FDA Receives Pre-Market Approval Module for Novel Recurrent CSCC Therapy

Developers at Alpha Tau Medical have submitted the first module of a pre-market approval (PMA) application to the FDA for the use of Alpha DaRT® as a treatment for those with recurrent cutaneous squamous cell carcinoma (CSCC), according to a press release from the developers.¹

Investigators designed Alpha DaRT to facilitate highly potent, conformal alpha-irradiation via sources impregnated with radium-224 administered intratumorally. Upon the radium’s decay, short-lived daughters release from the sources and project high-energy alpha particles that may destroy the tumor. The investigational agent may spare the healthy tissue surrounding a tumor due to the alpha-emitting atoms travelling a short distance.

“Alpha Tau continues its fast pace of activity, charging forward in our pursuit of potential marketing authorizations across a wide range of tumors, with an eye toward future commercialization,” Uzi Sofer, chief executive officer at Alpha Tau, stated in the press release.¹ “The decision by the FDA to allow us to submit our PMA in a modular form will hopefully allow for ongoing FDA review and feedback as each module is submitted, and we look forward to this dynamic and efficient authorization review process with the FDA.”

Developers submitted the module in parallel to the ongoing ReSTART trial (NCT05323253) assessing Alpha DaRT among patients with recurrent CSCC, which is expected to complete patient enrollment in the first quarter of 2026. According to the press release, the FDA previously granted breakthrough device designation to Alpha DaRT for use among patients with recurrent glioblastoma multiforme and recurrent SCC of the oral cavity.

In March 2023, developers announced the enrollment and treatment of the first 2 patients participating in the ReSTART trial.² These patients underwent treatment at the University Cancer Center in Houston, Texas.

“Alpha DaRT can be a real breakthrough in the treatment of recurrent CSCC. These patients have exhausted the effective treatment options available to them, and Alpha DaRT may give these patients additional hope for a successful outcome,” Mark D'Andrea, MD, a radiation oncologist at University Cancer Center in Houston, stated in the press release on the treatment of the first 2 patients in the ReSTART trial.² “In my experience as a radiation oncologist, treatment with the Alpha DaRT is a quick and straightforward procedure that can often be done in the office setting or procedure room in the clinic without the need for hospitalization or a shielded radiation suite. The procedure is often done using a local anesthetic, with the patient returning after 2 weeks for removal of the sources. The patient should then be able to return to a normal daily routine quickly.”

As part of the multi-center ReSTART trial, an estimated population of 86 patients will receive DaRT seeds based on preplanned radiotherapy parameters, with volumetric imaging reassessments taking place 2 to 3 weeks following seed placement.³ The trial’s primary end points include the objective response rate and duration of response. Secondary end points include progression-free survival, overall survival, time of local control, quality of life, adverse effects related to DaRT seeds, and user experience.

Patients 18 years and older with histologically confirmed recurrent CSCC who have progressed on at least 1 standard-of-care therapy who are not indicated for surgery and standard radiotherapy are eligible for enrollment on the trial. Other eligibility criteria include having measurable disease per RECIST v1.1 guidelines, a tumor size of no more than 7 cm, an ECOG performance status of 0 to 2, and a life expectancy of at least 12 months.

References

1. Alpha Tau submits first pre-market approval module to the FDA for Alpha DaRT® for the treatment of recurrent cutaneous squamous cell carcinoma (cSCC). News release. Alpha Tau Medical Ltd. January 5, 2026. Accessed January 6, 2026. https://tinyurl.com/52sbdmz4
2. Treatment of 1st two patients in its pivotal multicenter recurrent skin cancer (ReSTART) trial. News release. Alpha Tau Medical Ltd. March 8, 2023. Accessed January 6, 2025. https://tinyurl.com/yj6ws9ww
3. A clinical study to assess the efficacy and safety of Alpha DaRT224 for the treatment of patients with recurrent cutaneous squamous cell carcinoma. ClinicalTrials.gov. Updated December 2, 2025. Accessed January 6, 2026. https://tinyurl.com/54r3cd8e