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

• ClinicalTrials.gov Identifier: NCT04672460
• Recruitment Status: Completed
• First Posted: December 17, 2020
• Last Update Posted: December 7, 2022
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: November 13, 2020
• First Posted Date: December 17, 2020
• Last Update Posted Date: December 7, 2022
• Actual Study Start Date: December 21, 2020
• Actual Primary Completion Date: February 4, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 11, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 11, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1

Study Design

Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:

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.

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

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

Intervention

• 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

Study Arms

• Experimental: Sequence 1
  Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days.
  Interventions:

  • Drug: TALZENNA capsule
  • Drug: Talazoparib soft gel capsule
  • Drug: Talazoparib soft gel capsule
• Experimental: Sequence 2
  Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days.
  Interventions:

  • Drug: TALZENNA capsule
  • Drug: Talazoparib soft gel capsule
  • Drug: Talazoparib soft gel capsule

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 5, 2022): 73
• Original Estimated Enrollment (submitted: December 11, 2020): 46
• Actual Study Completion Date: July 22, 2022
• Actual Primary Completion Date: February 4, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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) .

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT04672460
• Other Study ID Numbers: C3441037; 2020-006101-35 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No
• 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.

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: August 2022