Alpha DaRT® Plus Pembrolizumab Achieves 100% Response Rate in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Clinical Summary: 

• Design/Population: This prospective study evaluated Alpha DaRT® (Diffusing Alpha-emitters Radiation Therapy) plus pembrolizumab in elderly patients with recurrent unresectable or metastatic PD-L1–positive head and neck squamous cell carcinoma.
• Key Outcomes: Among 9 evaluable patients, the combination achieved a systemic objective response rate of 100%, including 4 complete responses and 5 partial responses. Median overall survival was 18.2 months, median progression-free survival was 5.4 months, and no Alpha DaRT-related serious adverse events were reported.
• Clinical Relevance: These early findings suggest that adding Alpha DaRT® to pembrolizumab may enhance antitumor activity without adding substantial treatment-related toxicity, supporting further evaluation in larger, controlled studies.

Results from a prospective study demonstrated that Alpha DaRT® (Diffusing Alpha-emitters Radiation Therapy) combined with pembrolizumab achieved a 100% systemic objective response rate (ORR) among evaluable patients with recurrent unresectable or metastatic head and neck squamous cell carcinoma, supporting further investigation of the combination in larger studies.

These findings were presented at the American Head and Neck Society International Conference on Head and Neck Cancer in Boston, Massachusetts.

In this open-label, single-arm study, investigators enrolled 11 patients with recurrent unresectable or metastatic head and neck squamous cell carcinoma and a PD-L1 combined positive score (CPS) ≥1 using a Simon 2-stage adaptive design. Patients received a lead-in dose of pembrolizumab followed by intratumoral Alpha DaRT® implantation into a target lesion. The Alpha DaRT®sources were removed approximately 14 days later, after which patients continued pembrolizumab according to standard dosing. The primary end point was ORR, assessed according to RECIST version 1.1. Key secondary end points included overall survival (OS), progression-free survival (PFS), and safety. 

At the time of analysis, 2 patients died before response evaluation, leaving 9 patients evaluable for efficacy. One patient died before receiving Alpha DaRT®, and the other died shortly after treatment because of an unrelated cardiovascular event.

Among the 9 evaluable patients, the systemic ORR was 100%, including 4 complete responses and 5 partial responses, corresponding to a complete response rate of 44%. The study met the prespecified efficacy criterion of its Simon 2-stage adaptive design, allowing enrollment to conclude after more than 6 patients achieved an objective response. Median OS was 18.2 months, and median PFS was 5.4 months. Four patients remained alive at the time of analysis.

Although the study was not designed for direct comparison, investigators reported that these efficacy outcomes compared favorably with historical results from the phase 3 KEYNOTE-048 trial, in which pembrolizumab monotherapy achieved an ORR of approximately 19%, a median OS of 12.3 months, and a median PFS of approximately 3.2 months among patients with PD-L1 CPS≥1. The investigators cautioned that cross-trial comparisons should be interpreted carefully because of differences in study design and patient populations.

No Alpha DaRT®-related serious adverse events were reported. Two Alpha DaRT®-related adverse events occurred during the study, both of which were grade 1 in severity.

“To my knowledge, no other combination study with pembrolizumab has shown results like these in this patient population, and it is a real achievement to see a therapy add this much value on top of a checkpoint inhibitor,” stated Aron Popovtzer, MD, Hadassah University Medical Center, Jerusalem. “These are early data, and larger controlled studies are needed to confirm the benefit, but they make a compelling case for continuing to investigate Alpha DaRT with immunotherapy, both in head and neck cancer and across other solid tumors.”

These findings build on previous clinical experience with Alpha DaRT® and support continued investigation of the therapy in combination with immune checkpoint inhibitors for patients with recurrent or metastatic head and neck squamous cell carcinoma. According to Alpha Tau, the company is continuing discussions with the US FDA regarding the potential development of a larger US-based study evaluating Alpha DaRT® plus pembrolizumab in this setting.

Source: 

Alpha Tau. Alpha Tau reports positive data demonstrating 100% objective response rate and 18.2-month median overall survival with Alpha DaRT® in combination with pembrolizumab in locally advanced or metastatic head and neck cancer, surpassing the study's pre-specified threshold for success. Accessed on July 21, 2026. https://alphatau.com/alpha-tau-reports-positive-data-demonstrating-100-objective-response-rate-and-18-2-month-median-overall-survival-with-alpha-dart-in-combination-with-pembrolizumab-in-locally-advanced-or-metastat/