NCT06369831

HER2 Targeted Molecular Imaging in mBC Using 68Ga-ABS011

Evaluating the Diagnostic Performance of Human Epidermal Growth Factor Receptor 2 (HER2) Targeted Positron Emission Tomography and Computed Tomography (PET/CT) With 68Ga-ABS011 in Metastatic Breast Cancer (mBC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Abscint NV/SA · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II study aims to confirm the diagnostic performance and accuracy of 68Ga-ABS011 PET/CT in determining the HER2 expression status, and to evaluate 68Ga-ABS011's ability to drive changes in therapeutic treatment. 68Ga-ABS011 will be compared to the current standard of care (SOCa) diagnostic methods including immunohistochemistry (IHC), in situ hybridization (ISH) and imaging tools used for treatment response follow-up including Fluorodeoxyglucose F-18 (18F-FDG) positron emitted tomography (PET) and contrast enhanced computed tomography (ceCT).

Detailed description

Lesion sampling error resulting tumor heterogeneity is probably the biggest pitfall when determining the HER2 status. Moreover, IHC expression or gene amplification can be affected by procedural differences and sample handling differences that are influenced by the experience and training of the pathologist's team. Last but not least, immunohistochemistry interpretation remains a semiquantitative subjective scoring which is susceptible to considerable interobserver variability. 68Ga-ABS011, is a NOTA (chelating agent to label sdAbs with radionuclides) linked single domain antibody (sdAb) with the capability to bind HER2 tumor antigens very fast, while the unbound fraction is rapidly cleared from the blood. ABS011 is labeled with gallium-68, a short-lived isotope (68Ga, t1/2: 68 min). Combining rapid targeting of HER2, fast clearance and low radiation burden make 68Ga-ABS011 is suited for specific tumor marker whole body PET/CT imaging. The available preclinical and clinical results with 68Ga-ABS011 (or its first generation product), including a phase I and a phase II clinical trials, did not reveal any safety signals. Extended safety assessments, including anti-drug antibody (ADA) serum evaluations after 2 consecutive administrations, supported the previously observed low immunogenicity risk profile with these sdAbs. Besides safety, this tracer showed potential in the assessment of inter-lesional HER2 expression heterogeneity and also displayed some higher sensitive and more specific determination of disease extent compared to 18F-FDG. Whole body mapping of HER2, an antigen present in multiple cancer types, might (I) Reduce tumor lesion sampling errors and resultingly reduce false negative HER2 IHC outcomes, potentially broadening the therapeutic and interventional treatment options for the patient; (II) Enable identification of inter-and intratumor heterogeneity; and (III) Support follow-up of HER2 targeted treatment response, and accompanied treatment decisions.

Conditions

• Metastatic Breast Cancer

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	68Ga-NOTA-ABSCINT-HER2 PET/CT	68Ga-ABS011, is a single domain antibody (sdAb) with the capability to bind HER2 tumor antigens very fast, while the unbound fraction is rapidly cleared from the blood. ABS011 is labeled with gallium-68, a short-lived isotope (68Ga, t1/2: 68 min). Combining rapid targeting of HER2, fast clearance and low radiation burden make 68Ga-ABS011 is suited for specific tumor marker whole body PET/CT imaging.

Timeline

• Start date: 2024-09-12
• Primary completion: 2025-09-01
• Completion: 2025-09-01
• First posted: 2024-04-17
• Last updated: 2025-05-21

Locations

6 sites across 1 country: Belgium