Breast Cancer Stage IVNCT06830382
HER2-PET as a Precision Imaging Tool for Treatment With HER2-ADC in HER2-expressing mBC
An observational study of Breast Cancer Stage IV and HER2-low Breast Cancer, run by Renske Altena at 1 site in Sweden.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer Stage IV, HER2-low Breast Cancer, Molecular Imaging
- What is being tested?
- Positron emission tomografy with [68Ga]Ga-ABY-025
- How many people
- 70 participants
- Where
- 1 siteSweden
- Study dates
- 3 Oct 2025to 1 Apr 2032
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Patients with mBC considered for treatment with T-DXd.
Who may be able to join
- 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)
Show all 9Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Renske Altena, Associate Professor, MD PhD contact
Sweden1 site, 1 recruiting
- Recruiting
Karolinska University hospital
Solna, 17176
Oscar Wiklander, MD PhD, 0728449485, oscar.wiklander@regionstockholm.se.se
Renske Altena, MD PhD, renske.altena@ki.se
About this study
Official title: 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 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.
Read the detailed description
The target population of the trial consists of female patients with mBC with known non-HER2-positive tumours or with unknown HER2-status. Patients can be included in the trial at the time of disease progression after at least one line of chemotherapy in the palliative setting, or within six months after completion of adjuvant therapy for primary breast cancer.
Patients will be recruited at the Breast Clinics of the Karolinska Comprehensive Cancer Center in Stockholm, the Uppsala Academic Hospital in Uppsala, and Skåne University hospital in Sweden. Additional study sites may be added during the conduct of the trial and after approval of the regulatory agencies. Patients can be referred for study-related investigations from other sites, but all study-related investigations will be performed at one of the three above-mentioned clinics.
Participants are eligible to participate in the study if they meet all the inclusion and none of the exclusion criteria listed below. Subject eligibility (that participants fulfil all inclusion criteria and do not meet any exclusion criteria) is established by the principal investigator or co- investigator that is involved in clinical care for the patient.
When an eligible patient decides to participate in the study, all screening- and treatment related procedures will be initiated no earlier than after the informed consent form is signed.
All patients will undergo a baseline study-specific HER2-PET and a tumour biopsy, the latter guided by the results from the HER2-PET. Lesions with sonographically feasible access and preferably with ABY-025 tracer uptake SUVmax ≥ 6 will be eligible for biopsy. In case no ABY-025 lesions are present or accessible for biopsy, a non-avid metastatic lesion is recommended for biopsy. For practical reasons, biopsies taken prior to the HER2-PET (no more than three months old and without exposition to systemic anti-cancer therapy or local radiotherapy to the specific lesion) can be used for study purpose.
Patients with HER2-expressing fresh or archived tumour biopsy will be treated with T-DXd.
A second HER2-PET will be done in all patients treated with T-DXd at the moment of treatment response evaluation after 9-12 weeks of treatment with T-DXd. An optional third HER2-PET and tumor biopsy will be done at the moment of disease progression on T-DXd.
- Being tested
- Positron emission tomografy with [68Ga]Ga-ABY-025
- Keywords
- HER2-PET, molecular imaging, precision imaging, HER2-low mBC, metastatic breast cancer, HER2-ADC, ABY-025
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Positron emission tomografy with [68Ga]Ga-ABY-025Diagnostic test
Investigational Medicinal product (IMP):[68Ga]Ga-ABY-025 (all patients)
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: HER2-expressing cohort | Patients are allocated to arm 1 based on HER2-status in the tumor biopsy. Patients in arm 1 are treated - according to approved indications and the current standard of care - with trastuzumab deruxtecan. Patients in arm 1 will undergo a second PET after 3-4 treatment courses (9-12 weeks) and and optional third HER2-PET + tumor biopsy at the moment of disease progression. Receives: Diagnostic Test: Positron emission tomografy with [68Ga]Ga-ABY-025 | |
| Arm 2: HER2-zero cohort | Patients with HER2-zero tumors (according to tumor biopsy) will be followed for possible AE's after the experimental investigation (HER2-PET) during two weeks after the investigation, and will thereafter go off study. Receives: Diagnostic Test: Positron emission tomografy with [68Ga]Ga-ABY-025 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 9-12 weeks (first response evaluation)
Secondary outcomes (3)
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.
Measured: 9-12 weeks (first response evaluation)
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.
Measured: 12 months
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.
Measured: 9-12 weeks (first response evaluation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2025
- Study start3 Oct 2025
- Primary completion1 Apr 2030 (estimated)
- Study completion1 Apr 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer Stage IVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Renske Altena
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet, Affibody
- Responsible party
- Sponsor-investigator, Renske Altena, Karolinska University Hospital
- Investigators
- Renske Altena, MD PhD, Study director, Karolinska Institutet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06830382
- Sponsor's protocol ID
- HER2-Ex PET
- Other IDs
- 2024-512721-89-00
- Status last verified
- Nov 2025
- First submitted
- 11 Feb 2025
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: IPD will be shared upon a reasonable request to the study sponsor representative and study director.
Publications
Altena R, Wiklander OPB, Romdhani NS, Kistner A, Klintman M, Skarping I, Lindman H, Rodriguez VS, Frisell O, Lindgren P, Bratteby K, Jussing E, Feldwisch J, Frejd FY, Cascales HS, Siikanen J, Hindorf C, Tran TA. HER2-targeted PET-imaging with [68Ga]Ga-ABY-025 to predict targeted-therapy response in HER2-expressing metastatic breast cancer: study protocol of a multicenter, prospective, open-label trial. Front Oncol. 2026 Apr 10;16:1812711. doi: 10.3389/fonc.2026.1812711. eCollection 2026.
