Molecular PD-L1 PET/CT Imaging With 89Zr-atezolizumab in Metastatic Triple Negative Breast Cancer

The overarching purpose of this study is to improve precision medicine through more refined therapy selection for breast cancer patients who are candidates for ICI therapy (monoclonal antibodies targeting the programmed death ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1)). The reference standard biomarker for ICI therapy selection is PD-L1 protein expression measured by immunohistochemistry (IHC). Several disadvantages exist with this method, the most important ones being inter- and intralesional as well as spatial heterogeneity in PD-L1 expression, as well as the need for invasive procedures to obtain material for analysis. The study hypothesis is that Positron Emission Tomography combined with Computed Tomography (PET/CT) imaging with a contemporary radiotracer (89Zr-atezolizumab), visualizing PD-L1 expression in the whole body, could be a better predictive biomarker to select which patients benefit from ICI. The use of PET/CT imaging with new radiotracers enables a non-invasive assessment of the presence of the target of treatment in the whole body and provides the possibility to combine functional information with anatomical details.

Inclusion Criteria:Patients with metastatic triple negative breast cancer (mTNBC), defined by pathological criteria: oestrogen receptor expression <10%, progesterone receptor expression <10%, HER2 negative, on the primary tumour or a metastatic biopsyMeasurable disease according to RECIST v1.1At least one metastatic lesion accessible for biopsyDeemed by treating physician as fit for systemic therapy according to study protocolECOG performance score 0/1Age ≥ 18 years oldAdequate blood tests for bone marrow, renal and hepatic functionsAble and willing to provide written informed consentExclusion Criteria:Previous treatment with chemotherapy or targeted therapy for mTNBC. Radiation therapy and previous chemotherapy (including taxanes) in the context of curative therapy (if treatment was completed ≥12 months before randomization) is allowed.Contraindications for PET/CT as defined for clinical practiceOther malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervixPatients in child-bearing age without adequate contraception. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, established, proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices (IUDs), and copper IUDs. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception. Women must refrain from donating eggs during this same period.Pregnancy or lactationUncontrolled hypertension, heart-, liver-, or kidney-diseases or other medical/psychiatric disorders.History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritisPatients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone are eligible for this study. Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible for this study.Patients with eczema, psoriasis, lichen simplex chronicus or vitiligo with dermatologic manifestations only (e.g., no psoriatic arthritis) are permitted provided that they meet the following conditions: Rash must cover less than 10% of body surface area (BSA); Disease is well controlled at baseline and only requiring low potency topical steroids; No acute exacerbations of underlying condition within the last 12 months (not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids).Vaccination with a live vaccine within 30 days of the first dose of study treatmentA known history of Human Immunodeficiency Virus (HIV) infection, hepatitis B (HBsAg reactive) or hepatitis C (HCV RNA detected) infection or active tuberculosis.Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [TNF] agents) within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trialPatients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the studyPatients with a history of allergic reaction to IV contrast requiring steroid pre-treatment should have baseline and subsequent tumor assessments performed using CT.The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.Hypersensitivity to atezolizumab