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).
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.
Study Type
INTERVENTIONAL
Allocation
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.
OLV Aalst
Aalst, East-Flanders, Belgium
RECRUITINGAZ Delta CHIREC
Brussels, Belgium
RECRUITINGCliniques Universitaires Saint-Luc
Brussels, Belgium
positive, negative, and overall diagnostic agreement between 68Ga-ABS011 PET/CT and the standard of care IHC (and ISH) HER2 status test.
Evaluation, on a per-lesion level, of the diagnostic performance (positive, negative, and overall diagnostic agreement compiled of ratios between true positive, true negative, false psoitive and false negative 68Ga-ABS011 PET/CT results)) of 68Ga-ABS011 PET/CT(III) compared to HER2 IHC (and ISH) status.
Time frame: immediately after the 68Ga-ABS011 PET/CT procedure
Safety of 68Ga-ABS011.
Incidence rate of all adverse events (AEs) and serious AEs (SAEs)
Time frame: up to 6 weeks after initiation of the HER2 targeted monotherapy
Change in treatment management
Proportion of patients for whom the whole body 68Ga-ABS011 PET/CT guided biopsy impacted the management of the mBC
Time frame: immediately after the 68Ga-ABS011 PET/CT procedure
reliability of whole body 68Ga-ABS011 PET/CT compared to HER2-targeted treatment response (Early tumor shrinkage)
Positive and negative predictive value and likelihood ratio of 68Ga-ABS011 using 18F-FDG PET/ceCT as a reference.
Time frame: 6 weeks after initiation of the HER2 targeted monotherapy
reliability of whole body 68Ga-ABS011 PET/CT compared to HER2-targeted treatment response (metabolic response)
Positive and negative predictive value and likelihood ratio of 68Ga-ABS011 using 18F-FDG PET/ceCT as a reference.
Time frame: 6 weeks after initiation of the HER2 targeted monotherapy
Tumor heterogeneity
Inter-tumor heterogeneity assessment by measuring the proportion of discordance between the total number of lesions and number of overlapping lesions confirmed on 18F-FDG and/or 68Ga-ABS011 PET/CT.
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NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
60
Free University Brussels (VUB)
Brussels, Belgium
RECRUITINGInstitut Jules Bordet
Brussels, Belgium
RECRUITINGUniversity Hospital Gasthuisberg
Leuven, Belgium
RECRUITINGTime frame: immediately after the 68Ga-ABS011 PET/CT procedure