First Immunocompromised Patient with cSCC Treated With Intratumoral Alpha DaRT

The first patient was treated successfully with Alpha DaRT (diffusing alpha-emitters radiation therapy) in a trial of immunocompromised patients with recurrent cutaneous squamous cell carcinoma (cSCC), according to a news release.¹

Because immunocompromised individuals represent a population at high risk of developing cSCC and are also often unable to receive immune checkpoint inhibitors as treatment, alternative options are crucial in this disease space. The ADMIRE study (NCT06615635) is designed for this population in particular.

“Our team has treated multiple patients under Alpha Tau’s ReSTART trial [NCT05323253] for recurrent cSCC, and that experience is exactly what gave us the confidence to bring Alpha DaRT to our immunocompromised patients through ADMIRE,” Michael Samuels, MD, chief of multidisciplinary programs at Banner MD Anderson Cancer Center in Gilbert, Arizona, who performed the procedure, stated in the news release.

Rationale for the Study

Immunosuppression, whether resulting from solid organ transplantation, hematologic malignancies such as chronic lymphocytic leukemia, or long-term treatment for autoimmune disease, is among the strongest known risk factors for cSCC, with an estimated 17 million adults in the United States live with immunosuppression, and organ transplant recipients specifically face a 65- to 100-fold higher incidence of cSCC than the general population.

The company noted that localized cSCC treatments become progressively more difficult in this population, as surgical excision carries a greater cumulative morbidity and surgical fatigue with repeated procedures and the reuse of radiation therapy is not advised because of cumulative dose limits. Immune checkpoint inhibitors that can be used to treat recurrent or advanced cSCC can lead to organ rejection in transplant recipients, and immunosuppressive therapy must be reduced once cancer is diagnosed, also raising rejection risk. For this reason, cSCC clinical trials have typically excluded patients who are immunocompromised, limiting this population's access to novel treatment options.

Study Design

ADMIRE is a prospective, multicenter, open-label, single-arm study evaluating intratumoral Alpha DaRT in immunocompromised patients with recurrent cSCC. Initially announced in September 2024 as an investigator-initiated trial, the study is now company-sponsored and is designed to enroll up to 28 patients across up to 8 sites in the United States. Eligible patients must have histologically confirmed recurrent cSCC with a single lesion up to 7 cm in diameter. They cannot have distant or nodal metastatic disease, T4 disease, extensive perineural invasion, previously untreated disease, or mucosal SCC.²

The patients must be immunocompromised because of any primary or secondary immunodeficiency, including solid organ transplantation, hematologic malignancy, or chronic immunosuppressive therapy for autoimmune disease; diabetes alone is not considered to qualify.

The primary end point is objective response rate (ORR) based on best overall response per RECIST v1.1 criteria; secondary end points include progression-free survival, overall survival, and local control, evaluated over 12 months.

Alpha DaRT is designed to deliver conformal alpha irradiation to solid tumors through intratumoral placement of radium-224–impregnated sources while sparing surrounding healthy tissue, according to the company. The DaRT “seeds” are inserted into the cSCC tumors and will be removed in 14 to 21 days.¹

According to Samuels, the first treated patient had “exactly that situation” where few treatment options were available with recurrence after prior localized care, and the procedure went smoothly. “I’m looking forward to seeing how this patient, and the others who will follow, respond over the coming months,” he stated in the news release.

Broader Research on Alpha DaRT for cSCC

ADMIRE builds on the ongoing single-arm, open-label ReSTART pivotal trial for recurrent cSCC, which completed enrollment in May of 2026, as well as an earlier skin cancer study in which two-thirds of enrolled patients already had recurrent disease.

In ReSTART, 88 patients have been enrolled across the United States, Canada, and Israel; they must have cSCC that failed to respond to first-line standard-of-care therapy and are not indicated for surgery or conventional treatment. The coprimary end points are ORR and duration of response at 6 months from initial observation of response. The FDA granted breakthrough device designation for recurrent cSCC for this trial.³

REFERENCES

1. Alpha Tau Successfully Treats First Immunocompromised Patient with Recurrent Cutaneous Squamous Cell Carcinoma in its ADMIRE Study at Banner MD Anderson Cancer Center. News release. Alpha Tau. July 15, 2026. Accessed July 21, 2026. https://tinyurl.com/ycxud4a5

2. Alpha Radiation Emitters Device (DaRT) for the Treatment of Cutaneous SCC for Immunocompromised Patients (DaRT). ClinicalTrials.gov. Updated July 15, 2026. Accessed July 21, 2026. https://clinicaltrials.gov/study/NCT06615635

3. Alpha Tau Completes Patient Enrollment in its U.S. Pivotal Skin Cancer Study, Advancing Towards Goal of FDA Approval of Alpha DaRT® to Treat Recurrent Cutaneous Squamous Cell Carcinoma. News release. Alpha Tau. May 8, 2026. Accessed July 21, 2026. https://tinyurl.com/4559s66d