68Ga-FAPI-46 PET/CT for predicting histological response in triple-negative breast cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Curie

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Diagnosis [E01], Diseases [C] - Neoplasms [C04]

Trial duration

14 Oct 2024 → ongoing

Decision date (initial)

2024-04-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS/PHRCI 2022

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Diagnosis, Others

To determine whether the Total FAP-expressing tumor burden TFTB, biomarker extracted from initial 68Ga-FAPI-46 PET-CT imaging, could accurately predict the histological response to treatment of patients with early-stage high-risk TNBC undergoing neoadjuvant chemotherapy plus pembrolizumab.

Secondary objectives 6

1. To compare 68Ga-FAPI-46 PET/CT imaging (new tracer) with 18F-FDG PET/CT imaging (reference), in particular, on the detection of metastases and the assessment of total tumor burden.
2. To compare the predictive value (association with the histological response after neoadjuvant treatment) of biomarkers extracted from 68Ga-FAPI-46 PET/CT imaging, 18-FDG PET/CT imaging, and the combination of these two types of imaging
3. To compare the prognostic value (association with the risk of tumor recurrence and/or death from breast cancer after the entire therapeutic sequence: neoadjuvant, surgery, and adjuvant) of biomarkers extracted from 68Ga-FAPI-46 PET/CT imaging, 18F-FDG PET/CT imaging, and the combination of these two types of imaging
4. To develop a model from 68Ga-FAPI-46 PET/CT, 18F-FDG PET/CT imaging data to predict histological response after chemo-immunotherapy.
5. Exploratory: to compare functional imaging data of FAP+ CAFs and histological evaluation of CAF subpopulations, tumor-infiltrating lymphocytes (TILs) and tumor programmed death-ligand 1 (PD-L1) expression on biopsies.
6. Exploratory: to assess the impact of circulating tumor DNA (ctDNA) as a real-time method to monitor tumor burden and heterogeneity before and after neoadjuvant treatment (pre-surgery), along with their correlation with initial PET/CT scans (68Ga-FAPI-46 + 18F-FDG) and their relationship with clinical outcomes.

Conditions and MedDRA coding

Breast cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Female with age ≥ 18 years
2. Patients with previously untreated, non-metastatic, centrally confirmed TNBC for whom a neoadjuvant treatment with chemotherapy + pembrolizumab is the recommended option as standard of care,
3. Patients with measurable targets according to RECIST/PERCIST criteria
4. Patients without distant metastasis based on staging 18F-FDG PET/CT
5. Patients with tumor tissue available
6. Patients who provided a signed written informed consent,
7. Patient ability to comply with protocol requirements
8. Patients covered by a health insurance system

Exclusion criteria 6

1. Patients with prior anti-PD(L)1 immunotherapy
2. Pregnant and lactating women
3. Patients with any contra-indication to chemo-immunotherapy standard of care therapy, per investigator assessment
4. Patients with altered mental status or psychiatric disorder that, in the opinion of the investigator, would preclude a valid patient informed consent
5. Patients who have difficulty undergoing trial procedures for geographic, social or psychological reasons
6. Person deprived of liberty or under guardianship

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To measure the performance of 68Ga-FAPI-46 PET/CT imaging to predict complete histological response after neoadjuvant chemotherapy plus Pembrolizumab, in terms of Area under the ROC curve (AUC of the ROC curve)..

Secondary endpoints 6

1. Comparison of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT performances for: - detection of metastases (using the total number of metastatic lesion), - Evaluation of the tumor burden (using the total FAP expression tumor volume/TFTV* and the total metabolic tumor volume/TMTV*, respectively).
2. Comparison of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT predictive performances, separately and combined (association of biomarkers extracted from 68Ga-FAPI-46 PET/CT imaging, 18F-FDG PET/CT imaging with response to treatment).
3. Comparison of 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT prognostic performances, separately and combined (association of biomarkers extracted from 68Ga-FAPI-46 PET/CT imaging, 18F-FDG PET/CT imaging with recurrence and/or death from breast cancer).
4. Assessment of the predictive model performance combining 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT imaging data using sensitivity, specificity, positive and negative predictive values and area under curve the ROC curve(AUC of the ROC curve).
5. Exploratory: Correlation of 68Ga-FAPI-46 PET/CT imaging data with histological evaluation of CAF subpopulations (immunohistochemical staining for FAP), immune microenvironment (PD-L1 staining and TILs analysis) and comparison of the sensibility of 68Ga-FAPI-46 PET/CT imaging with that of histology.
6. Exploratory: Quantitative analyze of circulating tumor DNA (ctDNA) before and after neoadjuvant treatment (pre-surgery), and correlation of them with biomarkers extracted from initial PET/CT scans (68Ga-FAPI-46 + 18F-FDG) on the one hand, and histological response on the other.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Curie

Sponsor organisation

Institut Curie

Address

35 Rue Dailly

City

Saint-Cloud

Postcode

92210

Country

France

Scientific contact point

Organisation

Institut Curie

Contact name

Romain-David SEBAN

Public contact point

Organisation

Institut Curie

Contact name

Romain-David SEBAN

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications