FDA greenlights phase 1 trial of alpha radioligand therapy in mCRPC

The FDA has granted clearance to an investigational new drug (IND) application for the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy AB001, thus enabling the launch of a phase 1 trial of the agent in patients with metastatic castration-resistant prostate cancer (mCRPC), ARTBIO announced in a news release.¹

"AB001 is a novel PSMA-targeted and Pb212-based radioligand therapy designed to treat patients with metastatic prostate cancer, one that we believe has the potential to increase the radioligand dose rate to tumors without higher toxicity to normal tissues," said Margaret Yu, MD, chief medical officer of ARTBIO, in the news release.¹ "Following FDA review, our phase 1 study may now move ahead. This is welcome news for patients who are eagerly awaiting new targeted treatment options and for investigators who are ready to begin screening patients for this trial."

Patients will be enrolled in the study through clinical trial sites across the US. The company plans to enroll patients through international sites once they secure additional regulatory approvals.

According to ARTBIO, “Clinical trial supply will be enabled by ARTBIO's proprietary Pb212 generator technology, AlphaDirect, with precursor isotopes being sourced from the U.S. Department of Energy.”

"Despite the availability of many treatment options, metastatic prostate cancer is still not a curable disease, requiring additional innovative treatments," said Oliver Sartor, MD, director of the transformational prostate cancer research center at East Jefferson General Hospital Cancer Center, New Orleans, Louisiana, and ARTBIO scientific advisory board member, in the news release.¹ "I'm grateful for ARTBIO's dedication and passion in this area and am excited about the difference that AB001 could make for patients."

Previous data on AB001

The IND clearance for AB001 follows encouraging biodistribution results from a phase 0 first-in-human study (NCT05725070) of the agent conducted in Norway.

The study enrolled a total of 3 patients with mCRPC that progressed on standard of care therapies. Patients ranged from 73 to 89 years of age. Each patient received a microdose of 9.4 ± 0.3 MBq IV AB001.

Overall, there were no adverse reactions to AB001. As expected with a microdose, there were no efficacy signals by prostate-specific antigen or alkaline phosphatase level, the authors reported.

Post-therapy SPECT/CT showed AB001 uptake in the most PSMA-avid lesion, but no clear uptake in other lesions. According to the authors, “This may be attributed to the lower PSMA-expression of these metastases (due to tumor biology and limited tumor progression) demonstrated by PSMA PET, combined with injected AB001 microdose and imaging system limitations.”

The authors also reported that normal tissue visibility of AB001—uptake clearly distinguishable from adjacent tissue—was observed in the kidneys, urinary bladder with contents, and the liver. Blood pool uptake, or uptake in the heart and/or large vessels, was also demonstrated. There appeared to be low salivary gland uptake, with no visualization demonstrated.

"This IND clearance represents critical progress in translating the unique biology of Pb212 into patient care," said Michael J. Morris, MD, professor of medicine, prostate section head at Memorial Sloan Kettering Cancer Center and ARTBIO clinical advisory board member, in the news release.¹ "With the ability to target radiation at the cellular level, this program has the potential to establish a new standard of care in metastatic prostate cancer."

REFERENCES

1. ARTBIO announces FDA clearance of IND application for lead alpha radioligand therapy AB001. News release. ARTBIO, Inc. September 9, 2025. Accessed September 9, 2025. https://www.prnewswire.com/news-releases/artbio-announces-fda-clearance-of-ind-application-for-lead-alpha-radioligand-therapy-ab001-302549360.html

2. Berner K, Hernes E, Kvassheim M, et al. First-in-human study of AB001, a prostate-specific membrane antigen (PSMA) targeted 212Pb alpha radioligand, in patients with metastatic castration resistant prostate cancer (mCRPC): Phase 0 experience. Presented at: 16^th European Multidisciplinary Congress on Urologic Cancers. Lisbon, Portugal. November 7-10, 2024. https://artbio.com/pdf/first-in-human-study-of-AB001-PSMA-Phase-0-experience.pdf