Comparative Evaluation of 68Ga-FAPI-46 and 18F-FDG as PET Tracers in Estrogen Receptor-Positive Breast Cancer: A Pilot Study

The primary objective of this pilot study is to evaluate the **accuracy** of **68Ga-FAPI-46** compared to **18F-FDG** as a PET tracer in patients with **ER-positive breast cancer**. This comparison is clinically relevant as it may offer insights into more effective imaging techniques for staging and monitoring hormone-positive breast cancer, potentially leading to improved patient management and outcomes.

Secondary objectives include investigating the differences between **68Ga-FAPI-46 PET/CT** and **68Ga-FAPI-46 PET/MRI**. This analysis aims to determine the most effective imaging modality, which could enhance diagnostic precision and influence treatment planning in clinical practice.

The clinical trial focuses on **hormone-positive breast cancer** and involves a study population exclusively composed of female participants. The age range of the participants falls within the categories of 18 to 64 years. The trial does not include male subjects or any vulnerable populations. Participants are required to have a histopathologically confirmed diagnosis of estrogen receptor-positive breast cancer, either locally advanced or recurrent, with specific criteria such as a primary tumor size greater than 5 cm or the presence of axillary lymph node metastases. The trial population was selected based on their willingness and ability to undergo study procedures, and all participants have provided written informed consent. The sponsor has not provided information regarding the total number of participants in the study. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the accuracy of **68Ga-FAPI-46** compared to **18F-FDG** as a PET tracer in patients with **hormone-positive breast cancer**. This is a Phase 4, randomized, double-blind, controlled study. The trial is expected to commence on April 1, 2024, and conclude by March 1, 2027. Participants will be involved in the study for a maximum treatment period of one day, with the primary endpoint being the comparison of lesion detection between the two tracers. Secondary endpoints include the comparison of lesion detection between **68Ga-FAPI-46 PET/CT** and **68Ga-FAPI-46 PET/MRI**.

The study will begin with an inclusion visit, where potential participants will undergo screening to confirm eligibility based on criteria such as having histopathologically proven ER+ breast cancer and being diagnosed with locally advanced or recurrent breast cancer. Participants must provide written informed consent and be willing to undergo study procedures. Following the inclusion visit, participants will receive the investigational product, **68Ga-FAPI-46**, administered as a solution for injection/infusion via intravenous bolus use. The maximum daily dose is 3 MBq/kg, with a total dose not exceeding 495 MBq.

Follow-up visits will be scheduled to monitor the participants' response to the tracer and to collect data on the number of lesions detected. The end-of-study visit will mark the completion of the participant's involvement, where final assessments will be conducted. Participants may be terminated early from the study if they experience adverse reactions, withdraw consent, or if the investigator deems it necessary for safety reasons. The trial aims to provide valuable insights into the efficacy of **68Ga-FAPI-46** as a PET tracer in detecting lesions in hormone-positive breast cancer, potentially influencing future diagnostic practices.

The clinical trial involves the use of **68Ga-FAPI-46**, an experimental medication formulated as a **solution for injection/infusion**. This investigational product is administered via **intravenous bolus use**. The active substance in 68Ga-FAPI-46 is chemically derived and identified as (S)-2,2',2''-(10-(2-(4-(3-((4-(2-(2-cyano-4,4-difluoropyrrolidin-1-yl)-2-oxoethylcarbamoyl)-quinolin-6-yl)(methyl)amino)-propyl)piperazin-1-yl)-2-oxoethyl)-68Ga-[1,4,7,10]-tetraazacyclododecane-1,4,7-triyl)triacetate. The dosing regimen for this trial specifies a maximum daily dose of 3 MBq/kg, with a total maximum dose not exceeding 495 MBq. The treatment period is limited to a single day.

In this study, **68Ga-FAPI-46** is being compared to **18F-FDG**, a standard-of-care PET tracer, to evaluate its accuracy in detecting ER-positive breast cancer. The trial does not involve the use of a placebo or any other comparator treatment beyond the standard **18F-FDG**. Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol, although specific compliance monitoring methods are not detailed in the provided data.

Efficacy in this clinical trial will be assessed by evaluating the performance of **68Ga-FAPI-46** as a PET tracer compared to 18F-FDG in patients with estrogen receptor-positive (ER+) breast cancer. The primary endpoint involves determining the number of lesions detected on 18F-FDG PET but not on **68Ga-FAPI-46** PET, and vice versa. This comparison aims to establish the accuracy of **68Ga-FAPI-46** in identifying cancerous lesions.

Secondary endpoints will focus on the number of lesions detected on **68Ga-FAPI-46** PET/CT but not on **68Ga-FAPI-46** PET/MRI, and vice versa. These assessments will provide insights into the efficacy of **68Ga-FAPI-46** across different imaging modalities. The trial is designed as a Phase 2 study, with the objective of refining the use of **68Ga-FAPI-46** in clinical settings for ER+ breast cancer. The study will involve a detailed analysis of imaging results to ensure comprehensive evaluation of the tracer's efficacy.