Using HER2-PET imaging to guide HER2-ADC treatment in metastatic HER2-expressing breast cancer
A Multicentre, Prospective, Open-label Study With [68Ga]Ga-ABY-025 PET-imaging to Characterize HER2-expression and Explore the Therapy-predictive Value for HER2-antibody Drug Conjugates in Patients With Metastatic Breast Cancer
This trial will test whether HER2-targeted PET imaging can help find people with metastatic HER2-expressing breast cancer who should get the HER2-directed antibody‑drug conjugate T‑DXd.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 70 (estimated) |
| Ages | 18 Years and up |
| Sex | Female |
| Sponsor | Karolinska University Hospital Academic / other |
| Drugs / interventions | trastuzumab, chemotherapy |
| Locations | 1 site (Solna) |
| Trial ID | NCT06830382 on ClinicalTrials.gov |
What this trial studies
This is a prospective, multi-center, open-label, exploratory diagnostic phase II imaging trial using the HER2-specific PET tracer [68Ga]Ga-ABY-025. Participants undergo a baseline HER2-PET scan and a tumour biopsy, and treatment allocation is determined by HER2 status on PET and biopsy. Patients with HER2-expressing lesions on biopsy (fresh or archived) will be treated with the antibody‑drug conjugate T‑DXd. The study tests whether PET-guided selection improves identification of patients likely to benefit from T‑DXd, aiming to improve responses and reduce unnecessary toxicity.
Who should consider this trial
Good fit: Female adults with metastatic or locally advanced breast cancer who progressed after at least one line of palliative chemotherapy (or relapsed within six months after adjuvant chemo), able to consent, with at least one lesion ≥10 mm available for biopsy and another lesion ≥10 mm for response assessment, WHO performance status ≤2 and expected survival >12 weeks.
Not a fit: Patients whose tumours are HER2-negative on both PET and biopsy, those unable to undergo required PET or biopsy procedures, or those with very poor performance status or short expected survival are unlikely to benefit from the imaging-guided T-DXd pathway.
Why it matters
Potential benefit: If successful, this approach could better match patients to T-DXd treatment, potentially improving response rates and reducing exposure to ineffective therapy.
How similar studies have performed: Prior studies have shown HER2-targeted PET tracers can detect heterogeneous HER2 expression and clinical trials have shown T‑DXd benefits in HER2-low disease, but using [68Ga]Ga-ABY-025 PET specifically to direct T‑DXd treatment remains exploratory.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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 o Exception can be made when a recent biopsy is available (no more than 12 months old and without exposition to HER2-targeted therapy or local radiotherapy to the specific lesion). * At least one additional metastatic index lesion ≥ 10 mm for evaluation of treatment effect (according to RECIST v1.1) * WHO performance status ≤ 2. * Expected survival \> 12 weeks. * Contraceptives: Females of child-bearing potential must agree to use adequate contraception prior to study entry, for the duration of the study treatment phase and for six months after the last dose of \[68Ga\]Ga-ABY-025. 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. Should a female become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately. If a female participant is of child-bearing potential (females are considered not of childbearing potential if they are at least one year postmenopausal and/or surgically sterile), she must have a documented negative serum Pregnancy testing prior to each administration of the IMP is obligatory. Exclusion Criteria: * 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 * Patients with increased risk of complications from biopsies, i.e. increased risk of bleeding, defined as * prothrombin time test (INR value) \>1.4, platelet count \<70 (109/l), activated partial thromboplastin time (APTT) \>30s. * known bleeding disorders such as haemophilia, von Willebrand disease or platelet disorders. * any anticoagulants or antiplatelet treatment that cannot be temporarily paused
Where this trial is running
Solna
- Karolinska University hospital — Solna, Sweden (Recruiting)
Study contacts
- Study coordinator: Thuy Tran, Associate Prof, PharmD, PhD
- Email: thuy.tran@regionstockholm.se
- Phone: +46812377777
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.