FDA Grants Fast Track Designation to RAD101 for Imaging of Recurrent Brain Metastases

US FDA

• The FDA has granted fast track designation to Radiopharm Theranostics’ novel imaging agent, RAD101.
• This indication is for distinguishing between recurrent disease and treatment effects in brain metastases, including cases involving leptomeningeal disease.
• RAD101’s clinical utility is currently undergoing investigation in an open-label, multicenter, phase 2b trial (NCT06777433).

The FDA has granted RAD101, a novel imaging agent, fast track designation for distinguishing between recurrent disease and treatment effects in brain metastases, including cases involving leptomeningeal disease. This designation is aimed at expediting the development and review of RAD101, which targets fatty acid synthase (FASN).¹

Fast track status allows for increased FDA interaction and rolling submission of data for future new drug application filings. If applicable criteria are met, RAD101 may also be eligible for priority review, potentially shortening the time to approval.

“The FDA’s fast track designation for RAD101 highlights the seriousness of recurrent brain metastases as a condition and the unmet medical need for innovative products that can differentiate between tumor recurrence and radiation necrosis or pseudoprogression,” said Radiopharm Theranostics chief executive officer and managing director Riccardo Canevari in a press release.

RAD101 and The Role of FASN in Cancer Imaging

RAD101 is an ¹⁸F-labeled small molecule PET imaging agent designed to bind to FASN, a biomarker overexpressed in many solid tumors, including those metastasizing to the brain. This aims to enable visualization of viable tumor tissue.

FASN is a multifunctional enzyme involved in fatty acid synthesis and is significantly upregulated in multiple solid tumors. This biomarker’s expression is not limited to any specific cancer subtype, enhancing the utility of RAD101 across tumor origins.

Data from an earlier phase 2a trial conducted at Imperial College London demonstrated high uptake of RAD101 in both pretreated and treatment-naive brain metastases. The uptake was consistent across different tumor types, suggesting tumor-agnostic utility. Furthermore, early evidence suggested a potential role for PET-MRI with RAD101 as a noninvasive predictor of overall survival, though further validation in larger cohorts is necessary.

RAD101’s clinical utility is now being investigated in a phase 2b open-label, multicenter trial.

About the Phase 2b Study of RAD101

The phase 2b, single dose, single arm study is enrolling 30 patients with suspected recurrent brain metastases originating from various solid tumors.² Enrollment is open to patients aged 18 years and older with one of the following histopathologically confirmed advanced solid tumors with known history of brain metastases: lung, breast, colon, kidney, or melanoma.

Additional inclusion criteria require patients to have undergone stereotactic radiosurgery (SRS) for their brain metastases before study screening with preplanning images available for submission to the centralized imaging reader as reference, suspected but not confirmed recurrent brain metastases in at least 1 but not more than 5 lesions previously treated with SRS based on gadolinium-enhanced volumetric MRI, and an ECOG performance status of 0 to 2. Patients also must have a creatinine clearance ≥ 60 mL/min according to the Cockroft-Gault formula, a life expectancy of at least 4 months, and not be scheduled to undergo a confirmatory biopsy to characterize MRI findings until after the day 1 study procedures are complete.

The study will consist of a 4-week screening period, a 3-day imaging and safety follow-up period, and a data collection period of up to 6 months. On day 1, patients will receive a single intravenous bolus dose of RAD101 at a target dose of 370 MBq (10 mCi), with an allowable range of 10% above or below the target, administered over up to 30 seconds, followed by a saline flush. A whole-brain PET scan will be performed approximately 60 minutes after dosing, with a window of 10 minutes before or after. A high-resolution MRI will be performed either concurrently with the PET scan or separately later the same day.

Safety assessments, including physical exam, vital signs, ECG, and laboratory tests, will be completed before dosing. Vital signs and ECG will be repeated approximately 30 minutes after administration, with a 5-minute margin. Patients will also have follow-up MRI scans and/or a biopsy according to their standard of care.

The primary end point of the trial is concordance between RAD101-positive lesions and conventional MRI findings (gadolinium-enhanced), while secondary end points include the imaging agent’s accuracy, sensitivity, and specificity in distinguishing true recurrence from treatment-related changes.

“RAD101 represents a promising advancement in improving diagnostic precision for brain metastases, offering hope for more effective clinical decision-making in the over 300,000 patients diagnosed annually in the US. We are excited to advance our phase 2 clinical trial and anticipate sharing topline results in the second half of 2025,” added Canevari in the press release.¹

REFERENCES:

1. Radiopharm Theranostics granted U.S. food and drug administration fast track designation for RAD101 imaging in brain metastases. News release. Radiopharm Theranostics. June 11, 2025, Accessed June 11, 2025. https://tinyurl.com/y79v7s2t

2. Phase 2b imaging study of RAD101 in participants with suspected recurrent brain metastases (RAD101). ClinicalTrials.gov. Updated March 17, 2025. Accessed June 11, 2025. https://clinicaltrials.gov/study/NCT06777433