment, are acceptable.
• Diagnosed with MDS or AML.
• Active infection requiring systemic therapy within 2 weeks of enrollment.
• Any condition in which active bleeding or pathological conditions may carry a high risk of bleeding (eg, known bleeding disorder, coagulopathy or tumor involvement with major vessels).
• Known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment. Asymptomatic brain metastases currently not undergoing treatment are allowed.
• Known history of testing positive for HIV, AIDS, positive HBV surface antigen, positive HCV RNA, or positive COVID-19 viral test. Asymptomatic patients with no active infection detected but positive antibody tests, indicating past infection, are allowed.
• Current or anticipated use of P-gp inhibitors, BCRP inhibitors, and P-gp inducers within 2 weeks or 5 half-lives prior to randomization (whichever is longer) .

Sponsors & Collaborators

• Pfizer: lead

Study Sites (31)

California Cancer Associates for Research and Excellence, Inc (cCARE)

Encinitas, California, 92024, United States

Location

Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

California Cancer Associates for Research and Excellence, Inc (cCARE)

San Marcos, California, 92069, United States

Location

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06510, United States

Location

Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Smilow Cancer Hospital Phase 1 Unit

New Haven, Connecticut, 06511, United States

Location

Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

Location

Alliance for Multispecialty Research, LLC

Kansas City, Missouri, 64114, United States

Location

NYU Langone Hospital - Long Island Oncology

Mineola, New York, 11501, United States

Location

NYU Langone Hospital - Long Island

Mineola, New York, 11501, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

NYU Investigational Pharmacy

New York, New York, 10016, United States

Location

NYU Langone Medical Center (Tisch Hospital)

New York, New York, 10016, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

University of Cincinnati Medical Center

Cincinnati, Ohio, 45219, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

West Chester Hospital

West Chester, Ohio, 45069, United States

Location

UPCI Investigational Drug Service

Pittsburgh, Pennsylvania, 15232, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Upmc Shadyside

Pittsburgh, Pennsylvania, 15232, United States

Location

Mary Crowley Cancer Research - Medical City Hospital

Dallas, Texas, 75230, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Liverpool Cancer Therapy Centre

Liverpool, New South Wales, 2170, Australia

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Epworth Healthcare (Epworth Freemasons Hospital)

East Melbourne, Victoria, 3002, Australia

Location

Epworth Healthcare

East Melbourne, Victoria, 3002, Australia

Location

Epworth Healthcare

Richmond, Victoria, 3121, Australia

Location

Epworth Richmond Hospital (Epworth Healthcare)

Richmond, Victoria, 3121, Australia

Location

Epworth Healthcare

East Melbourne, 3002, Australia

Location

Related Publications (1)

• Wang D, Guo CC, Gao X, Wang Y, Yu Y, Plotka A, Elmeliegy M, Shi H, Johnson S, DeAnnuntis L, Hoffman J. Talazoparib Formulation Bridging in Cancer Patients-Challenges and the Critical Role of Model-Informed Drug Development in Approval Despite Failed Bioequivalence. CPT Pharmacometrics Syst Pharmacol. 2025 Dec 11. doi: 10.1002/psp4.70157. Online ahead of print.

  PMID: 41379622 DERIVED

Related Links

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

MeSH Terms

Conditions

Ovarian Neoplasms; Breast Neoplasms; Prostatic Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms

Interventions

talazoparib

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Results Point of Contact

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

ClinicalTrials.gov_inquires@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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be randomly assigned to 1 of 2 sequences to receive Treatment A, B and C in different order as shown below. The first 2 periods will be for BE assessment, with the first period being 28 days and the following periods being 21 days. Period 3 will be a 21 day period to evaluate the food effect on the PK of the proposed talazoparib soft gel capsule formulation that will be included in the fixed sequence after the 2 BE assessment periods (for participants who can tolerate one high-fat/high-calorie meal). Participants must have received 21 consecutive days of continuous 1mg QD drug administration to be considered as completers of a treatment period, before moving on to the next scheduled treatment.

Study Record Dates

• First Submitted: November 13, 2020
• First Posted: December 17, 2020
• Study Start: December 21, 2020
• Primary Completion: February 4, 2022
• Study Completion: July 22, 2022
• Last Updated: September 25, 2024
• Results First Posted: September 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (23); AU (8)