Alpha Tau Reports 100% Response Rate with Alpha DaRT Plus Keytruda in Early Head and Neck Cancer Study

Alpha Tau Medical Ltd. has reported positive clinical data for its investigational alpha-radiation therapy Alpha DaRT® in combination with pembrolizumab (Keytruda®) in elderly patients with locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC). Presented at the American Head and Neck Society (AHNS) 12th International Conference on Head and Neck Cancer, the study showed a 100% objective response rate (ORR) among evaluable patients, exceeding historical outcomes reported for pembrolizumab alone in this treatment setting.

Alpha DaRT Combines Local Alpha Radiation with Immunotherapy

Alpha DaRT (Diffusing Alpha-emitters Radiation Therapy) is an investigational localized radiotherapy that delivers alpha particles directly into tumors through implanted radioactive sources. Beyond local tumor destruction, preclinical evidence suggests the therapy may stimulate systemic anti-tumor immune responses, providing a scientific rationale for combining it with immune checkpoint inhibitors such as pembrolizumab.

Head and neck squamous cell carcinoma remains a significant global health challenge, with approximately 890,000 new cases diagnosed annually worldwide. Although pembrolizumab has become a first-line standard of care for recurrent or metastatic PD-L1-positive HNSCC following the KEYNOTE-048 trial (NCT02358031), many elderly or frail patients cannot tolerate chemotherapy, highlighting the need for more effective treatment options with manageable toxicity.

Early Clinical Study Shows Encouraging Efficacy

The ongoing prospective, open-label, single-arm study (NCT05047094) enrolled patients with recurrent unresectable or metastatic HNSCC whose tumors expressed PD-L1 Combined Positive Score (CPS) ≥1. Participants received an initial dose of pembrolizumab, followed by Alpha DaRT implantation into a target lesion, with pembrolizumab continued according to standard dosing. Tumor responses were evaluated using RECIST v1.1, while adverse events were graded using CTCAE v5.0.

Eleven patients were enrolled in the study, with nine remaining evaluable for efficacy after two patients died before treatment response assessment, including one before receiving Alpha DaRT and another from an unrelated cardiovascular event shortly after treatment. Among the evaluable patients, the combination therapy achieved a 100% objective response rate, comprising four complete responses (44%) and five partial responses. The treatment also demonstrated encouraging survival outcomes, with a median overall survival of 18.2 months and a median progression-free survival of 5.4 months.

These outcomes compare favorably with historical pembrolizumab monotherapy data from the KEYNOTE-048 trial, which reported an ORR of approximately 19%, median overall survival of 12.3 months, and median progression-free survival of approximately 3.2 months in a similar patient population. Cross-trial comparisons, however, should be interpreted cautiously because of differences in study design and patient characteristics.

Favorable Safety Profile Observed

Investigators reported no Alpha DaRT-related serious adverse events. Only two Alpha DaRT-associated adverse events occurred during the study, both classified as Grade 1 (mild). The study also met the predefined success criterion under its Simon two-stage adaptive design, allowing recruitment to conclude after more than six patients achieved objective responses.

Leadership Highlights Potential Combination Strategy

Chief Executive Officer Uzi Sofer said the mature survival data strengthen Alpha Tau’s strategy of expanding Alpha DaRT beyond localized disease into combination regimens with checkpoint inhibitors. He noted that the company is discussing the possibility of conducting a larger U.S. clinical study with the FDA.

Lead investigator Prof. Aron Popovtzer of Hadassah University Medical Center described the findings as particularly encouraging for elderly patients who are often unable to receive chemotherapy. He emphasized that although larger controlled trials are required to confirm the benefit, the results support continued investigation of Alpha DaRT with immunotherapy in HNSCC and potentially other solid tumors.

Future Development

Alpha Tau plans to continue advancing its combination strategy while expanding its broader Alpha DaRT development program across multiple solid tumors, including head and neck, skin, pancreatic, prostate, and brain cancers. The company intends to validate these early findings in larger controlled clinical studies as it continues regulatory discussions regarding future U.S. development.

Reference

Alpha Tau Reports Positive Data Demonstrating 100%