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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Solid Tumors, Solid Tumors, Ovarian Cancer, Breast Cancer, Prostate Cancer, NSCLC, Pancreatic Cancer, Colorectal Cancer

Intervention / Treatment
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* Drug: TALZENNA capsule
* Drug: Talazoparib soft gel capsule
* Drug: Talazoparib soft gel capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 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); Exclusion Criteria 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) .

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional 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)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PARP inhibitor, Talazoparib, Talzenna, BRCA mutation, ATM mutation, Pharmacokinetics, Bioequivalence, Bioavailability, Food effect