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

NCT ID: NCT05619016

Last Updated: 2022-11-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-23

Study Completion Date

2025-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Esophageal Neoplasms Gastric Neoplasms Malignant Breast Cancer HER2-positive Gastric Cancer

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

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.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Treating clinicians will be blinded for the results of the HER2-PET

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Patients with HER2 positive GEAC or HER2 low cancer (pilot)

The 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.

Group Type EXPERIMENTAL

[68Ga]Ga-ABY-025 PET

Intervention Type DIAGNOSTIC_TEST

\[68Ga\]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 expression

Intervention Type DIAGNOSTIC_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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

[68Ga]Ga-ABY-025 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.

Intervention Type DIAGNOSTIC_TEST

Biopsy and analysis of HER2 expression

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.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

HER2 PET

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Age ≥18 years.
2. The subject has given written consent to participate in the study.
3. 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.
4. At least one metastatic lesion ≥ 10 mm is available for biopsy defined on CT.
5. At least one (and up to five) additional metastatic index lesion/s ≥ 10 mm for evaluation of treatment effect
6. World Health Organization (WHO) performance status ≤ 2.
7. Expected survival \> 12 weeks.

Exclusion Criteria

1. Significantly impaired renal function (GFR \<30 ml/min/1.73 m2)
2. Allergy to iodinated contrast media
3. Subjects that for some reason are unable to exercise their rights, such as cognitive function impairment.
4. Other manifest malignancy except for basal cell carcinoma of the skin.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Karolinska University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Rimma Axelsson

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Rimma Axelsson, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

Karolinska University Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Department of Radiation Physics and Nuclear Medicine, Karolinska University Hospital

Stockholm, , Sweden

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Sweden

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Rimma Axelsson, Prof., MD

Role: CONTACT

+46 8 585 800 00

Siri af Burén, MD

Role: CONTACT

+46739099570

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Rimma Axelsson, Prof

Role: primary

+46858580000

Siri af Burén, MD

Role: backup

+46739099570

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 30911434 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32201920 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20554729 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26912439 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24665085 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26877784 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20130858 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28261749 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37991639 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2022-500448-39-00

Identifier Type: OTHER

Identifier Source: secondary_id

K 2020-9716

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Testing a New Imaging Agent to Identify Cancer
NCT04692831 ACTIVE_NOT_RECRUITING PHASE1
Clinical Value of 89Zr-trastuzumab PET
NCT01832051 COMPLETED PHASE2
HER2-PET Imaging in HER2-low Breast Cancers
NCT06732336 RECRUITING PHASE1/PHASE2
99mTc-ABH2 SPECT/CT in Breast Cancer
NCT06194565 RECRUITING NA