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Esophageal NeoplasmsPhase 2NCT05619016

[68Ga]Ga-ABY-025 PET for Quantification of HER2-status in Solid Tumors

A Phase 2 study testing [68Ga]Ga-ABY-025 PET and Biopsy and analysis of HER2 expression in people with Esophageal Neoplasms and Gastric Neoplasms Malignant, run by Karolinska University Hospital at 1 site in Sweden.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The goal of this phase II clinical trial is to improve the selection of patients with solid tumors who would benefit from effective treatment with HER2 targeted drugs. This will be achieved by examining patients with HER2 positive tumors in the esophagus or stomach or patients with advanced breast cancer with low HER2… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
[68Ga]Ga-ABY-025 PET and Biopsy and analysis of HER2 expression
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
72 participants
Where
1 siteSweden
Study dates
23 Nov 2022to 31 Dec 2025
Phase
Phase 2
Are there results?
None posted in the registry

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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥18 years.
  • The subject has given written consent to participate in the study.
  • Patients with metastatic disease because of gastroesophageal adenocarcinoma or HER2-low breast cancer. Cohort 1: Histologically confirmed HER2-positive primary gastroesophageal adenocarcinoma, scheduled for palliative HER2-targeted therapy; Cohort 2: HER2-low metastatic breast cancer first within a pilot study (of which five patients with de novo HER2-low mBC and five patients with pre-treated HER2-low mBC). Later, within a post-pilot study. Definition of HER2 positivity (ASCO College of American Pathologist 2018. HER2 Testing for Breast Cancer Guidelines.) HER2-low mBC is defined as IHC 1+ or IHC 2+ but ISH negative.
  • At least one metastatic lesion ≥ 10 mm is available for biopsy defined on CT.
  • At least one (and up to five) additional metastatic index lesion/s ≥ 10 mm for evaluation of treatment effect
  • World Health Organization (WHO) performance status ≤ 2.
  • Expected survival > 12 weeks.

Who cannot join

  • Significantly impaired renal function (GFR <30 ml/min/1.73 m2)
  • Allergy to iodinated contrast media
  • Subjects that for some reason are unable to exercise their rights, such as cognitive function impairment.
  • Other manifest malignancy except for basal cell carcinoma of the skin.
  • The patient presenting any contraindication for the use of HER2 targeted therapy for metastatic disease: congestive heart failure, baseline left ventricular ejection fraction (LVEF) less than 50%, transmural myocardial infarction, uncontrolled hypertension (systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg), angina pectoris requiring medication, clinically significant valvular heart disease, high-risk arrhythmias, lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome, active gastrointestinal bleeding.
  • Inadequate organ function, suggested by the following laboratory results: absolute neutrophil count <1,500 cells/mm3, haemoglobin <90 g/L, total bilirubin ≥1.5 x Upper Limit of Normal (ULN) (unless the patient has documented Gilbert's syndrome), Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or Alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT) >5.0 x ULN.
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  • Positive pregnancy test in women of childbearing potential (premenopausal or <12 months of amenorrhea post-menopause and who have not undergone surgical sterilization), or lactation.
  • Female patients of childbearing potential and sexually active and not willing to use a highly effective contraceptive. Examples of highly effective 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.
  • 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 disorder such as hemophilia, von Willebrand disease or platelet disorders.
  • any anticoagulants or antiplatelet treatment (except for low-dose acetyl-salicylic acid (ASA), i. e 75 mg daily).

Trial locations and contacts

1 site in 1 country.

Rimma Axelsson, Prof., MD contact

+46 8 585 800 00

rimma.axelsson@ki.se

Siri af Burén, MD contact

+46739099570

siri.afburen@regionstockholm.se

Sweden1 site, 1 recruiting

  • Department of Radiation Physics and Nuclear Medicine, Karolinska University Hospital

    Stockholm, 14186

    Rimma Axelsson, Prof, +46858580000, rimma.axelsson@ki.se

    Siri af Burén, MD, +46739099570, siri.afburen@regionstockholm.se

    Recruiting

Other trials in Sweden

About this study

Official title: Phase II Study of [68Ga]Ga-ABY-025 PET for Non-invasive Quantification of HER2-status in Solid Tumors

The goal of this phase II clinical trial is to improve the selection of patients with solid tumors who would benefit from effective treatment with HER2 targeted drugs. This will be achieved by examining patients with HER2 positive tumors in the esophagus or stomach or patients with advanced breast cancer with low HER2 expression (HER2low) with the HER2 specific positron emission tomography (PET) tracer ABY-025 (HER2-PET) and compare the imaging results with HER2 expression in tumor tissue derived from biopsies (reference standard).

Read the detailed description

The goal of this phase II interventional clinical trial is to evaluate the HER2-status in tumor lesions measured by Gallium-68-ABY-025-uptake on PET/CT with HER2-status defined by reference standard (laboratory analyses) in patients with gastroesophageal cancer (GEAC) and metastatic breast cancer with low HER2 expression (HER2-low mBC).

