Key Highlights

• Radiopharm Theranostics (NASDAQ:RADX) has reached alignment with the FDA on the design of a single pivotal Phase 3 trial for RAD101 in patients with brain metastases.

• The trial is expected to enroll approximately 280 patients, considerably smaller than some historical registrational imaging studies.

• RAD101 targets fatty acid synthase (FASN), which is overexpressed in brain metastases, and has received FDA Fast Track Designation.

• Siemens Healthineers will manufacture and distribute 18F-labeled RAD101 doses for the trial, with patient dosing expected in the first half of 2027.

Radiopharm Theranostics (ASX:RAD, NASDAQ:RADX), a clinical-stage biopharmaceutical company specializing in oncology radiopharmaceuticals, has announced a key regulatory milestone for its lead imaging candidate RAD101. The company has reached alignment with the U.S. Food and Drug Administration on the design of a single pivotal Phase 3 imaging trial following an End-of-Phase 2 meeting.

Trial Design and Scope

The pivotal, multicenter Phase 3 trial will evaluate RAD101 in patients with indeterminate brain metastases following radiotherapy. The study is designed to enroll approximately 280 patients with brain metastases from various solid tumor types who have undergone previous radiotherapy. The co-primary endpoints will be the sensitivity and specificity of RAD101 PET against a defined reference standard.

Notably, the trial size is substantially smaller than many historical registrational imaging studies. For comparison, prostate cancer imaging agents required two Phase 3 trials and more than 700 patients combined. Radiopharm CEO Riccardo Canevari attributed the streamlined design to the significant unmet medical need in the brain metastases population, with more than 300,000 patients diagnosed annually with brain metastases in the United States alone.

The Science Behind RAD101

RAD101 is a novel imaging small molecule that selectively binds to fatty acid synthase (FASN), an enzyme that is overexpressed in brain metastases from solid tumors. By targeting FASN activity, RAD101 aims to more accurately detect cancer cells in the central nervous system, potentially resolving diagnostic uncertainty that standard contrast-enhanced MRI cannot address. The company's Phase 2b trial demonstrated 93% concordance between MRI and PET imaging, with PET showing tracer uptake in lesions that were equivocal on MRI.

Distinguishing between recurrent tumor and treatment-related necrosis is one of the most significant diagnostic challenges in managing patients with brain metastases. Current imaging modalities often leave uncertainty, and the clinical determination has direct implications for whether patients require additional treatment or can be managed with observation.

Partnership and Next Steps

Radiopharm has partnered with Siemens Healthineers to manufacture and distribute clinical Supply of 18F-labeled RAD101 for the Phase 3 trial. The company expects to complete CRO selection in the fourth quarter of 2026, initiate site activations, and begin dosing patients in the first half of 2027. RAD101 has also received FDA Fast Track Designation for distinguishing between recurrent disease and treatment effects in brain metastases originating from solid tumors.

The Bottom Line

The FDA's alignment on a single, relatively compact Phase 3 trial represents a significant de-risking event for Radiopharm Theranostics. With clinical supply arrangements in place through Siemens Healthineers and a clear regulatory pathway, the company is positioning to advance RAD101 into pivotal development during the first half of 2027. The ongoing challenge of diagnosing brain metastases recurrence — affecting hundreds of thousands of patients annually — underscores the potential clinical relevance of this program.