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

A PHASE 1, OPEN LABEL, CROSSOVER STUDY TO ESTABLISH BIOEQUIVALENCE BETWEEN THE PROPOSED SOFT GEL TALAZOPARIB CAPSULE FORMULATION AND THE CURRENT TALAZOPARIB COMMERCIAL FORMULATION AND TO ESTIMATE THE FOOD EFFECT ON PHARMACOKINETICS OF THE PROPOSED TALAZOPARIB SOFT GEL CAPSULE FORMULATION IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer; NSCLC; Prostate Cancer; Advanced Solid Tumors; Solid Tumors
• Intervention / Treatment: Drug: TALZENNA capsule; Drug: Talazoparib soft gel capsule; Drug: Talazoparib soft gel capsule

• Study Type: Interventional
• Enrollment (Actual): 73
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • East Melbourne, Australia, 3002
    • Epworth Healthcare
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Cancer Therapy Centre
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Health
    • East Melbourne, Victoria, Australia, 3002
      • Epworth Healthcare
    • East Melbourne, Victoria, Australia, 3002
      • Epworth Healthcare (Epworth Freemasons Hospital)
    • Richmond, Victoria, Australia, 3121
      • Epworth Healthcare
    • Richmond, Victoria, Australia, 3121
      • Epworth Richmond Hospital (Epworth Healthcare)
• United States
  • California
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research and Excellence, Inc (cCARE)
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center, Samuel Oschin Comprehensive Cancer Institute
    • San Marcos, California, United States, 92069
      • California Cancer Associates for Research and Excellence, Inc (cCARE)
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Smilow Cancer Hospital at Yale New Haven
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Hospital
    • New Haven, Connecticut, United States, 06511
      • Smilow Cancer Hospital Phase 1 Unit
  • Florida
    • Lake Mary, Florida, United States, 32746
      • Florida Cancer Specialists
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispecialty Research, LLC
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital - Long Island Oncology
    • Mineola, New York, United States, 11501
      • NYU Langone Hospital - Long Island
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • New York, New York, United States, 10016
      • NYU Investigational Pharmacy
    • New York, New York, United States, 10016
      • NYU Langone Medical Center (Tisch Hospital)
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPCI Investigational Drug Service
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research - Medical City Hospital
    • San Antonio, Texas, United States, 78229
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. 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.
2. ECOG performance score of 0-1.

3. Adequate bone marrow function:

   • ANC ≥1500 cells/mm3
   • Platelets ≥100,000 cells/mm3
   • Hemoglobin ≥10.0 g/dL

4. 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);

Exclusion Criteria

1. For ovarian participants: Non-epithelial tumors or ovarian tumors with low malignant potential (ie, borderline tumors) or mucinous tumors.
2. 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.
3. Diagnosed with MDS or AML.
4. Active infection requiring systemic therapy within 2 weeks of enrollment.
5. 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).
6. Known or suspected brain metastasis or active leptomeningeal disease undergoing or requiring treatment. Asymptomatic brain metastases currently not undergoing treatment are allowed.
7. 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.
8. 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) .

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence 1; Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days.	Drug: TALZENNA capsule; Current commercial talazoparib formulation 1 mg once daily given under fasting condition; Drug: Talazoparib soft gel capsule; Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition; Drug: Talazoparib soft gel capsule; Proposed talazoparib soft gel capsule formulation 1 mg once daily under fed condition
Experimental: Sequence 2; Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.	Drug: TALZENNA capsule; Current commercial talazoparib formulation 1 mg once daily given under fasting condition; Drug: Talazoparib soft gel capsule; Proposed talazoparib soft gel capsule formulation 1 mg once daily under fasting condition; Drug: Talazoparib soft gel capsule; Proposed talazoparib soft gel capsule formulation 1 mg once daily under fed condition

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC24 of all talazoparib treatment	Area under the plasma concentration-time curve from time 0 to 24 hours	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Cmax of all talazoparib treatment	Maximum plasma concentration	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tmax of all talazoparib treatment	Time for Cmax	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Ctrough of all talazoparib treatment	Predose plasma drug concentration	24 hours [On Day 27 for Period 1 and on Day 20 for Periods 2]
CL/F of all talazoparib treatment	Apparent clearance after oral dose	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
AUClast of all talazoparib treatment	Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast)	24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3]
Safety and tolerability of the proposed talazoparib soft gel capsule formulation	Incidence of AEs characterized by type, severity (graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study treatment	Approximately 4 years

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2020
• Primary Completion (Actual): February 4, 2022
• Study Completion (Actual): July 22, 2022

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: December 11, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimate): December 7, 2022
• Last Update Submitted That Met QC Criteria: December 5, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: PARP inhibitor; Pharmacokinetics; Bioequivalence; Food effect; Bioavailability; BRCA mutation; Talazoparib; Talzenna; ATM mutation
• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Poly(ADP-ribose) Polymerase Inhibitors; Talazoparib
• Other Study ID Numbers: C3441037; 2020-006101-35 (EudraCT Number)

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes