Imaging PD-L1 in Metastatic Triple-Negative Breast Cancer with 89Zr-atezolizumab
Molecular PD-L1 PET/CT Imaging With 89Zr-atezolizumab to Monitor Immune Responses in Metastatic Triple Negative Breast Cancer
This study is testing a new imaging method to see if it can help identify which patients with metastatic triple-negative breast cancer are most likely to benefit from a specific immune therapy.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 64 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Karolinska University Hospital Academic / other |
| Drugs / interventions | atezolizumab, chemotherapy, Radiation, methotrexate, cyclophosphamide, prednisone |
| Locations | 1 site (Stockholm) |
| Trial ID | NCT05742269 on ClinicalTrials.gov |
What this trial studies
This study aims to enhance precision medicine by utilizing 89Zr-atezolizumab PET/CT imaging to visualize PD-L1 expression in patients with metastatic triple-negative breast cancer (mTNBC). By comparing this imaging technique to traditional immunohistochemistry (IHC) methods, the study seeks to identify patients who are most likely to benefit from immune checkpoint inhibitor therapy. Patients scheduled for first-line palliative treatment with nab-paclitaxel and carboplatin will be included, and those with PD-L1 positive tumors will receive atezolizumab. The study is conducted at Karolinska University Hospital, where the radiotracer will be synthesized under Good Manufacturing Practice conditions.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with metastatic triple-negative breast cancer who have measurable disease and are fit for systemic therapy.
Not a fit: Patients who have previously received chemotherapy or targeted therapy for metastatic triple-negative breast cancer may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could lead to more accurate patient selection for immune checkpoint inhibitor therapy, improving treatment outcomes for those with mTNBC.
How similar studies have performed: While the use of PET imaging in this context is innovative, similar studies have shown promise in utilizing advanced imaging techniques for biomarker visualization.
Eligibility criteria
Show full inclusion / exclusion criteria
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 biopsy * Measurable disease according to RECIST v1.1 * At least one metastatic lesion accessible for biopsy * Deemed by treating physician as fit for systemic therapy according to study protocol * ECOG performance score 0/1 * Age ≥ 18 years old * Adequate blood tests for bone marrow, renal and hepatic functions * Able and willing to provide written informed consent Exclusion Criteria: * Previous treatment with chemotherapy or targeted therapy for mTNBC. Radiation therapy and previous chemotherapy (including taxanes) in the context of curative therapy is allowed. * Contraindications for PET/CT as defined for clinical practice * Other malignancy diagnosed within the last five years, except for radically treated basal or squamous cell carcinoma of the skin or CIS of the cervix * Patients 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 lactation * Uncontrolled 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 glomerulonephritis * Patients 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 treatment * A 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 trial * Patients who have received acute, low-dose, systemic immunosuppressant medications (e.g., a one-time dose of dexamethasone for nausea) may be enrolled in the study * Patients 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
Where this trial is running
Stockholm
- Karolinska University Hospital — Stockholm, Sweden (Recruiting)
Study contacts
- Principal investigator: Renske Altena, MD PhD — Karolinska Institutet
- Study coordinator: Renske Altena, MD PhD
- Email: renske.altena@ki.se
- Phone: +46812375518
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.