Radiopharm Theranostics has reached agreement with the US Food and Drug Administration on the design of a single pivotal Phase 3 trial for RAD101, its imaging agent for brain metastases. The company says the study will be much smaller than the registration programs once needed for comparable diagnostic agents.
The company said today it had received the final minutes of its end-of-Phase 2 meeting with the regulator. The FDA agreed to a multicentre trial of about 280 patients with indeterminate brain metastases from a range of solid tumour types after radiotherapy. The co-primary endpoints will be the sensitivity and specificity of RAD101 PET against a defined reference standard. The trial is designed to show performance above prespecified thresholds.
RAD101 is a small molecule that selectively binds to fatty acid synthase, an enzyme complex that drives fatty acid synthesis and is overexpressed in brain metastases from solid tumours. Radiopharm says targeting this activity may allow more accurate detection of cancer cells in the central nervous system.
The FDA reviewed data from the company's Phase 2b trial. That trial showed 93 per cent concordance between MRI and PET imaging of brain metastases in patients with suspected recurrence. The results showed substantial, selective uptake of RAD101 in tumours, and PET detected tracer uptake in lesions that were equivocal on MRI.
Chief executive and managing director Riccardo Canevari said telling recurrence apart from the effects of earlier treatment remained a central problem in clinical practice.
"Accurately distinguishing recurrent tumour from treatment-related necrosis is one of the most important challenges physicians face when managing patients with brain metastases. This determination has profound implications for patient care, helping clinicians decide whether a patient requires additional intervention and treatment or can be managed with continued observation and surveillance. Existing imaging modalities often leave uncertainty, creating difficult clinical decisions for both physicians and patients. RAD101 has shown the potential to resolve diagnostic uncertainty in lesions that are equivocal on MRI, potentially offering a clearer assessment of active disease," Mr Canevari said.
He said the agreed design significantly reduced the scale of evidence the company would need to generate.
"We are grateful to the FDA for its constructive review of our clinical data and for aligning with us on a single, multicenter pivotal study design. Importantly, the approximately 280-patient trial is substantially smaller than many historical registrational imaging studies (i.e. prostate cancer imaging agents required two Phase 3 trials and more than 700 patients combined.) We believe this reflects the significant unmet medical need faced by patients with brain metastases from solid tumors. We look forward to advancing RAD101 into this pivotal study as we work to provide physicians and patients with a more reliable tool to guide critical treatment decisions."
Radiopharm said it expects to finish selecting a contract research organisation in the fourth quarter of 2026. It then plans to activate sites and begin dosing patients in the first half of 2027. Siemens Healthineers will manufacture and distribute the fluorine-18-labelled RAD101 doses for the US registration trial.
RAD101 already has FDA Fast Track Designation for distinguishing recurrent disease from treatment effect in brain metastases from solid tumours of different origins, including leptomeningeal disease.
The company points to a large and growing patient population. More than 300,000 people are diagnosed with brain metastases each year in the United States alone. Incidence is rising partly because better systemic therapies now control tumours outside the central nervous system for longer. Contrast-enhanced MRI remains the preferred imaging method, but Radiopharm notes it has limitations, especially in the follow-up surveillance scans used to guide care.
Earlier results from an Imperial College London Phase 2a trial of RAD101 showed significant tumour uptake regardless of where the cancer started. This held in patients who had received stereotactic radiosurgery and in those who had not. That study also suggested combined PET and MRI imaging might offer a non-invasive prediction of overall survival, which the company said warrants larger studies.
Radiopharm has one Phase 2 and five Phase 1 trials under way across solid tumours, including lung cancer, breast cancer and brain metastases.