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

NCT05619016 | Unknown Phase 2

• 2 other identifiers: K 2020-97162022-500448-39-00
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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 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).

Conditions

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

Keywords

68-Ga ABY-025; HER2 PET; PET/CT; Gastroesophageal cancer; Metastatic breast cancer; HER2 low

Outcome Measures

Primary Outcomes (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

  up to 24 months

Secondary Outcomes (6)

• SUV

  up to 24 months

• TBR

  up to 24 months

• Intra-individual heterogeneity of HER2-positivity

  up to 24 months

• Feasibility in HER2low

  up to 24 months

• HER2 positive cancer burden

  up to 24 months

Other Outcomes (6)

• Treatment response 1

  up to 36 months

• Treatment response 2

  up to 36 months

• Comparison between HER2 PET and FDG PET

  up to 24 months

Study Arms (1)

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

EXPERIMENTAL

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.

Diagnostic Test: [68Ga]Ga-ABY-025 PET; Diagnostic Test: Biopsy and analysis of HER2 expression

Interventions

[68Ga]Ga-ABY-025 PET 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.

Also known as: HER2 PET

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

Biopsy and analysis of HER2 expression 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.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• Karolinska University Hospital: lead

Study Sites (1)

Department of Radiation Physics and Nuclear Medicine, Karolinska University Hospital

Stockholm, 14186, Sweden

RECRUITING

Related Publications (9)

• 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.

  PMID: 30911434 BACKGROUND

• 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.

  PMID: 32201920 BACKGROUND

• 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.

  PMID: 20554729 BACKGROUND

• 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.

  PMID: 26912439 BACKGROUND

• 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.

  PMID: 24665085 BACKGROUND

• 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.

  PMID: 26877784 BACKGROUND

• 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.

  PMID: 20130858 BACKGROUND

• 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.

  PMID: 28261749 BACKGROUND

• 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.

  PMID: 37991639 DERIVED

MeSH Terms

Conditions

Esophageal Neoplasms; Breast Neoplasms

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Rimma Axelsson, Prof., MD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rimma Axelsson, Prof., MD

CONTACT

+46 8 585 800 00; rimma.axelsson@ki.se

Siri af Burén, MD

CONTACT

+46739099570; siri.afburen@regionstockholm.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Masking Details: Treating clinicians will be blinded for the results of the HER2-PET
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 16, 2022
• Study Start: November 23, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: November 30, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)