Alpha DaRT plus pembrolizumab produced responses in all evaluable elderly patients with PD-L1–positive recurrent/metastatic head and neck cancer.
Alpha DaRT, an investigational intratumoral alpha-particle radiotherapy device, combined with pembrolizumab (Keytruda) produced an objective response rate (ORR) of 100% among evaluable elderly patients with PD-L1 combined positive score (CPS)–positive recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to results from a prospective clinical trial (NCT05047094).1
Among the 9 patients evaluable for response, treatment produced 4 complete responses and 5 partial responses, for a 100% ORR and a 44% complete response (CR) rate. The median overall survival (OS) was 18.2 months and the median progression-free survival (PFS) was 5.4 months.
“These results reinforce two priorities at the heart of our strategy: establishing Alpha DaRT in localized, unresectable disease, and building the combination evidence to compete in the metastatic setting alongside blockbuster checkpoint inhibitors,” Uzi Sofer, the chief executive officer of Alpha Tau, stated in a news release. “Our interim data had already shown us that response rates with Alpha DaRT plus pembrolizumab were exceptionally high; what we were waiting for was the survival follow-up to confirm those responses would translate into real, lasting benefit. Now that the data have matured, the picture is even stronger. Combination trials like this one are central to how we intend to grow the platform. Showing that Alpha DaRT can be added to a systemic backbone safely, and with results like these, is exactly the kind of evidence we hope will define its role across our pipeline. And we won’t stop here: We are exploring, in ongoing discussion with the FDA, the possibility of a similar but larger study in the US.”
The single-center, prospective, open-label, single-arm study enrolled patients with recurrent unresectable or metastatic HNSCC and a PD-L1 CPS of 1 or higher, using a Simon 2-stage adaptive design intended to include up to 48 patients.2
Patients received a lead-in dose of pembrolizumab before intratumoral insertion of Alpha DaRT radium-224–impregnated sources into a target lesion; the sources were removed approximately 14 days later, and patients continued pembrolizumab per standard dosing. Systemic tumor response, encompassing both Alpha DaRT–treated and untreated lesions, was assessed using RECIST 1.1, criteria and safety was graded per CTCAE 5.0 criteria.
The primary end point was confirmed best overall response rate per RECIST 1.1 criteria. Secondary end points incldued safety, PFS, OS, and duration of response.
Eleven patients (4 female, 7 male) with a mean age of 72 years (range, 52-96) were enrolled; 2 patients died before response evaluation, 1 before receiving Alpha DaRT and the other shortly afterward of an unrelated cardiovascular event, leaving 9 patients evaluable for response.1
Beyond the top-line response and survival data, 4 of the 9 evaluable patients remained alive at the time of this analysis. Investigators noted that both the response rate and survival outcomes compare favorably with historical data for pembrolizumab monotherapy in a similar population, while cautioning that comparisons across unrelated studies are limited by differences in study design, patient populations, and other factors.
The results build on prior Alpha DaRT monotherapy data in head and neck and skin cancer, including a first-in-human study in which Alpha DaRT produced a 100% ORR and a 78.6% CR rate among evaluable patients with squamous cell carcinoma lesions in a population skewed toward elderly, heavily pretreated, and radioresistant patients.
No Alpha DaRT–related serious adverse effects (AEs) were reported across the treated cohort. Only 2 Alpha DaRT-related AEs occurred, and both were grade 1 in severity.
“It’s worth reading these results against the bigger picture of where our global clinical trial pipeline is heading,” Robert Den, MD, Chief Medical Officer of Alpha Tau, added in the news release. “We have strong preclinical data suggesting that Alpha DaRT may prime a systemic anti-tumor immune response, and we have clinical experience, including multiple studies in head and neck and skin cancer, showing that Alpha DaRT monotherapy carries a favorable safety profile in this population. What this study suggests is that combining Alpha DaRT with pembrolizumab can translate that immune-priming effect into a clinical survival benefit for patients with recurrent or metastatic head and neck cancer. These results reinforce our plan to validate the clinical benefit of Alpha DaRT in this patient population in larger studies, and they add another key data point to a pipeline that now spans head and neck, skin, pancreatic, prostate, and brain cancers, among others.”
