MC# 20-36 - A Phase I, 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

  • Agent(s): Talazoparib
  • Disease Type(s): Solid Tumors that benefit from PARP inhibitor
  • Phase(s): I
  • Drug Classification(s): Targeted Therapy, Small Molecule
  • Molecular Target(s): PARP

Mechanism of Action

Talazoparib is an orally bioavailable inhibitor of the nuclear enzyme poly (ADP-ribose) polymerase (PARP) with potential antineoplastic activity.  Talazoparib exerts cytotoxic effects by 2 mechanisms: inhibition of PARP catalytic activity and PARP trapping.  Inhibition of PARP catalytic activity prevents PARP-mediated DNA repair of single strand DNA breaks that enhances the accumulation of DNA strand breaks and leads to cell death in tumors.  PARP trapping prevents Talazoparib bound PARP protein complexes from readily dissociating from DNA, thereby inhibiting DNA repair, replication, and transcription, resulting in double strand DNA breaks and consequent cytotoxicity.

Purpose

In this study, the sponsor and investigators want to learn:

  • The effects of food on the soft-gel capsule form of talazoparib
  • If the effects of talazoparib as a soft-gel capsule (study drug 1) are the same as the commercial capsule (study drug 2)
  • How much of the study drug 1 is absorbed into the blood and how fast it is removed
  • How much of the study drug 2 is asbosrbed into the blood and how fast is is removed
Inclusion Criteria
  1. Male or female participants between the ages of 18 (or the minimum country specific age of consent if >18) and 70 years, inclusive, at Visit 1 (Screen 1)
  2. Histological diagnosis of recurrent, locally advanced or metastatic solid tumor that is not amenable for treatment with curative intent
    1. 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.  Gene mutation determined by local assessment and classification using a test of either germline or tumor DNA which was performed in a CAP/CLIA certified (or comparable local or regional certified) laboratory.
    2. 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;
  3. ECOG performance score of 0-1
  4. Adequate organ function, as defined as:
    • ANC ≥1500 cells/mm3
    • Platelets ≥100,000 cells/mm3
    • Hemoglobin ≥10.0 g/dL
    • 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);
  5. Other criteria required by protocol
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=""> </grade>
  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. Other criteria required by protocol

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City

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Re: MC# 20-36