The participants in GEAC cohort of the study will undergo two sessions of HER2 PET and one 18-Fluorodeoxyglucose (18F-FDG) PET/CT for study purposes. The first HER2 PET is performed within 21 days before initiation of the systemic oncological treatment and is followed by tumor biopsies. A second HER2 PET and a second 18F-FDG PET will be performed adjacent to response evaluation after 3 courses of oncological therapy. Data from the PET investigations will be compared to HER2 expression analyses of the biopsy specimen and correlated to disease and survival data at follow up one year after inclusion. Within the pilot study, participants with HER2 low mBC will undergo one HER2 PET followed by biopsies.

Being tested
[68Ga]Ga-ABY-025 PET, Biopsy and analysis of HER2 expression
Keywords
68-Ga ABY-025, HER2 PET, PET/CT, Gastroesophageal cancer, Metastatic breast cancer, HER2 low
Medical subject headings
Esophageal Neoplasms, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • [68Ga]Ga-ABY-025 PETDiagnostic test

    Also called HER2 PET

    [68Ga]Ga-ABY-025 PET: Each patient in Cohort 1 will be imaged with a PET/CT twice using the radiolabeled investigational product ABY-025 as a tracer. At the time of injection, a 45-minutes long dynamic scan will take place over a pre specified region of interest. Three hours after injection a full body PET scan followed by a CT scan will be performed.

  • Biopsy and analysis of HER2 expressionDiagnostic test

    Biopsy: Within 3 days after the first ABY-025-PET a tissue sample from at least one metastasis >10 mm available for biopsy, preferably shallow lymph nodes, will be analyzed for HER2 expression through immunohistochemistry- (IHC) and in situ hybridization- (ISH) analysis in patients with GEAC and HER2low mBC.

Study groups in NCT05619016
Study groupRoleWhat they receive
Patients with HER2 positive GEAC or HER2 low cancer (pilot)ExperimentalThe participants of the study will undergo two sessions of HER2 PET and one 18F-FDG PET/CT for study purposes. The first HER2 PET is performed within 21 days before initiation of the systemic oncological treatment including HER2-targeted drugs, and is followed by tumor biopsies. A second HER2 PET and a second 18F-FDG PET will be performed adjacent to response evaluation after 3 courses of oncological therapy. Data from the PET investigations will be compared to HER2 expression analyses of the biopsy specimen and correlated to disease and survival data at follow up one year after inclusion. Within the pilot study, participants with HER2 low mBC will undergo one HER2 PET followed by biopsies.
Receives: Diagnostic Test: [68Ga]Ga-ABY-025 PET; Diagnostic Test: Biopsy and analysis of HER2 expression

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of HER2-positive lesions

    Percentage of HER2-positive lesions (primary tumors and/or metastases) measured by tracer uptake on PET/CT which are also positive regarding HER2-status defined by reference biopsy-based standard used in clinical routine in patients with GEAC

    Measured: up to 24 months

Secondary outcomes (6)

  1. SUV

    Optimal Standardized Uptake Values (SUVs) cut-off values for separating HER2-positive/or HER2-low from HER2-negative lesions by reference standard methods.

    Measured: up to 24 months

  2. TBR

    Tumor-to-Background Ratio (TBR) cut-off values for separating HER2-positive/or HER2-low from HER2-negative lesions by reference standard methods.

    Measured: up to 24 months

  3. Intra-individual heterogeneity of HER2-positivity

    Percentage of tracer uptake sites on whole-body HER2 PET compared to all known cancer-related lesions, determined on the routine radiological investigation with CT as an estimation of intra-individual heterogeneity of HER2-positivity.

    Measured: up to 24 months

  4. Feasibility in HER2low

    Percentage of false-negative findings on HER2 PET compared to results from immunohistochemistry testing (IHC) from at least one index lesion in patients with HER2-low mBC.

    Measured: up to 24 months

  5. HER2 positive cancer burden

    Percentage of tracer uptake in sites, not previously determined on the routine radiological investigation with CT, as a measure of cancer burden determined on the whole body HER2 PET in tumor lesions.

    Measured: up to 24 months

  6. Safety aspects of ABY-025

    Frequency of Adverse Events (AEs), Adverse Reactions (ARs), Serious Adverse Events (SAEs), and Suspected Unexpected Serious Adverse Reactions (SUSARs).

    Measured: up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2022
  2. Study start23 Nov 2022
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion31 Dec 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Model description
Prospective, single-center, single-blinded, diagnostic explorative phase II basket trial. Investigators select subjects that are scheduled for anti-HER2 treatment due to * metastatic HER2 positive gastroesophageal cancer (GEAC) * metastatic breast cancer with low HER2 expression (HER2low mBC). All patients undergo a PET/CT with the interventional drug/radiotracer 68Ga-ABY-025 before starting treatment. GEAC patients will undergo an additional ABY-025-PET after 3 cycles of treatment. Results will be compared to HER2 analysis of tissue samples.
Masking
None (open label)
Enrolment
72 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05619016
Sponsor's protocol ID
K 2020-9716
Other IDs
2022-500448-39-00
Status last verified
Nov 2022
First submitted
7 Nov 2022
Last updated
30 Nov 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Velikyan I, Schweighofer P, Feldwisch J, Seemann J, Frejd FY, Lindman H, Sorensen J. Diagnostic HER2-binding radiopharmaceutical, [68Ga]Ga-ABY-025, for routine clinical use in breast cancer patients. Am J Nucl Med Mol Imaging. 2019 Feb 15;9(1):12-23. eCollection 2019.

