Evaluation of 68Ga-FAPI-46 PET Imaging in Gastrointestinal Cancers: A Prospective Interventional Single-Arm Study

The primary objective of this clinical trial is to evaluate the **validity** of 68Ga-FAPI-46 PET (positron emission tomography) both inter- and intraindividually in patients with gastrointestinal cancers. This is clinically relevant as it aims to establish the diagnostic performance of 68Ga-FAPI-46 PET in accurately identifying and assessing various gastrointestinal malignancies, including hepatocellular carcinoma, cholangiocarcinoma, gastric cancers, pancreatic cancer, colorectal cancer, and oesophageal cancer. The ability to reliably detect and evaluate these cancers can significantly impact patient management and treatment outcomes.

Secondary objectives include:

• Assessing the accuracy of 68Ga-FAPI-46-PET in detecting gastrointestinal cancers.
• Evaluating the impact of 68Ga-FAPI-46-PET on treatment management.
• Validating the correlation between histopathological FAP expression and 68Ga-FAPI-46 uptake intensity.
• Assessing the safety of a single imaging dose of 68Ga-FAPI-46 administered as an intravenous bolus injection.

The clinical trial involves participants diagnosed with **gastrointestinal cancers**, including hepatocellular carcinoma, cholangiocarcinoma, gastric cancers, pancreatic cancer, colorectal cancer, and oesophageal cancer. The study population comprises both male and female subjects aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less, indicating a relatively stable general health status. The trial does not include vulnerable populations. Participants were selected based on the presence of at least one detectable tumor lesion with a diameter greater than 1 cm and the requirement for surgery or biopsy within a specified timeframe. Women of childbearing potential are included only after confirming a negative pregnancy test. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the validity of **68Ga-FAPI-46 PET** imaging in patients with gastrointestinal cancers, including hepatocellular carcinoma, cholangiocarcinoma, gastric cancers, pancreatic cancer, colorectal cancer, and oesophageal cancer. This is a prospective interventional single-arm trial. The study will assess the positive predictive value, sensitivity, and specificity of the imaging technique, with histopathology or biopsy serving as the reference standard. The trial is expected to commence recruitment on March 3, 2025, and conclude by June 30, 2026.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility criteria are confirmed. Key inclusion criteria include a proven or suspected diagnosis of gastrointestinal cancer, the presence of at least one detectable tumor lesion, and an ECOG performance status of 2 or less. Women of childbearing potential must have a negative pregnancy test prior to participation. The study will involve the administration of the investigational product, **68Ga-FAPI-46**, via injection, with a maximum daily dose of 200 MBq. The treatment period is limited to a single day.

Following the inclusion visit, participants will attend follow-up visits to monitor the imaging outcomes and any adverse events. The primary endpoint is the positive predictive value of the imaging technique, while secondary endpoints include sensitivity, specificity, detection rate compared to standard imaging, and the impact on therapy management. The end-of-study visit will conclude the participant's involvement, which is expected to last approximately one day, with additional follow-up as needed for safety monitoring.

Participants may be withdrawn from the study if they experience significant adverse events, fail to comply with study procedures, or withdraw consent. The trial aims to provide valuable insights into the diagnostic capabilities of **68Ga-FAPI-46 PET** imaging in gastrointestinal cancers, potentially influencing future clinical practices and patient management strategies.

The clinical trial involves the use of an **experimental medication** known as 68Ga-FAPI-46, which is a **solution for infusion**. The active substance in this medication is chemically synthesized and is 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 medication is administered via **injection**. The maximum daily and total dose is 200 MBq (megabecquerels), with a treatment period limited to one day. The medication is not formulated for pediatric use and is not classified as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The focus is solely on the administration of the experimental medication, 68Ga-FAPI-46, to evaluate its efficacy in imaging gastrointestinal cancers through positron emission tomography (PET). Participant compliance with the dosing schedule is monitored to ensure adherence to the protocol. The trial aims to assess the validity of 68Ga-FAPI-46 PET imaging both inter- and intra-individually in patients diagnosed with gastrointestinal cancers.

Efficacy in this clinical trial will be assessed through a series of primary and secondary endpoints focused on the use of **68Ga-FAPI-46 PET** for imaging gastrointestinal cancers. The primary endpoint is the positive predictive value (PPV) of **68Ga-FAPI-46 PET** on a per-region and per-patient basis for the detection of gastrointestinal cancers, confirmed by histopathology or biopsy, with a target PPV of at least 75%. Secondary endpoints include the sensitivity and specificity of **68Ga-FAPI-46 PET** on a per-patient and per-region basis, compared to previous standard imaging, for the detection of tumor lesions confirmed by combined histopathology, biopsy, follow-up imaging, or clinical follow-up reference standards. Additional secondary endpoints involve the detection rate of **68Ga-FAPI-46 PET** versus standard imaging, inter-reader reproducibility, impact on therapy management, changes in staging or prognostic groups, and the association between **68Ga-FAPI-46 PET** uptake intensity and histopathologic FAP expression. The incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including vital signs and changes in laboratory parameters, will also be monitored.