FDA, Radiopharm Align on Phase 3 Trial of RAD101 for Brain Metastases

Radiopharm Theranostics has reached alignment with the US FDA on the design of a single pivotal phase 3 trial evaluating RAD101, an investigational PET imaging agent for patients with indeterminate brain metastases following radiotherapy. The multicenter study is expected to enroll approximately 280 patients with brain metastases originating from various solid tumor types.¹

The company announced the regulatory milestone on November 4, 2026, following receipt of the final meeting minutes from its end-of-phase 2 meeting with the US FDA. The trial's co-primary end points will assess the sensitivity and specificity of RAD101 PET imaging against a defined reference standard.

Radiopharm expects to complete its selection of a contract research organization in the fourth quarter of 2026, with site activations and patient dosing anticipated to begin in the first half of 2027. The company is also preparing clinical supply of fluorine-18–labeled RAD101 through its partnership with Siemens Healthineers, which will manufacture and distribute doses for the planned US registrational study.¹

RAD101 Targets Fatty Acid Synthase in Brain Metastases

RAD101 is a fluorine-18–labeled small-molecule imaging agent designed to selectively bind to fatty acid synthase (FASN), a multienzyme protein involved in de novo fatty acid synthesis. FASN is overexpressed in brain metastases from solid tumors, and Radiopharm is developing the agent to support the detection of cancer cells in the central nervous system.

The imaging agent is intended to address a diagnostic challenge in patients who have received radiotherapy for brain metastases: distinguishing recurrent tumor from treatment-related necrosis. Contrast-enhanced MRI is the preferred imaging method for intracranial metastatic disease, but findings on follow-up scans may be inconclusive, complicating decisions about whether patients need additional treatment or continued surveillance.

More than 300,000 patients in the United States are diagnosed with brain metastases annually. Improvements in systemic cancer therapies have contributed to increased attention to intracranial disease, as patients may experience longer control of extracranial tumors while brain metastases remain a clinical concern.

The phase 2b trial of RAD101 demonstrated 93% concordance between MRI and PET imaging in patients with suspected recurrence of brain metastases. The study also showed selective tumor uptake of RAD101, including uptake in lesions with equivocal MRI findings. These results were reviewed by the FDA during the end-of-phase 2 meeting.

In a statement, Riccardo Canevari, CEO and managing director of Radiopharm Theranostics, emphasized the potential clinical importance of distinguishing active disease from treatment effects.

“Accurately distinguishing recurrent tumor from treatment-related necrosis is one of the most important challenges physicians face when managing patients with brain metastases,” Canevari said.

He added that the distinction can help clinicians determine whether patients require additional intervention or can continue with observation and surveillance.

FDA Fast Track Designation and Development Plans

RAD101 previously received FDA fast track designation for its development in distinguishing recurrent disease from treatment effects in brain metastases originating from different solid tumor types, including leptomeningeal disease. The designation is intended to facilitate development and expedite review of therapies addressing serious conditions with unmet medical needs.²

Radiopharm cited the planned enrollment of approximately 280 patients as a relatively small registrational study compared with historical phase 3 imaging programs. The company noted that some prostate cancer imaging agents required 2 phase 3 trials enrolling more than 700 patients combined.¹

The planned phase 3 trial will further evaluate RAD101's diagnostic performance. Its results will be important in determining whether the imaging agent can provide a reliable approach to assessing suspected recurrent brain metastases after radiotherapy.

REFERENCES

1. Radiopharm Theranostics announces alignment with US FDA on single pivotal phase 3 trial for RAD101 in diagnosis of brain metastases. News release. Radiopharm Theranostics. November 4, 2026. Accessed November 4, 2026. https://tinyurl.com/4enn4y3k

2. Radiopharm Theranostics granted US Food and Drug Administration fast track designation for RAD101 imaging in brain metastases. News release. Radiopharm Theranostics. June 11, 2025. Accessed November 4, 2026. https://tinyurl.com/y79v7s2t