    PubMed 30911434

  • Alhuseinalkhudhur A, Lubberink M, Lindman H, Tolmachev V, Frejd FY, Feldwisch J, Velikyan I, Sorensen J. Kinetic analysis of HER2-binding ABY-025 Affibody molecule using dynamic PET in patients with metastatic breast cancer. EJNMMI Res. 2020 Mar 23;10(1):21. doi: 10.1186/s13550-020-0603-9.

    PubMed 32201920

  • Ahlgren S, Orlova A, Wallberg H, Hansson M, Sandstrom M, Lewsley R, Wennborg A, Abrahmsen L, Tolmachev V, Feldwisch J. Targeting of HER2-expressing tumors using 111In-ABY-025, a second-generation affibody molecule with a fundamentally reengineered scaffold. J Nucl Med. 2010 Jul;51(7):1131-8. doi: 10.2967/jnumed.109.073346. Epub 2010 Jun 16.

    PubMed 20554729

  • Sandstrom M, Lindskog K, Velikyan I, Wennborg A, Feldwisch J, Sandberg D, Tolmachev V, Orlova A, Sorensen J, Carlsson J, Lindman H, Lubberink M. Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients. J Nucl Med. 2016 Jun;57(6):867-71. doi: 10.2967/jnumed.115.169342. Epub 2016 Feb 9.

    PubMed 26912439

  • Sorensen J, Sandberg D, Sandstrom M, Wennborg A, Feldwisch J, Tolmachev V, Astrom G, Lubberink M, Garske-Roman U, Carlsson J, Lindman H. First-in-human molecular imaging of HER2 expression in breast cancer metastases using the 111In-ABY-025 affibody molecule. J Nucl Med. 2014 May;55(5):730-5. doi: 10.2967/jnumed.113.131243. Epub 2014 Mar 24.

    PubMed 24665085

  • Sorensen J, Velikyan I, Sandberg D, Wennborg A, Feldwisch J, Tolmachev V, Orlova A, Sandstrom M, Lubberink M, Olofsson H, Carlsson J, Lindman H. Measuring HER2-Receptor Expression In Metastatic Breast Cancer Using [68Ga]ABY-025 Affibody PET/CT. Theranostics. 2016 Jan 1;6(2):262-71. doi: 10.7150/thno.13502. eCollection 2016.

    PubMed 26877784

  • Tolmachev V, Velikyan I, Sandstrom M, Orlova A. A HER2-binding Affibody molecule labelled with 68Ga for PET imaging: direct in vivo comparison with the 111In-labelled analogue. Eur J Nucl Med Mol Imaging. 2010 Jul;37(7):1356-67. doi: 10.1007/s00259-009-1367-7. Epub 2010 Feb 4.

    PubMed 20130858

  • Sandberg D, Tolmachev V, Velikyan I, Olofsson H, Wennborg A, Feldwisch J, Carlsson J, Lindman H, Sorensen J. Intra-image referencing for simplified assessment of HER2-expression in breast cancer metastases using the Affibody molecule ABY-025 with PET and SPECT. Eur J Nucl Med Mol Imaging. 2017 Aug;44(8):1337-1346. doi: 10.1007/s00259-017-3650-3. Epub 2017 Mar 6.

    PubMed 28261749

  • Altena R, Buren SA, Blomgren A, Karlsson E, Tzortzakakis A, Brun N, Moein MM, Jussing E, Frejd FY, Bergh J, Tran TA, Hartman J, Axelsson R. Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [68Ga]Ga-ABY-025: Results from a Pilot Study. J Nucl Med. 2024 May 1;65(5):700-707. doi: 10.2967/jnumed.123.266847.

    PubMed 38548353

  • Jussing E, Ferrat M, Moein MM, Alfredeen H, Tegnebratt T, Bratteby K, Samen E, Feldwisch J, Altena R, Axelsson R, Tran TA. Optimized, automated and cGMP-compliant synthesis of the HER2 targeting [68Ga]Ga-ABY-025 tracer. EJNMMI Radiopharm Chem. 2023 Nov 22;8(1):41. doi: 10.1186/s41181-023-00226-y.

    PubMed 37991639

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing [68Ga]Ga-ABY-025 PET and Biopsy and analysis of HER2 expression in people with Esophageal Neoplasms and Gastric Neoplasms Malignant, run by Karolinska University Hospital 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 7 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 30 Nov 2022. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Rimma Axelsson, Prof., MD (+46 8 585 800 00, rimma.axelsson@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of HER2-positive lesions (time frame: up to 24 months). 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 NCT05619016, which also lists 10 linked publications.

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 30 Nov 2022.

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