Alpha Tau Medical Ltd. has received FDA approval for its Investigational Device Exemption (IDE) application to conduct a multi-center study evaluating Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) for the treatment of recurrent cutaneous Squamous Cell Carcinoma (cSCC) in immunocompromised patients. The study, an investigator-initiated trial led by the Winship Cancer Institute of Emory University, will enroll up to 28 patients across eight U.S. institutions.
The trial will focus on patients with recurrent cSCC who have weakened immune systems due to primary or secondary immunodeficiencies, excluding those with diabetes. The primary efficacy endpoint is the objective response rate (ORR), with secondary endpoints including progression-free survival, overall survival, local control up to twelve months post-treatment, and safety as measured by adverse events.
Addressing an Unmet Need in Immunocompromised Patients
Immunocompromised patients, particularly organ transplant recipients, face a significantly elevated risk of developing cSCC. A 2015 study in the Journal of Clinical Medicine indicated that non-melanoma skin cancers are a major cause of morbidity in organ transplant recipients, with cSCC being the most prevalent, occurring at a 65 to 100-fold higher rate compared to the general population. Furthermore, a 2003 article in the New England Journal of Medicine suggested that over 50% of Caucasian transplant recipients will eventually develop cutaneous carcinomas.
Uzi Sofer, CEO of Alpha Tau, stated, "As we continue to progress in our ReSTART multi-center pivotal trial for recurrent cutaneous SCC, a number of investigators asked about the ability to treat immunocompromised patients, who are ineligible for the ReSTART trial. Given the continued requests we receive from clinicians to help them treat immunocompromised patients, we are confident that a successful clinical trial can help deliver an important new potential alternative for these patients."
Alpha DaRT Mechanism and Rationale
Alpha DaRT is designed to deliver highly potent and conformal alpha-irradiation directly to solid tumors. The treatment involves intratumoral delivery of radium-224 impregnated sources. As the radium decays, its short-lived daughters release and disperse, emitting high-energy alpha particles that aim to destroy the tumor cells while sparing surrounding healthy tissue due to the short diffusion distance of the alpha-emitting atoms.
Zachary Buchwald, MD, PhD, Principal Investigator of the trial and Assistant Professor of Radiation Oncology at Winship Cancer Institute of Emory University, commented, "We are thrilled to be able to initiate this trial and pioneer the use of the Alpha DaRT in immunocompromised patients. As we continue to see the promise of the Alpha DaRT through our participation in the ReSTART trial, it is obvious to us that we need to use this treatment elsewhere, particularly in populations at risk such as this."
Clinical Significance
This trial addresses a critical gap in treatment options for immunocompromised patients with recurrent cSCC, who often have limited alternatives. A 2019 study in JAMA Otolaryngology – Head & Neck Surgery found that immunosuppression is independently associated with a 2.32-times increased risk of disease-specific death in cSCC patients, highlighting the need for effective therapies in this population.
Dr. Robert B. Den, Alpha Tau Chief Medical Officer, added, "This trial targets a particularly vulnerable population for whom treatment options are limited, which affords the ability to provide even more potential value to these patients. We are looking forward to treating patients in this trial soon."
