About this trial
This is a prospective, multi-center, open-label, exploratory diagnostic phase II imaging trial for patients with metastatic breast cancer with at least one line of systemic therapy.
The overarching aim of the HER2-Ex PET trial is to study the role of precision imaging utilizing positron emission tomography (PET) with the HER2-specific tracer \[68Ga\]Ga-ABY-025 (hereafter referred to as HER2-PET) in enhancing treatment planning for patients with metastatic HER2-expressing breast cancer Patients will be allocated based on HER2-status on PET and biopsy. Patients with HER2-expressing lesions in a fresh or archived tumour biopsy will be treated with T-DXd.
The study hypothesis is that PET/CT precision imaging with a contemporary HER2-radiotracer (\[68Ga\]Ga-ABY-025) can be used and can lead to a potentially better identification of patients who benefit from T-DXd treatment, thereby achieving improved treatment responses as well as fewer side effects. This study's diagnostic approach provides a more individualized treatment strategy. Additionally, this study can potentially give us a better biological understanding of HER2-expressing mBC.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Female patients age ≥18 years.
Metastatic or locally advanced breast cancer with disease progression after ≥ 1 line of chemotherapy in the palliative setting, or with disease relapse within six months after completion of (neo-) adjuvant chemotherapy.
The patient must be able and willing to provide written consent to participate in the study.
At least one metastatic lesion ≥ 10 mm is available for biopsy
Disqualifiers
Contra-indications for treatment for trastuzumab deruxtecan and inability to undergo this treatment as per local treatment routines.
A previously documented metastatic tumor biopsy that was HER2-positive (IHC 3+ and/or HER2 gene amplification).
Other manifest malignancies except for basal cell carcinoma of the skin.
Inadequate cardiac, renal, bone marrow or liver function
Trial population
Patients with mBC considered for treatment with T-DXd.
Trial design
Cohort
Prospective
Treatments tested in this trial
Positron emission tomografy with [68Ga]Ga-ABY-025
Diagnostic testInvestigational Medicinal product (IMP):\[68Ga\]Ga-ABY-025 (all patients)
Treatment groups
Trial outcomes
Primary outcomes
Therapy-predictive role of HER2-PET for the clinical benefit of treatment with T-DXd in patients with HER2-expressing mBC
The primary endpoint is the correlation between the mean \[68Ga \]Ga-ABY-025 SUVmax in the five most ABY-025 avid lesions at the baseline HER2-PET and treatment response according to RECIST v1.1 after three-four cycles of treatment with T-DXd.
Secondary outcomes
Changes in HER2-status according to [68Ga]Ga-ABY-025 uptake prior to and after 3-4 cycles of treatment with T-DXd
Changes (deltaSUVmax) in HER2-status in up to five target lesions according to \[68Ga \]Ga-ABY-025 uptake prior to and after 3-4 cycles of treatment with T-DXd.
Correlation between the proportion of HER2-avid metastases in relation to the total burden of disease (lesions ≥10 mm) on CT and treatment response.
Correlation between HER2-expressing total tumor volume (HER2-TTV; defined as proportion of ABY-025 avid lesions in relation to the total tumor volume (TTV, lesions ≥10 mm) defined on CT) at baseline and Overall Response Rate.
Health related quality of life at baseline, the first response evaluation and at disease progression.
Change in patient reported Health-Related Quality of Life (HR-QoL) as measured by the EQ-5D-5L questionnaire from baseline to the first treatment evaluation.
Sponsors and contacts
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Renske Altena
Lead sponsor
Karolinska University Hospital
Sponsor institution
Karolinska Institutet
Collaborator
Affibody
Collaborator