Alpha DaRT Elicits Complete Responses in Malignant Skin and Soft Tissue Cancers

The diffusing alpha-emitter radiation therapy, Alpha DaRT, was found to elicit complete responses (CRs) per RECIST v1.1 criteria in 10 patients with malignant skin and soft tissue cancers who are enrolled to an ongoing single-institution pilot feasibility trial (NCT04377360).¹

The trial has met its primary feasibility end point, as all patients enrolled to the trial have successfully received the radiation treatment. At approximately 12 weeks, all 10 tumors responded to the approach without any treatment-related serious adverse effects (AEs) observed.

“Alpha Tau is incredibly focused on the US market, which we see as the paramount market for the Alpha DaRT,” Uzi Sofer, the chief executive officer of Alpha Tau Medical Ltd., stated in a press release. “We have been successful thus far in demonstrating promising results around the world, but it was critical for us to generate data such as this in the United States as well, and we are very excited by the efficacy and safety data observed.”

The product was designed to permit highly potent and conformal alpha-irradiation of solid tumors through the intratumoral delivery of radium-224 impregnated sources. When the radium decays, its short-lived daughters are discharged from the source and diffuse as they release high-energy alpha particles that serve to eliminate the tumor. Because the alpha-emitting atoms spread only a short distance, the radiation is believed to mainly just impact the cancer and to be able to spare healthy surrounding tissue.

Several preclinical studies have found the product to be safe and effective in many indications, including tumors that are known to be resistant to standard radiotherapy.²

The study was designed to identify the feasibility of performing the procedure needed to administer radiotherapy to the cancer.³ The trial enrolled patients with malignant tumor of the skin or superficial soft tissue, including but not limited to, basal cell carcinoma, squamous cell carcinoma, melanoma, cutaneous angiosarcoma or leiomyosarcoma, Merkel cell carcinoma, liposarcoma, rhabdomyosarcoma, Kaposi sarcoma, angiosarcoma of the soft tissue, and secondary malignant tumors of the skin and superficial soft tissue like metastases from breast cancer, lung cancer, melanoma, kidney cancer and others.

Patients with recurrent disease must have had at least 1 standard therapy fail, including prior radiotherapy or surgery. The trial also enrolled those with metastases who will not be rendered free of disease by tumor resection and those with tumors determined to be inappropriate for resection by a surgeon for select reasons.

Other eligibility criteria included being older than 18 years of age, having an ECOG performance status ranging from 0 to 3, a life expectancy of 12 weeks or longer, a platelet count of at least 50,000/mm³, an international normalized ratio of prothrombin time of 1.8 or less, and creatinine of 1.9 mg/dL or less.

If patients had a contraindication to radiotherapy for their disease, received radiotherapy to the malignant sin or soft tissue in the last 6 months and/or at doses greater than 60 Gy, received anticoagulation or antiplatelet treatment, or had a high probability of non-compliance, they were excluded.

The DaRT sources were inserted utilizing the preplanned radiotherapy parameters, with a specified number and size of sources. About 2 to 3 weeks following placement of the sources, the placement was reassessed via volumetric imaging and were subsequently removed. Investigators evaluated response to the radiation treatment periodically 3 months following the removal of the device.

The primary outcome measures of the trial were to establish the feasibility of DaRT delivery and to identify the frequency and severity of AEs. Key secondary outcome measures included rate of tumor response per RECIST criteria, radiation exposure safety, stability assessment of DaRT sources post placement, and quality of life assessments using the Skindex-16 and the Skin Cancer Index.

The data from the trial brings Alpha Tau Medical Ltd. closer to launching a multicenter pivotal trial for skin cancer in the United States, according to Sofer. This trial is being planned for launch in 2022.

“I am very impressed with the results of the feasibility trial of Alpha DaRT,” Stephen M. Hahn, MD, former commissioner of the FDA and due diligence advisor to Healthcare Capital Corp. in its announced business combination with Alpha Tau, added in the release. “Achieving a 100% CR rate for a new cancer therapy with no product-related serious AEs is remarkable. As a medical and radiation oncologist, I believe the opportunity is compelling for the Alpha DaRT to offer new hope to numerous patients with difficult-to-treat solid tumors throughout the body, and this news is more evidence supporting this view.”

References

1. Alpha Tau announces results of first US clinical trial of Alpha DaRT in malignant skin & soft tissue cancers, showing complete response in all ten treated tumors at approximately 12 weeks and no product-related serious adverse events. News release. Alpha Tau Medical Ltd.; January 10, 2022. Accessed January 11, 2022. https://prn.to/3ndgSEU
2. The Alpha DaRT technology. Alpha Tau Medical Ltd. website. Accessed January 11, 2022. https://bit.ly/3nhU4nw
3. Feasibility trial of diffusing alpha-emitter radiation therapy (DaRT) for malignant skin & superficial soft tissue tumors. ClinicalTrials.gov. Updated August 10, 2021. Accessed January 11, 2022. https://clinicaltrials.gov/ct2/show/NCT04377360