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Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
HER2-targeted PET-imaging with [68Ga]Ga-ABY-025 to predict targeted-therapy response in HER2-expressing metastatic
Renske Altena1, Oscar P B Wiklander2,3, Nour Susaeg Romdhani1
1Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Background:
Trastuzumab deruxtecan (T-DXd) is effective in HER2-expressing metastatic breast cancer (mBC), yet inter-patient benefit varies. The current reference biomarker-HER2 immunohistochemistry (IHC) on tumor biopsies-is insufficient as a sole predictor of response. HER2-targeted PET/CT offers non-invasive, whole-body, real-time assessment of target expression. We hypothesize that HER2-targeted PET with [68Ga]Ga-ABY-025 improves prediction of T-DXd outcomes and supports individualized treatment planning.
Methods:
HER2-Ex PET is a multicenter, phase II open-label diagnostic trial enrolling patients with HER2-low mBC who are candidates for T-DXd under current approvals (EU CT 2024-512721-89-00; NCT06830382). All participants undergo baseline HER2-PET with [68Ga]Ga-ABY-025 and a tumor biopsy. Patients with biopsy-confirmed HER2 expression (IHC 1-2+; Cohort 1) receive T-DXd and repeat HER2-PET after 3-4 cycles; others receive physician's-choice systemic therapy (Cohort 2). The primary endpoint is the association between baseline HER2-PET signal-defined as the mean SUVmax across the five most avid lesions-and objective response per RECIST v1.1 after 3-4 cycles of T-DXd. A total sample size of 70 provides 80% power (α=0.05), allowing for attrition and technical failures. Secondary endpoints include health-economic outcomes and translational analyses of tumor biology and heterogeneity. The study is open at Karolinska University Hospital (Stockholm, Sweden), with Uppsala and Skåne University Hospitals planned for activation in Q1 2026.
Discussion:
Demonstrating a robust correlation between HER2-PET signal and early radiologic response would validate imaging-based patient selection for T-DXd, facilitate adaptive treatment decisions, and enhance biological understanding of intra- and inter-patient HER2 heterogeneity. Key considerations include standardization of imaging protocols across sites, potential temporal discordance between biopsy and imaging, and the non-randomized design. Positive results would justify incorporation of HER2-targeted PET into clinical pathways and inform the design of subsequent randomized trials testing PET-guided T-DXd strategies.
Clinical Trial Registration:
https://clinicaltrials.gov/study/NCT06830382, identifier NCT06830382.
Insights
HER2-targeted PET/CT with [68Ga]Ga-ABY-025 shows promise in predicting treatment response to trastuzumab deruxtecan (T-DXd) in metastatic breast cancer. This imaging approach may improve patient selection for T-DXd therapy.
Area of Science:
- Oncology
- Radiology
- Nuclear Medicine
Background:
- Trastuzumab deruxtecan (T-DXd) is effective for HER2-expressing metastatic breast cancer (mBC), but patient response varies.
- HER2 immunohistochemistry (IHC) on tumor biopsies is an insufficient predictor of T-DXd response.
- HER2-targeted PET/CT offers a non-invasive, whole-body assessment of HER2 expression.
Purpose of the Study:
- To evaluate if HER2-targeted PET with [68Ga]Ga-ABY-025 can improve prediction of T-DXd outcomes in mBC.
- To support individualized treatment planning for T-DXd therapy.
- To assess the correlation between baseline HER2-PET signal and objective response to T-DXd.
Main Methods:
- A multicenter, phase II, open-label diagnostic trial (HER2-Ex PET) enrolling HER2-low mBC patients eligible for T-DXd.
- All participants undergo baseline HER2-PET with [68Ga]Ga-ABY-025 and tumor biopsy.
- Primary endpoint: association between baseline HER2-PET signal (mean SUVmax of five most avid lesions) and objective response (RECIST v1.1) after 3-4 cycles of T-DXd.
Main Results:
- The study aims to enroll 70 patients to provide 80% power for the primary endpoint.
- Secondary endpoints include health-economic outcomes and translational analyses of tumor biology.
- The study is currently open at Karolinska University Hospital, with more sites planned.
Conclusions:
- Validating HER2-PET's correlation with radiologic response could enable imaging-based patient selection for T-DXd.
- Positive results may justify incorporating HER2-targeted PET into clinical pathways for mBC.
- This approach could enhance understanding of HER2 heterogeneity and inform future trial designs.
