Alpha DaRT Plus Pembrolizumab Hits 100% Response Rate in HNSCC

A prospective single-arm study (NCT05047094) combining intratumoral alpha-radiation therapy with pembrolizumab (Keytruda) produced systemic responses in all evaluable elderly patients with locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC), with overall survival (OS) and progression-free survival (PFS) outcomes that compared favorably with those historically reported for standard treatment with pembrolizumab monotherapy in this setting.¹

Results from the study, which were presented at the American Head and Neck Society 12th International Conference on Head and Neck Cancer, showed that among 9 evaluable patients whose tumors expressed PD-L1 (combined positive score [CPS] ≥1), Alpha DaRT plus pembrolizumab produced a systemic objective response rate (ORR) of 100%, comprising 4 complete responses and 5 partial responses, for a complete response rate of 44%.¹ By comparison, pembrolizumab monotherapy in the CPS of 1 or higher population of KEYNOTE-048 (NCT02358031) achieved an ORR of approximately 19%.¹

Median OS was 18.2 months and median PFS was 5.4 months. In KEYNOTE-048, pembrolizumab monotherapy in a comparable population produced a median OS of 12.3 months and a median PFS of approximately 3.2 months.¹ These are cross-trial comparisons between studies with different designs and patient populations and should be interpreted with caution.

The study met the pre-specified success criterion built into its Simon two-stage adaptive design, which required more than 6 patients to respond before enrollment could be concluded for success. With every evaluable patient responding, that threshold was met and recruitment was completed.¹

Safety

No Alpha DaRT-associated serious adverse events were observed across the treated cohort. Across all patients, only 2 Alpha DaRT-related adverse events were reported, both grade 1 in severity.¹ Two patients died prior to response evaluation and were excluded from the efficacy analysis: one died before Alpha DaRT treatment was administered, and the other died shortly after treatment from an unrelated cardiovascular event.¹

Study Design and Patient Population

The study is a single-center, prospective, open-label, single-arm trial conducted at Hadassah University Medical Center in Jerusalem, Israel, evaluating Alpha DaRT in combination with pembrolizumab in patients with recurrent unresectable or metastatic HNSCC and PD-L1 CPS of 1 or greater. A total of 11 patients were enrolled (4 female, 7 male), with a mean age of 72 years (range, 52-96).

Patients received a lead-in dose of pembrolizumab, followed by insertion of Alpha DaRT sources into a target lesion; the sources were removed approximately 14 days later, and patients continued on pembrolizumab per standard dosing.² Tumor response was assessed systemically across all lesions, both those directly treated with Alpha DaRT and untreated lesions, using RECIST v1.1, and safety was graded using CTCAE v5.0.1.

"Elderly patients with recurrent or metastatic head and neck squamous cell carcinoma are among the most difficult we treat. Since KEYNOTE-048, pembrolizumab has been our first-line standard of care, but as a single agent it produces a response in fewer than one in five patients, and many are too frail to add chemotherapy. That unmet need is what led us to design the first study to combine Alpha DaRT with checkpoint inhibition, adding a localized, immune-activating alpha-emitting radiotherapy to the systemic treatment these patients are already receiving,” Aron Popovtzer, MD, director of the Sharett Institute of Oncology at Hadassah University Medical Center and the study's lead principal investigator, stated in a news release.¹

“The results are genuinely encouraging, and they exceeded our expectations. Every evaluable patient responded, including several complete responses, with improvements in both overall and progression-free survival relative to historic data on pembrolizumab alone and a safety profile that let patients stay on their standard treatment…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," added Popovtzer.

References

1. 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. News release. Alpha Tau Medical Ltd. July 21, 2026. Accessed July 21, 2026. https://finance.yahoo.com/healthcare/articles/alpha-tau-reports-positive-data-123000492.html

2. Alpha DaRT in combination with pembrolizumab in head and neck squamous cell carcinoma. ClinicalTrials.gov. NCT05047094. Updated July 21, 2026. Accessed July 21, 2026. https://clinicaltrials.gov/study/NCT05047094