Radiopharm Theranostics Reports Positive Results from RAD204 and RAD101 Trials

Radiopharm Theranostics (ASX: RAD) has achieved a durable partial response in an ongoing Phase 1 Trial of its RAD204 investigational PD-L1-targeted lutetium-177 nanobody radiotherapeutic in patients with advanced solid tumours post-immunotherapy.

The company previously received positive recommendations from an independent data and safety monitoring committee allowing it to proceed with enrolling new patients into the trial after completion of the first two cohorts to the current highest dose of 90 millicurie (mCi).

Initial data from the first two patients in the third cohort demonstrated favourable tolerability and tumour reduction in target lesions, with both patients remaining on treatment.

Radiopharm confirmed there have been no dose-limiting toxicities observed in any of the cohorts to date while kidney uptake in the third cohort has been limited and does not represent a potential obstacle for escalation to a higher dosage.

Confirmed RECIST Response

The first patient in the third cohort achieved a durable confirmed RECIST (response evaluation criteria in solid tumours) partial response through four treatment cycles, and has remained progression-free beyond seven months.

They experienced a 19% reduction in target lesions from baseline after the first dose and a 43% reduction after the second, which was maintained through to the third dose.

The fourth and final dose resulted in a 35% reduction and continued to meet RECIST criteria for a partial response.

The second patient demonstrated an early 7% reduction in target lesions following the first treatment cycle and is progression-free with continued follow up for additional efficacy and safety assessments.

Broad Therapeutic Potential

Managing director Riccardo Canevari said preliminary results from all three cohorts indicated the broad therapeutic potential of RAD204 in PD-L1-associated malignancies, showing it as generally well-tolerated at the highest dose level.

“We are excited to announce positive initial data from the first two patients treated with RAD204 in the third dosing cohort, which showed favourable tolerability and tumour reduction in target lesions,” he said.

“We remain laser-focused on advancing the Phase 1 trial and anticipate releasing additional data that will support the therapeutic potential of RAD204 to treat PD-L1 associated malignancies.”

“The totality of data across our multiple dose cohorts supports our confidence in this program and is expected to inform the recommended dose for our planned Phase 2 clinical trial.”

RAD101 Study Results

Radiopharm has also announced positive data from a Phase 2b trial of RAD101 in 30 participants with suspected recurrence of brain metastases after radiotherapy.

The analysis of imaging data for all assessed lesions showed 93% concordance between MRI (magnetic resonance imaging) and PET (positron emission tomography) scans of brain metastases and substantial and selective tumour uptake of RAD101.

Furthermore, a total of 14 patients with evaluable six-month follow-up or biopsy data showed a preliminary 86% sensitivity (the measure of a scan’s ability to correctly identify patients with disease), representing a strong positive trend.

“The entirety of this dataset captures the strength and potential of RAD101 to address a difficult diagnostic challenge in neuro-oncology,” Mr Canevari said.

“Achieving the primary endpoint provides strong validation of our approach which supports the advancement of RAD101 into a registrational Phase 3 program and we look forward to continuing our [regulatory] discussions as we work toward bringing a more precise diagnostic tool to patients and clinicians.”

Brain Metastases Diagnosis

RAD101 is a novel imaging small molecule targeting fatty acid synthase radio-labelled with Fluorine-18 for the diagnosis of brain metastases from solid tumours of different origins.

In the US, more than 300,000 patients each year are diagnosed with cerebral metastases and the incidence of intracranial metastatic disease (IMD) continues to increase.

This is partly due to improvements in systemic therapy resulting in better control of tumours outside of the central nervous system.

RAD101 has received US Food and Drug Administration fast track designation status to distinguish between recurrent disease and treatment effect of brain metastases originating from solid tumours of different origins including leptomeningeal disease (when cancer spreads to the cerebrospinal fluid and membranes surrounding the brain and spinal cord).