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

NCT05742269 | Terminated

• 1 other identifier: MIMIR-mTNBC
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Triple-Negative Breast Carcinoma

Keywords

89Zr-atezolizumab; PD-L1 PET; predictive biomarker

Outcome Measures

Primary Outcomes (1)

• Level of statistical agreement (Cohen kappa coefficient) between PD-L1 status on IHC (with SP142 Ventana) and PET (with 89Zr-atezolizumab)

  Level of statistical agreement by means of Cohen's kappa coefficient between PD-L1 IHC (positive defined as expression ≥1% on immune cells with SP142) and PD-L1 PET/CT (PD-L1 positivity is defined as having at least one lesion with radiotracer uptake over the background uptake). Level of statistical agreement by means of Cohen's kappa coefficient between PD-L1 IHC (positive defined as expression ≥1% on immune cells with SP142) and PD-L1 PET/CT (PD-L1 positivity is defined as having at least one lesion with radiotracer uptake over the background uptake). Level of statistical agreement by means of Cohen's kappa coefficient between PD-L1 IHC (positive defined as expression ≥1% on immune cells with SP142) and PD-L1 PET/CT (PD-L1 positivity is defined as having at least one lesion with radiotracer uptake over the background uptake).

  baseline

Secondary Outcomes (5)

• Treatment outcomes - response rate

  Baseline - up to one year

• Treatment outcomes - progression free survival

  Baseline - up to one year

• Treatment-related toxicities

  Baseline - up to one year

• Heterogeneity in PD-L1 status

  Baseline

• Improved staging

  Baseline

Other Outcomes (2)

• Immune infiltrate and PD-L1 status

  Baseline

• ICI toxicity prediction

  Baseline - up to one year

Study Arms (2)

PD-L1 positive disease (on PET and/or IHC)

Nab-paclitaxel at a dose of 100 mg per square meter of body-surface area, administered intravenously, on days 1, 8, and 15, and carboplatin at a dose of Area Under the Curve (AUC) 5 on day 1 of every 28-day cycle. The patients with a PD-L1+ tumour, according to IHC with the SP142 antibody (≥ 1% on immune cells) and/or 89Zr-atezolizumab tracer uptake on PET-imaging, will receive atezolizumab at a dose of 840 mg, administered intravenously, on days 1 and 15.

Diagnostic Test: 89Zr-atezolizumab PET/CT

PD-L1 negative disease (on PET and IHC)

Nab-paclitaxel at a dose of 100 mg per square meter of body-surface area, administered intravenously, on days 1, 8, and 15, and carboplatin at a dose of Area Under the Curve (AUC) 5 on day 1 of every 28-day cycle.

Diagnostic Test: 89Zr-atezolizumab PET/CT

Interventions

89Zr-atezolizumab PET/CT DIAGNOSTIC_TEST

All patients undergo a 89Zr-atezolizumab PET/CT. Allocation to chemotherapy + atezolizumab in case of a PD-L1 positive tumor (on IHC and/or PET)

PD-L1 negative disease (on PET and IHC); PD-L1 positive disease (on PET and/or IHC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients with newly diagnosed irresectable or metastatic triple negative breast cancer

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska University Hospital: lead

Study Sites (1)

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Renske Altena, MD PhD

  Karolinska Institutet

  PRINCIPAL INVESTIGATOR

• Jonas Bergh, MD, Prof

  Karolinska Institutet

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 23, 2023
• Study Start: July 1, 2023
• Primary Completion: December 1, 2024
• Study Completion: March 11, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

SE (1)