Improved baseline staging with 68Ga-FAPI-46 PET in non-small cell lung cancer – a pilot study

This pilot study evaluates 68Ga-FAPI-46 PET imaging for baseline staging in patients with newly diagnosed non-small cell lung cancer. The primary objective is to determine essential input parameters for adequate sample size calculation for a subsequent diagnostic study comparing the diagnostic accuracy of standard 18F-FDG PET/CT and brain MRI versus 68Ga-FAPI-46 as a PET tracer in this patient population. This is clinically relevant for establishing the foundation for future comparative diagnostic accuracy studies that may improve staging precision in non-small cell lung cancer.

The secondary objectives include:

• Determining the correlation between 68Ga-FAPI-46 PET and brain MRI in patients with brain metastases

• Evaluating the clinical necessity to perform additional investigations (imaging or biopsy) based on 68Ga-FAPI-46 PET findings

• Evaluating whether 68Ga-FAPI-46 PET leads to disease upstaging compared to standard imaging with 18F-FDG PET/CT and brain MRI

The sponsor did not provide information regarding the total number of participants enrolled in this trial. The study population includes adult patients aged 18 years and older diagnosed with biopsy-proven **non-small cell lung cancer** (**NSCLC**). Both male and female subjects are eligible for participation. Participants are required to have an **ECOG performance status** score of 0 to 2, indicating they are ambulatory and capable of self-care. The trial population was selected based on the requirement for ¹⁸F-FDG **PET/CT** imaging as part of their diagnostic workup or having already undergone this imaging procedure. Key inclusion criteria specify that participants must be able to undergo ⁶⁸Ga-FAPI-46 PET with low-dose CT within three weeks following their ¹⁸F-FDG PET/CT scan and must be willing and able to undergo brain **MRI** if not already performed or scheduled as part of routine care. All participants must provide signed and dated written **informed consent**. The sponsor did not provide specific information regarding lifestyle considerations such as diet, physical activity, or habits for this study population.

This is a phase IV, pilot, diagnostic study investigating the use of 68Ga-FAPI-46 PET imaging in patients with newly diagnosed non-small cell lung cancer. The primary objective is to determine essential input parameters for an adequate sample size calculation for a subsequent diagnostic study that will compare the diagnostic accuracy of standard 18F-FDG PET and brain MRI versus 68Ga-FAPI-46 as a PET tracer. The study evaluates the number and location of metastatic lesions detected by 68Ga-FAPI-46 PET that are not identified by 18F-FDG PET in combination with brain MRI, and conversely, lesions detected by the current standard of care but not by 68Ga-FAPI-46 PET. Secondary endpoints include the assessment of brain metastases detection, the number of patients requiring additional investigations based on 68Ga-FAPI-positive, 18F-FDG-negative lesions, and the number of patients whose disease stage is upstaged based on 68Ga-FAPI-46 PET/CT findings compared to staging with 18F-FDG PET/CT and brain MRI.

The trial is designed as a comparative diagnostic study where participants will undergo imaging with both tracers. The test product is 68Ga-FAPI-46, administered as a solution for injection/infusion via intravenous bolus at a maximum daily dose of 3 MBq/kg with a maximum total dose of 495 MBq. The comparator is Steripet 250 MBq/ml, containing fludeoxyglucose (18F), administered as a solution for injection at a maximum dose of 450 MBq. Both products are administered as single doses during the treatment period.

Eligible participants include patients aged 18 years or older with biopsy-proven non-small cell lung cancer requiring 18F-FDG PET/CT for diagnostic workup or with 18F-FDG PET/CT already performed. Participants must have an ECOG performance score of 0 to 2 and must be able to undergo 68Ga-FAPI-46 PET with low-dose CT within three weeks after 18F-FDG PET/CT. Participants must be willing and able to undergo brain MRI if not already performed or scheduled in regular care. Provision of signed and dated written informed consent is required for enrollment.

The study involves a screening visit to assess eligibility criteria, followed by the administration of 68Ga-FAPI-46 and subsequent PET imaging with low-dose CT. If not already completed as part of standard care, participants will undergo brain MRI. The 68Ga-FAPI-46 PET imaging must be performed within three weeks of the 18F-FDG PET/CT scan. The total duration of participant involvement is determined by the completion of all required imaging procedures and assessments. Early termination from the study may occur if participants withdraw consent, experience adverse events that preclude continuation, or if the investigator determines that continued participation is not in the participant's best interest. The estimated recruitment start date is February 2026, with an estimated study completion date of February 2027.

The experimental investigational medicinal product **68Ga-FAPI-46** is administered as a **solution for injection/infusion** containing the active substance (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 product is administered via **intravenous bolus** route. The **dosage** is weight-based at 3 **megabecquerels per kilogram** (MBq/kg), with a maximum total dose of 495 megabecquerels (MBq) per administration. The treatment period consists of a single administration.

The **comparator** agent used in this study is **Steripet 250 MBq/ml**, a solution for injection containing **fludeoxyglucose (18F)** as the active substance. This is a marketed medicinal product manufactured by GE Healthcare B.V. with marketing authorization number RVG 33033 in the Netherlands. The pharmaceutical form is a solution for injection administered via the **injection** route. The maximum daily dose is 450 megabecquerels (MBq), which also represents the maximum total dose per administration. The treatment period consists of a single administration.

Efficacy will be assessed through the determination of essential input parameters for the calculation of an appropriate sample size for a future prospective diagnostic study. The primary endpoints include the number and location of metastatic lesions detected on 68Ga-FAPI-46 PET but not on 18F-FDG PET in combination with brain MRI, as well as the number and location of metastatic lesions detected on 18F-FDG PET in combination with brain MRI but not on 68Ga-FAPI-46 PET. Secondary endpoints encompass the number of patients with brain metastases on brain MRI and on 68Ga-FAPI-46 PET, the number of brain metastases in patients with brain metastases on brain MRI and on 68Ga-FAPI-46 PET, the number of patients with at least one 68Ga-FAPI-positive, 18F-FDG-negative lesion for which an additional investigation is clinically necessary, and the number of patients whose disease stage is upstaged based on 68Ga-FAPI-46 PET/CT findings compared to staging based on 18F-FDG PET/CT and brain MRI. The 68Ga-FAPI-46 PET with low dose CT will be performed within three weeks after 18F-FDG PET/CT, and brain MRI will be conducted if not already performed or scheduled in regular care.