Using PET imaging to assess HER2 status in solid tumors

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

This study is testing a new type of imaging to see if it can better identify patients with certain solid tumors, like gastroesophageal cancers and low HER2 breast cancer, who might benefit from HER2-targeted treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Karolinska University Hospital (Academic / other)
• Locations: 1 site (Stockholm)
• Trial ID: NCT05619016 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial aims to enhance patient selection for HER2-targeted therapies in individuals with solid tumors, specifically gastroesophageal cancers and metastatic breast cancer with low HER2 expression. Participants will undergo two sessions of HER2-specific PET imaging using Gallium-68-ABY-025, alongside standard biopsies to evaluate HER2 expression. The imaging results will be compared to biopsy analyses to determine the effectiveness of the PET tracer in identifying suitable candidates for treatment. Follow-up will assess disease progression and survival outcomes over one year.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with HER2-positive gastroesophageal adenocarcinoma or HER2-low metastatic breast cancer.

Not a fit: Patients with tumors that are HER2-negative or those who do not have metastatic disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more accurate identification of patients who would benefit from HER2-targeted therapies, improving treatment outcomes.

How similar studies have performed: Other studies utilizing PET imaging for HER2 status assessment have shown promise, indicating potential for success in this approach.

Eligibility criteria

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).

Where this trial is running

Stockholm

• Department of Radiation Physics and Nuclear Medicine, Karolinska University Hospital — Stockholm, Sweden (Recruiting)

Study contacts

• Principal investigator: Rimma Axelsson, Prof., MD — Karolinska University Hospital
• Study coordinator: Rimma Axelsson, Prof., MD

Conditions Esophageal Neoplasms; Gastric Neoplasms Malignant; Breast Cancer; HER2-positive Gastric Cancer; 68-Ga ABY-025; HER2 PET; PET/CT; Gastroesophageal cancer