Alpha Tau Medical Ltd. (NASDAQ: DRTS, DRTSW) has received FDA approval for an Investigational Device Exemption (IDE) supplement to expand its pilot trial of Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) for pancreatic cancer. The approval, announced on February 3, 2025, allows for a broader patient group to be included in the study, marking a significant step forward in the development of this innovative alpha-radiation cancer therapy.
The IDE supplement enables Alpha Tau to include an additional cohort of patients with locally advanced pancreatic cancer, increasing the total number of participants from 12 to 30. Each cohort, including those with metastatic disease, will now consist of 15 patients, and the trial will be conducted at up to 10 clinical sites across the United States.
Alpha DaRT: A Novel Approach to Solid Tumor Treatment
Alpha DaRT is designed to deliver highly potent and conformal alpha-irradiation directly to solid tumors. This is achieved through the intratumoral delivery of radium-224 impregnated sources. As the radium decays, it releases short-lived daughters that emit high-energy alpha particles, aiming to destroy the tumor while sparing surrounding healthy tissue. The technology was initially developed by Prof. Itzhak Kelson and Prof. Yona Keisari from Tel Aviv University.
Promising Interim Data and Clinical Trial Expansion
The FDA's decision to approve the IDE supplement follows the release of positive interim data from multiple clinical trials evaluating Alpha DaRT. These trials include safety and feasibility studies in pancreatic cancer, a combination study with pembrolizumab in recurrent unresectable or metastatic head and neck squamous cell carcinoma (HNSCC), and other ongoing clinical investigations.
Interim data from three ongoing feasibility and safety trials in Canada and Israel, involving 41 pancreatic cancer patients, showed a 100% success rate in delivering Alpha DaRT sources. The trials also demonstrated a strong safety profile, with only three serious adverse events (SAEs) reported out of 151 total adverse events potentially related to the treatment. Two of the three SAEs required brief hospitalizations, with all patients recovering fully.
Survival Benefits Observed in Pancreatic Cancer Trials
Among the 33 patients with a measured objective response, pooled analysis revealed an 18% objective response rate (ORR) and a 91% disease control rate (DCR). Excluding the first two patients who received deliberately low dosages for safety assessment, the analysis showed a 19% ORR and a 97% DCR.
Kaplan-Meier statistics indicated a median overall survival (OS) of 18.6 months after diagnosis or initiation of previous chemotherapy, and 10.9 months after treatment with Alpha DaRT.
Ad-hoc analyses of key subpopulations in the pancreatic cancer trials suggested potential benefits of Alpha DaRT, especially in patients with poor prognoses. For instance, patients who could not receive chemotherapy (n=8) showed a median OS of 7.5 months after diagnosis, compared to historical data suggesting 3-3.5 months for untreated pancreatic cancer.
Combination Therapy Shows Promise in HNSCC
Interim data from a study combining Alpha DaRT with pembrolizumab in patients with recurrent unresectable or metastatic HNSCC showed a 75% systemic objective response rate and a 37.5% systemic complete response rate. This compares favorably to historical benchmarks of 19% and 5%, respectively, for pembrolizumab alone in a similar population in Merck’s KEYNOTE-048 trial.
Management Perspective
"Following the incredible data that we released last week, analyzing disease control and overall survival in pancreatic cancer patients treated with Alpha DaRT, we welcome the news of this IDE supplement as we continue to move forward, full steam ahead, in our efforts to explore a new treatment for patients with this deadly disease as quickly as possible," said Alpha Tau CEO Uzi Sofer.
Future Directions
Alpha Tau intends to discuss with the FDA a potential U.S. trial exploring the combination of Alpha DaRT and pembrolizumab in patients with head and neck cancer, building on the promising results observed in the ongoing HNSCC trial.
