New Radiopharmaceutical Shows Antitumor Activity in Patients with Advanced Prostate Cancer | Newsroom

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Researchers at Weill Cornell Medicine have led a Phase 1 study of a new drug that delivers powerful radiation therapy directly and specifically to cancer cells in patients with advanced prostate cancer. The clinical trial showed that the “radiopharmaceutical” was well tolerated and showed promising antitumor activity, according to a new study published Nov. 2 in the Journal of Clinical Oncology.

The radiopharmaceutical 225AC-J591 was administered in one injection and consists of two parts: an antibody that helps find the cancer cells is linked to a molecule that delivers a lethal dose of radiation. Specifically, an antibody called J591 that targets a protein found on the surface of most prostate cancer cells called prostate-specific membrane antigen (PSMA) is linked to the radioactive isotope actinium-225, which emits high-energy alpha particles to destroy cancer cells. . Dr. Neil Bander, professor emeritus of urology at Weill Cornell Medicine, developed J591 in 1996. This antibody targets prostate cancer cells anywhere in the body, avoiding healthy tissues and organs.

“Despite significant progress in improving prostate cancer survival, there is still no cure for metastatic prostate cancer,” said lead author and principal investigator of the study Dr. Scott Tagawa, professor of medicine and medicine in urology at Weill Cornell Medicine and medical director of the genitourinary oncology program at NewYork-Presbyterian/Weill Cornell Medical Center. “Our results from this first-in-human study of a PSMA-targeted alpha emitter are very exciting and a testament to more than two decades of translational research at Weill Cornell Medicine.”

Prostate cancer is the second most common cause of death from cancer in men in the United States. For those whose cancer has spread (metastasized) to other parts of the body and does not respond to therapies that lower testosterone, the five-year survival rate is 34 percent, according to the American Cancer Society.

Benefits of using a drug that emits alpha particles

Previously, scientists at Weill Cornell Medicine radiolabeled J591 with beta particle emitters, such as lutetium-177 (177Lu). In previous Phase 1 and 2 studies, 177Lu-J591 effectively targeted metastatic sites with acceptable toxicity and showed encouraging signs of response and improvements in overall survival.

Dr.’s laboratory Bander also examined J591, attached to another molecule called actinium, which emits alpha particles. “Actinium is approximately four thousand times more powerful and has a shorter delivery range than lutetium, providing more energy to kill cancer cells with less damage to surrounding healthy tissue,” said Dr. Tagawa.

With the need for more treatment options, Dr. Tagawa conducted the Phase 1 study of 225Ac-J591 at Weill Cornell Medicine and Tulane University School of Medicine between October 2017 and January 2021. A total of 32 patients with metastatic prostate cancer received a single injection of the radiopharmaceutical: 22 patients received one of seven increasing dose levels, and then 10 patients in the expansion group received the highest dose.

Dr. Scott Maker

Promising Phase 1 trial results

The researchers found that 225AC-J591 had good antitumor activity against advanced metastatic prostate cancer and was well tolerated. Prostate-specific antigen (PSA) – an indication of the severity of cancer – fell by at least half in 47 percent of patients. In addition, 13 of 22 (59 percent) patients experienced a decrease in the number of circulating tumors. These results are encouraging signs that the treatment worked to destroy prostate cancer cells.

Most of the serious side effects involved low blood cell counts, and all were temporary. Because the highest dose level of 225Ac-J591 that could be given without serious side effects was not reached and only one dose was administered in the Phase 1 study, a follow-on combined Phase 1/Phase 2 study is now underway. The new study will further assess its safety and efficacy with split or multiple infusions at higher cumulative doses.

“These strong results are due to the multidisciplinary collaboration between medical oncologists and our nuclear medicine group,” said Dr. Tagawa, co-leader of the Experimental Therapeutics Program at the Sandra and Edward Meyer Cancer Center and member of the Englander Institute of Precision. Medicine. “We look forward to further developing 225Ac-J591 in a combined Phase 1/Phase 2 follow-on study and future studies. If successful, 225Ac-J591 could offer new hope for patients with metastatic prostate cancer.”

Cornell University has licensed this technology exclusively to Convergent Therapeutics, Inc., a clinical-stage pharmaceutical company focused on developing next-generation radiopharmaceutical therapies for prostate cancer and other cancers. Convergent is one of several startups launched with foundational technology developed at Weill Cornell Medicine. The Office of Enterprise Innovation, which accelerates the translation of scientific discoveries into medical breakthroughs, played a critical role in licensing this technology to Convergent.

The study was supported by funding from philanthropic donors from Weill Cornell Medicine, a Prostate Cancer Foundation Challenge Award, and grants from the National Institutes of Health (Weill Cornell Medicine Prostate Cancer SPORE Developmental Research Project 1P50CA211024-01 and ULI RR024996) and the U.S. Department of Public health. Defense (W81XWH-17-PCRP-IA).

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with outside organizations to promote scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see the profiles before Dr. Scott Maker And Dr. Neil Bander.

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