Trial Title:
HER2 Targeted Molecular Imaging in MBC Using 68Ga-ABS011
NCT ID:
NCT06369831
Condition:
Metastatic Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Conditions: Keywords:
radiolabeled
single domain antibody
68Ga
Gallium-68
HER2
PET/CT
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
Interventional, Phase IIb, prospective, single arm radio-diagnostic study.
Driven by number of biopsied lesions (and not by number of patients)
Primary purpose:
Diagnostic
Masking:
None (Open Label)
Intervention:
Intervention type:
Diagnostic Test
Intervention name:
68Ga-NOTA-ABSCINT-HER2 PET/CT
Description:
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.
Arm group label:
68Ga-ABS011 PET/CT
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Adult (≥ 18 years at the time of informed consent signature) male or female patient
2. Patient with confirmed de novo or pre-treated mBC (multiple previous treatment lines
in metastatic setting are allowed).
3. Patients with documented hormone receptor positive/HER2 negative, triple-negative or
HER2 positive mBC that could become eligible for commercially available HER2
targeted monotherapy (i.e. through confirmation of HER2 IHC non-0 status assessed
during the course of the study).
4. Patient presenting with at least one target biopsiable, FDG positive , non-liver
metastatic lesion of ≥15 mm defined on ceCT (as part of screening 18F-FDG PET/ceCT
assessment).
5. Patient willing to undergo at least one tumor biopsy.
6. Male patients able to father children and female patients of childbearing potential
agree to use effective methods of contraception during the diagnostic and SOCa
treatment follow-up study phases.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2.
8. Ability and willingness of the research participant to provide written informed
consent.
Exclusion Criteria:
1. Primary (non-metastatic) breast cancer.
2. Patient not willing to undergo at least one tumor biopsy. Note: A recent biopsy and
accompanied locally assessed IHC/ISH analyses, completed before screening, will not
be accepted for study purposes.
3. 18F-FDG PET/ceCT completed before screening and patient not willing to repeat this
assessment.
4. Metastatic setting 18F-FDG PET/ceCT indicating that the identified tumor lesions
cannot be biopsied due their location and/or tissue type and/or an increased risk
for serious comorbidities.
5. Brain and liver metastases are the sole sites of metastatic disease.
6. Life expectancy lower than 3 months.
7. Pregnancy or breastfeeding.
8. Inadequate organ function, suggested by clinically relevant abnormal laboratory
results:
1. Significantly impaired renal function defined as estimated Glomerular
Filtration Rate (GFR) <30 ml/min/1.73m2.
2. Absolute neutrophil count <1,500 cells/mm3.
3. Total bilirubin ~1.5 x Upper Limit of Normal (ULN) (unless the patient has
documented Gilbert's syndrome).
4. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT)
or Alanine aminotransferase (ALT)/ serum glutamic pyruvic transaminase (SGPT)
>5.0 x ULN.
9. Patients with a known hypersensitivity to any of the investigational medicinal
product (IMP) components or packaging.
10. Patients with increased risks of bleeding or other complications from biopsies (e.g.
patients under anticoagulation therapy for whom temporary discontinuation of this
therapy cannot be safely performed).
11. Patients with a known hypersensitivity or contraindication for iodinated contrast
media (iCM) which cannot be controlled by taking prophylactic measures (e.g.
temporary treatment interruption or introduction of adequate pre-medication).
12. Patients who cannot undergo PET/CT scanning (including but not limited to body size
and claustrophobia).
13. Any condition that in the opinion of the investigator may significantly interfere
with study compliance (including but not limited to psychological or psychiatric,
social or geographical condition potentially hampering compliance with the study
requirements).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
OLV Aalst
Address:
City:
Aalst
Zip:
9300
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
G. Huygh, Dr.
Facility:
Name:
AZ Delta CHIREC
Address:
City:
Brussels
Zip:
1070
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
C. Closset, Dr.
Contact backup:
Last name:
A. Awada, Dr.
Facility:
Name:
Cliniques Universitaires Saint-Luc
Address:
City:
Brussels
Zip:
1070
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
F. Duhoux, Prof.
Facility:
Name:
Free University Brussels (VUB)
Address:
City:
Brussels
Zip:
1070
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
C. Fontaine, Dr.
Facility:
Name:
Institut Jules Bordet
Address:
City:
Brussels
Zip:
1070
Country:
Belgium
Status:
Recruiting
Contact:
Last name:
E. De Azambuja, Prof.
Start date:
September 12, 2024
Completion date:
June 2025
Lead sponsor:
Agency:
ABSCINT NV/SA
Agency class:
Industry
Source:
ABSCINT NV/SA
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06369831
https://abscint.com/
