Radiopharm Theranostics Ltd (ASX:RAD)’s recent collaborations with international partners have boosted the company’s hopes that its RAD201 therapy can successfully combat breast cancer.
The company has announced the successful completion of its Phase 1 study investigating the safety, dosimetry and efficacy of RAD201 in HER2-positive breast cancer subjects.
RAD201 is a novel single domain antibody engineered to bind to the imaging isotope Tc-99m, which targets the human epidermal growth factor receptor 2 (HER2), a protein often associated with breast cancer.
HER2 overexpression in breast cancer is often associated with aggressive disease and poor prognosis.
The trial was focused on the diagnostic potential of RAD201, with plans to progress to trials of a therapeutic isotope once its capacity as a tool of diagnosis is established.
Shanghai trial in 40 patients
The study, conducted at Shanghai General Hospital under the direction of the hospital’s Director of Nuclear Medicine, Dr Jinhua Zhao, imaged 40 histopathologically-proven breast cancer subjects.
The procedure involved injecting the subject with RAD201, allowing time for the single-domain antibody to localise at the site of the HER2 positive cancer and clear from non-target organs, then imaging the subject two hours post-injection using a Single Photon Emission Computed Tomography (SPECT) camera.
"Excellent" imaging results
The company is buoyed by the results. It said the procedure returned uniformly excellent, easy-to-interpret images that demonstrated outstanding target-to-background visibility.
There is growing confidence in the potential of RAD201 SPECT imaging to be a fast and non-invasive way of gaining insight into HER2 overexpression in breast cancer primary and metastatic lesions.
The researchers did not observe any concerning safety signals, with the only minor adverse event reported as unrelated to RAD201.
“The images obtained were outstanding, and can provide clinicians with much more holistic and useful information on HER2 expression in both primary and metastatic neoplasms in breast cancers than the conventional IHC method of assessing HER2 expression,” said the lead clinician on the study, Dr Zhao.
These preliminary results are very encouraging for planning further studies to explore the potential of this single-domain antibody in theranostics applications.”
Compassionate-use patients in Germany
The treatment is also being deployed for compassionate use in five patients at University Hospital Aachen in Germany.
"RAD201 SPECT/CT imaging non-invasively visualises in vivo heterogeneity of HER2 expression in tumours and has displayed a clear delineation of active tumour manifestations when compared to standard of care FDG PET/CT, confirming the theranostics potential of this tracer,” the head of Nuclear Medicine at the University, Dr Felix Mottaghy MD, said.
“In patients on anti-HER2 treatment, RAD201 imaging showed response to treatment more precisely than FDG PET/CT. Given its beneficial biodistribution, RAD201, labelled with therapeutic isotopes, has the potential to become a theranostic agent.”
What next?
Based on these encouraging results, RAD plans to accelerate the development of RAD201. Plans are underway to initiate a Phase 1 therapy study for RAD202 as a company-sponsored Investigational New Drug (IND) recognised by the US Food and Drug Administration (FDA) in the first half of 2022.
RAD202 will be consist of the same single domain antibody construct as RAD201, but will incorporate the therapeutic, beta particle-emitting isotope, Re-188, which has the potential to kill cancer cells.
RAD’s approach of demonstrating efficacy with imaging, followed by targeted internal radiotherapy, is consistent with the company’s vision for improving cancer therapy and the lives of patients living with oncological diseases.