Interview with Dr. Harold Jacob on Alpha DaRT for Pancreatic Cancer

Dr. Harold Jacob

Director of Advanced Gastrointestinal Endoscopy

Hadassah University Medical Center

Alpha TAU Medical VP Marketing Gideon Matthews, PhD recently sat with Dr. Harold Jacob, Director of Gastrointestinal Endoscopy, Hadassah University Medical Center, to discuss currently ongoing clinical trials of the Alpha DaRT® for the treatment of pancreatic cancer at Hadassah.

You have many decades of experience as a physician and gastroenterologist. What drew you to join the Alpha DaRT trials for pancreatic cancer?

Dr. Jacob: I have seen many pancreatic cancer patients in my practice over the years, and there’s a tremendous unmet need for effective treatments. These trials felt like an an opportunity to be a part of addressing these unmet needs in a novel approach.  On a personal note, it was also an opportunity to contribute to the study of a promising technology coming out of Israel which could potentially extend and improve quality of life for pancreatic cancer patients all over the world.

From a patient perspective, what do you see as the main potential benefits of the treatment?

Dr. Jacob:The most obvious potential benefit is tumor destruction: reducing tumor burden or rendering a lesion less aggressive. But there are also indirect possible advantages. The double-stranded DNA breaks caused by the alpha particles released from the Alpha DaRT may help stimulate the immune system to generate a response against the primary tumor and even against metastases elsewhere in the body.

Moreover, disrupting the tumor's structure can potentially allow chemotherapy to penetrate more effectively. This approach hasn’t been shown to interfere with other standard treatments the patient may be receiving. Patients can still receive chemotherapy or other therapies, while undergoing Alpha DaRT implantation. Alpha DaRT is a complementary modality that fits well within existing treatment plans.

What concerns do patients typically raise regarding the Alpha DaRT treatment?

Dr. Jacob: Surprisingly few. It’s important to note that the patients who are eligible for these trials have pancreatic cancer which is considered inoperable, so they understand the seriousness of their condition and the limited options they have. Most are actively seeking trials or procedures that might improve their quality of life or longevity.

Of course, we explain the potential complications just like we would with any procedure. But in general, patients are quite willing to accept these risks in light of the potential benefits.

Do you envision these trials being relevant for pancreatic cancer patients who have already started treatment and for those who are newly diagnosed?

Dr. Jacob: Yes. Our ongoing trials have generally involved patients who would not or could receive chemotherapy or those patients who had already started treatment regimens. And now, with the new trial which is being run at several sites in the US and here at Hadassah which is specifically focused on newly diagnosed patients, the goal is to be able to also treat earlier-stage patients, and we hope for even better results in that population.

We’re seeing significant demand - more patients want to enroll than we can currently accommodate. That’s why it’s so important, in my opinion, for more centers around the world to begin offering this therapy as part of a clinical trial.

How do you explain the Alpha DaRT treatment to your patients?

Dr. Jacob: Patients are often already familiar with endoscopic ultrasound (EUS), having undergone it for biopsy. Conveniently, the Alpha DaRT treatment uses the same approach. The patients fast beforehand, undergo sedation, and we insert an endoscope - all things they’ve experienced before.

The only difference is that instead of performing a biopsy, we insert small metallic sources - the “DaRTs” - directly into the tumor. It requires multiple insertions, but it’s easy for patients to understand and tolerate.

Do patients ask what alpha radiation is?

Dr. Jacob: Some ask basic questions. We explain that it’s a type of internal radiation - alpha particles - and that the exposure to the rest of their body is minimal.

What they care most about is whether they’ll face restrictions due to radiation, and in this case, the answer is almost none. It has been shown to be a well-tolerated and targeted approach.

Based on your experience so far, are you satisfied with the results?

Dr. Jacob: Yes. The first set of results - from our trials (PANC-2 and ALL) and the Montreal trial (PANC-1) - includes 33 patients whose data could be analyzed.

It’s clear from this preliminary data that the procedure is both safe and feasible, which were the main endpoints. Early analyses also show disease stabilization over 90 days and possibly longer. While these trials weren’t designed to evaluate survival, we’re seeing signals that suggest improved overall survival.

Pain relief has also been reported in some patients - enough so that it’s now a formal endpoint in upcoming trials. So as I mentioned before, I am extremely patient-focused, so for this data to show potential quality of life improvement and potential extension of life is exciting.

Do you see Alpha DaRT becoming part of your future clinical practice?

Dr. Jacob:If Alpha DaRT successfully completes its clinical trials and receives FDA approval to market, I believe it will be adopted, in my opinion, into most endoscopic oncology practices where technically feasible.

There are some limitations - patients with portal or splenic vein thrombosis, or varices, may be more complex as this may interfere with placement of the Alpha DaRT. Even there, I foresee interventional strategies to make the procedure accessible. In my view, it has the potential to become a standard part of pancreatic cancer care.

*It should be noted that Dr. Harold Jacob is engaged as a consultant for Alpha Tau Medical Ltd.

Alpha DaRT is not currently approved for use outside of a clinical trial.