[18F]FTT Positron Emission Tomography for the Measurement of PARP Tumor Expression in Patients With Metastatic Breast Cancer

OUTLINE: Patients are assigned to 1 of 2 arms.

Arm I: Patients receive [18F]FTT intravenously (IV) and undergo PET scan 60-75 minutes later on day 1 of initiating SOC PARP inhibitor ± ICI therapy and again at 12 weeks. At least 1-7 days later, patients undergo SOC FDG PET/computed tomography (CT) and follow up scans at 12 weeks and 6 months. Patients may also undergo tissue biopsy during screening and during follow up.

Arm II: Patients receive [18F]FTT IV and undergo PET scan 60-75 minutes later on day 1 of initiating SOC PARP inhibitor ± ICI therapy. At least 1-7 days later, patients undergo SOC FDG PET/CT and follow up scans at 12 weeks and 6 months. Patients may also undergo tissue biopsy during screening.

After initial [18F]FTT PET imaging, patients are followed-up to 6 months or until disease progression.

Inclusion criteria

• Patients must have histologically confirmed invasive breast cancer with metastatic disease
• Patients must be candidates for treatment with PARP inhibitor as a single agent or for PARP inhibitor in combination with an ICI per treating physician discretion
• Patients must have evaluable disease or at least one measurable lesion that can be assessed at baseline by CT (or magnetic resonance imaging [MRI]) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Age >= 18 years
• Karnofsky performance status (KPS) >= 50% or Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Archival tissue (formalin-fixed paraffin-embedded [FFPE]) from at least one metastatic site biopsy should be available prior to study enrollment; if archival tissue is not available, then a metastatic site biopsy will be required during the study screening period
• Patient must be willing to proceed with an on-treatment biopsy of metastatic site if an on-treatment [18F]FTT PET will be performed (at 12 ± 4 weeks after starting PARP inhibitor ± ICI treatment)
• For women of childbearing potential, a negative serum pregnancy test is required within 7 days prior to [18F]FTT PET imaging on day 1. For women who obtain on-treatment (12-week) [18F]FTT imaging, a negative serum pregnancy test will be required within 7 days prior to [18F]FTT PET imaging
• Men and women of reproductive potential need to agree to employ two highly effective and acceptable forms of contraception throughout their participation in the study
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
• Ability to understand and the willingness to sign a written informed consent document. Informed consent must be provided prior to any study specific procedures

Exclusion criteria

• Patients with prior myelodysplastic syndrome or acute myeloid leukemia due to rare risk associated with PARP inhibitor therapy
• Pregnant or breastfeeding women
• Patient with a known hypersensitivity to the proposed PARP inhibitor product
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of PARP inhibitor therapy (per investigator's discretion)