Alpha Tau Medical Shares Early REGAIN Data: 2 Complete Responses in Glioblastoma Study

Key Points

• Alpha Tau Medical reported early REGAIN data showing strong initial activity for its Alpha DaRT therapy in recurrent glioblastoma, including two complete responses in the first three treated patients and a third patient with a 30% tumor reduction.
• Safety and feasibility looked encouraging in the pilot trial, with investigators saying implantation was feasible and there were no unanticipated high-grade CNS side effects; however, two patients did experience seizures that were managed with steroids and antiepileptics.
• The company is seeking FDA permission to expand the study to seven additional patients and potentially two more sites, while also preparing future work in brain metastases and other combinations if the glioblastoma results continue to trend positively.

Alpha Tau Medical NASDAQ: DRTS presented early clinical results from the first three patients treated in its REGAIN study of Alpha DaRT for recurrent glioblastoma, with company executives and clinical investigators describing initial tumor responses and safety observations from the pilot trial.

The event was led by Raphi Levy, Alpha Tau’s chief financial officer, who was joined by founder and Chief Executive Officer Uzi Sofer, Chief Medical Officer Dr. Robert Den and Dr. Joshua Palmer, professor of radiation oncology and vice chair of advanced imaging and experimental therapeutics at The Ohio State University Comprehensive Cancer Center.

Alpha DaRT Technology and Trial Design

Dr. Den described Alpha DaRT as a treatment that uses alpha-emitting radiation delivered through biocompatible metallic seeds inserted directly into a tumor. He said the approach is designed to take advantage of alpha particles’ high potency in causing DNA damage while limiting radiation exposure to surrounding tissue because alpha particles have a very short range.

According to Den, the Alpha DaRT seed is coated with Radium-224, which begins a radioactive decay process after insertion into the tumor. The decay chain releases alpha particles within the tumor until it reaches stable Lead-208. Den said the amount of lead produced is “2 orders below normal blood levels of lead,” which he said supports the potential for retreatment without concern for lead toxicity.

For the brain program, Den said Alpha Tau developed a radial applicator that works with a standard neurosurgical biopsy needle. The applicator is designed to deploy seeds in an umbrella-like configuration through a single needle insertion. He said preclinical work showed a “death zone” of tumor cell kill with sharp dose falloff and no observed damage to surrounding tissue in the models shown.

Dr. Palmer said the REGAIN study is enrolling patients with recurrent glioblastoma that has progressed after prior radiation. Key eligibility criteria include age 18 to 85, tumor size of 3 centimeters or less, more than six months since the first course of radiation, up to three recurrences and RANO-defined disease progression.

The primary endpoint is safety and feasibility of implantation. Feasibility is defined as appropriate placement in more than seven of 10 patients, while grade 3 or higher central nervous system adverse events are used as the safety signal. The trial planned to enroll three patients first, with one-month intervals for safety monitoring, before FDA review and enrollment of the remaining seven patients.

Early Patient Outcomes

Palmer said the first three patients were male, ages 56 to 71, and each had a WHO grade 4, IDH wild-type tumor. The first two patients had unmethylated tumors, while the third had a hypermethylated tumor. All had previously received standard therapy and experienced recurrent disease.

• Patient 1: A 56-year-old man with an unmethylated WHO grade 4 tumor had three prior recurrences before enrollment. Palmer said the three-month post-treatment scan showed no identifiable tumor in the treated region, no edema around the implant area and a complete response. He said the patient had no dose-limiting toxicities, no CNS adverse events and remained symptom-free without evidence of disease progression.

• Patient 2: A 71-year-old man with a WHO grade 4 tumor had two recurrences before enrollment. Palmer said scans at one month and three months showed no lesion in the treated area. The patient developed a grade 3 seizure with Todd’s paralysis 10 days after seed insertion, was treated with higher-dose steroids and returned to baseline after approximately five to six days.

• Patient 3: A 56-year-old man with a hypermethylated WHO grade 4 tumor had one prior recurrence. Palmer said the patient had a breakthrough seizure three days after the procedure in what was described on MRI as a pseudoprogression event. At one month, the lesion was still present but had decreased in size by 30%, which Palmer said qualifies as stable disease by RANO and was “clinically relevant.” The patient returned to neurologic baseline after steroids and antiepileptics.

Palmer said all three patients were appropriately treated and that implantation was feasible and safe. He said there were no unanticipated high-grade CNS side effects, and all patients had tumor responses, including two complete responses and one 30% reduction.

Safety Questions and Adverse Events

During the question-and-answer session, Palmer attributed the seizure events to radiation-related inflammation rather than the insertion procedure, citing the timing and MRI findings. He said all three patients left the hospital after the required monitoring period and had no immediate procedural complications.

Palmer said breakthrough seizures can occur after radiation when inflammation develops around a treated lesion. He characterized the events as anticipated potential toxicities that should not interfere with efficacy. He also said enhancement observed around the implanted seeds was not viewed as a major concern in the early follow-up period, describing it as a likely local reaction to intense radiation and potentially a sign of immune activity around the tumor.

Regulatory and Development Plans

Den said Alpha Tau has submitted a request to the FDA to enroll the additional seven patients in the pilot study and has also requested permission for two additional sites to join Palmer’s site. He noted that the program has FDA Breakthrough Device designation, which he said should allow agency responses within 30 days.

Den said that if the 10-patient pilot continues to show similar trends, the company could move quickly toward a pivotal trial in recurrent glioblastoma. He also said Alpha Tau is part of the FDA’s Total Product Lifecycle Advisory Program for the glioblastoma indication, which allows more frequent discussions with the agency.

Looking beyond recurrent glioblastoma, Den said Alpha Tau anticipates submitting to the FDA within about a month to study Alpha DaRT in brain metastases. He said the company may also explore combinations with immunotherapies and other systemic treatments.

Broader Pipeline Context

Levy placed the glioblastoma update in the context of Alpha Tau’s broader pipeline. He said the company recently completed recruitment in its U.S. pivotal ReSTART study in recurrent cutaneous squamous cell carcinoma and expects data around the end of the year. He also pointed to the U.S. IMPACT trial in pancreatic cancer, where the FDA recently expanded the study to include additional chemotherapy regimens and more patients, with recruitment expected to finish roughly in the next quarter.

For the REGAIN glioblastoma study, Den said feasibility is known immediately after implantation, while safety is assessed at one and three months. He said final results could be reported approximately three to four months after the last patient is enrolled, while patients will continue to be followed for survival.

About Alpha Tau Medical NASDAQ: DRTS

Alpha Tau Medical Ltd. is a medical technology company headquartered in Ness Ziona, Israel, focused on developing targeted alpha-radiation therapies for the treatment of solid tumors. The company's core innovation, known as Diffusing Alpha-emitters Radiation Therapy (DaRT), employs short-lived radioactive isotopes to deliver high-energy alpha particles directly within or adjacent to tumor tissues. By harnessing the potent cytotoxic effects of alpha radiation, Alpha Tau Medical aims to offer a novel approach to brachytherapy that can potentially overcome radioresistance and spare surrounding healthy tissue.

The company's lead product, Alpha DaRT, is currently being evaluated in clinical studies for a range of indications including recurrent or metastatic head and neck cancers, skin cancers, and other solid tumors.

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