Radiopharm gives RAD101 a clear FDA-backed route to Phase 3

FDA clears a single pivotal path for RAD101

Radiopharm Theranostics (ASX:RAD, Nasdaq:RADX) has secured a more defined regulatory route for RAD101, with the U.S. FDA aligning on a single multicentre Phase 3 imaging trial rather than requiring multiple registrational studies. The trial is expected to enrol approximately 280 patients with indeterminate brain metastases after radiotherapy.

The study will assess whether RAD101 can distinguish recurrent tumour from treatment-related effects, a diagnostic problem that can leave physicians uncertain about whether further intervention is needed. Its co-primary endpoints will be sensitivity and specificity against a defined reference standard, with the trial designed to demonstrate performance above prespecified thresholds.

The agreement follows the company’s End-of-Phase 2 meeting with the FDA, for which final minutes have now been received. It formalises the framework reported after the October FDA meeting, when Radiopharm said the regulator had provided a constructive basis for moving RAD101 towards Phase 3.

Phase 2b data underpin the registration strategy

FDA reviewers considered data from RAD101’s Phase 2b trial, which reported 93% concordance between MRI and PET imaging in patients with suspected recurrence. The company also said RAD101 showed substantial and selective uptake in tumours, including lesions that were equivocal on MRI.

RAD101 is an imaging small molecule designed to bind fatty acid synthase, or FASN, a protein involved in fatty acid production that Radiopharm says is overexpressed in brain metastases from solid tumours. The company’s stated aim is to improve detection of active cancer in the central nervous system, although the Phase 3 study will determine whether the earlier imaging signal translates into the required diagnostic performance.

Trial preparation points to 2027 dosing

Radiopharm expects to complete its contract research organisation selection in the fourth quarter of 2026, then activate trial sites and begin dosing patients in the first half of 2027. Siemens Healthineers is expected to manufacture and distribute clinical doses of 18F-labelled RAD101 for the U.S. study under a previously announced partnership.

That timetable gives the program a clearer operational sequence, but it remains a plan rather than a clinical milestone. CRO appointment, site activation, patient recruitment, endpoint performance and any later FDA review are still outstanding. The company’s RAD101 funding update also highlighted the financial demands of advancing the broader clinical pipeline, making execution and funding capacity relevant alongside the regulatory progress.

Fast Track status raises the stakes for the pivotal readout

RAD101 has FDA Fast Track Designation for distinguishing recurrent disease from treatment effects in brain metastases originating from different solid tumours, including leptomeningeal disease. Radiopharm estimates that more than 300,000 patients are diagnosed annually with brain metastases in the U.S., while noting that contrast-enhanced MRI remains the preferred imaging method despite limitations in follow-up surveillance.

The new FDA alignment is therefore significant because it removes one layer of uncertainty around trial design, not because it establishes that RAD101 works or will reach approval. The key test now shifts from regulatory architecture to whether a single, relatively focused Phase 3 study can produce sufficiently robust sensitivity and specificity results across patients with different underlying cancers.