HER2-PET as a Precision Imaging Tool for Treatment With HER2-ADC in HER2-expressing mBC

NCT06830382 | Recruiting

• 2 other identifiers: HER2-Ex PET2024-512721-89-00
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Breast Cancer Stage IV; HER2-low Breast Cancer; Molecular Imaging

Keywords

HER2-PET; molecular imaging; precision imaging; HER2-low mBC; metastatic breast cancer; HER2-ADC; ABY-025

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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.

  12 months

• Health related quality of life at baseline, the first response evaluation and at disease progression.

  9-12 weeks (first response evaluation)

Study Arms (2)

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.

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.

Diagnostic Test: Positron emission tomografy with [68Ga]Ga-ABY-025

Interventions

Positron emission tomografy with [68Ga]Ga-ABY-025 DIAGNOSTIC_TEST

Investigational Medicinal product (IMP):\[68Ga\]Ga-ABY-025 (all patients)

Arm 1: HER2-expressing cohort; Arm 2: HER2-zero cohort

Eligibility Criteria

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

Study Population

Patients with mBC considered for treatment with T-DXd.

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Renske Altena: lead
• Karolinska Institutet: collaborator
• Affibody: collaborator

Study Sites (1)

Karolinska University hospital

Solna, 17176, Sweden

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood samples for extracellular vesicles; tumor biopsies for proteomics analyses

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Study Officials

• Renske Altena, MD PhD

  Karolinska Institutet

  STUDY DIRECTOR

Central Study Contacts

Thuy Tran, Associate Prof, PharmD, PhD

CONTACT

+46812377777; thuy.tran@regionstockholm.se

Renske Altena, Associate Professor, MD PhD

CONTACT

renske.altena@ki.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Study Director

Study Record Dates

• First Submitted: February 11, 2025
• First Posted: February 17, 2025
• Study Start: October 3, 2025
• Primary Completion (Estimated): April 1, 2030
• Study Completion (Estimated): April 1, 2032
• Last Updated: November 20, 2025

Record last verified: 2025-11

Locations

SE (1)