PubMed 42038396
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06830382
- Acronym / sponsor ID
- HER2-Ex PET
- Keywords
- HER2-PET, molecular imaging, precision imaging, HER2-low mBC, metastatic breast cancer, HER2-ADC, ABY-025
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- Renske AltenaUniversity, hospital or other
- Collaborators
- Karolinska Institutet, Affibody
- Study start
- 3 Oct 2025 (actual)
- Primary completion
- 1 Apr 2030 (estimated)
- Study completion
- 1 Apr 2032 (estimated)
- First posted
- 17 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The target population of the trial consists of female patients with mBC with known non-HER2-positive tumours or with unknown HER2-status. Patients can be included in the trial at the time of disease progression after at least one line of chemotherapy in the palliative setting, or within six months after completion of adjuvant therapy for primary breast cancer.
Patients will be recruited at the Breast Clinics of the Karolinska Comprehensive Cancer Center in Stockholm, the Uppsala Academic Hospital in Uppsala, and Skåne University hospital in Sweden. Additional study sites may be added during the conduct of the trial and after approval of the regulatory agencies. Patients can be referred for study-related investigations from other sites, but all study-related investigations will be performed at one of the three above-mentioned clinics.
Participants are eligible to participate in the study if they meet all the inclusion and none of the exclusion criteria listed below. Subject eligibility (that participants fulfil all inclusion criteria and do not meet any exclusion criteria) is established by the principal investigator or co- investigator that is involved in clinical care for the patient.
When an eligible patient decides to participate in the study, all screening- and treatment related procedures will be initiated no earlier than after the informed consent form is signed.
All patients will undergo a baseline study-specific HER2-PET and a tumour biopsy, the latter guided by the results from the HER2-PET. Lesions with sonographically feasible access and preferably with ABY-025 tracer uptake SUVmax ≥ 6 will be eligible for biopsy. In case no ABY-025 lesions are present or accessible for biopsy, a non-avid metastatic lesion is recommended for biopsy. For practical reasons, biopsies taken prior to the HER2-PET (no more than three months old and without exposition to systemic anti-cancer therapy or local radiotherapy to the specific lesion) can be used for study purpose.
Patients with HER2-expressing fresh or archived tumour biopsy will be treated with T-DXd.
A second HER2-PET will be done in all patients treated with T-DXd at the moment of treatment response evaluation after 9-12 weeks of treatment with T-DXd. An optional third HER2-PET and tumor biopsy will be done at the moment of disease progression on T-DXd.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: HER2-expressing cohort | – | Diagnostic Test: Positron emission tomografy with [68Ga]Ga-ABY-025Patients are allocated to arm 1 based on HER2-status in the tumor biopsy. Patients in arm 1 are treated - according to approved indications and the current standard of care - with trastuzumab deruxtecan. Patients in arm 1 will undergo a second PET after 3-4 treatment courses (9-12 weeks) and and optional third HER2-PET + tumor biopsy at the moment of disease progression. |
| Arm 2: HER2-zero cohort | – | Diagnostic Test: Positron emission tomografy with [68Ga]Ga-ABY-025Patients with HER2-zero tumors (according to tumor biopsy) will be followed for possible AE's after the experimental investigation (HER2-PET) during two weeks after the investigation, and will thereafter go off study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with mBC considered for treatment with T-DXd.
Key inclusion criteria (9 listed)
- 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).
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Positron emission tomografy with [68Ga]Ga-ABY-025Investigational Medicinal product (IMP):[68Ga]Ga-ABY-025 (all patients) | Diagnostic test | Arm 1: HER2-expressing cohort, Arm 2: HER2-zero cohort |
Primary outcome
Therapy-predictive role of HER2-PET for the clinical benefit of treatment with T-DXd in patients with HER2-expressing mBC
Time frame: 9-12 weeks (first response evaluation)
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.
3 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
Time frame: 9-12 weeks (first response evaluation)
Correlation between the proportion of HER2-avid metastases in relation to the total burden of disease (lesions ≥10 mm) on CT and treatment response.
Time frame: 12 months
Health related quality of life at baseline, the first response evaluation and at disease progression.
Time frame: 9-12 weeks (first response evaluation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Derived from this study: PubMed 42038396Altena R, Wiklander OPB, Romdhani NS, Kistner A, Klintman M, Skarping I, Lindman H, Rodriguez VS, Frisell O, Lindgren P, Bratteby K, Jussing E, Feldwisch J, Frejd FY, Cascales HS, Siikanen J, Hindorf C, Tran TA. HER2-targeted PET-imaging with [68Ga]Ga-ABY-025 to predict targeted-therapy response in HER2-expressing metastatic breast cancer: study protocol of a multicenter, prospective, open-label trial. Front Oncol. 2026 Apr 10;16:1812711. doi: 10.3389/fonc.2026.1812711. eCollection 2026.
- Individual participant dataSharing planned: Undecided. IPD will be shared upon a reasonable request to the study sponsor representative and study director.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Renske Altena, Associate Professor, MD PhD contact
Renske Altena, MD PhD study director
Karolinska Institutet
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer Stage IV and HER2-low Breast Cancer, run by Renske Altena at 1 site in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Thuy Tran, Associate Prof, PharmD, PhD (+46812377777, thuy.tran@regionstockholm.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Therapy-predictive role of HER2-PET for the clinical benefit of treatment with T-DXd in patients with HER2-expressing mBC (time frame: 9-12 weeks (first response evaluation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06830382, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.