Trial to compare 225Ac-PSMA-617 vs 177Lu-PSMA-617 for oligorecurrent prostate cancer

Investigators at the University of California, Los Angeles (UCLA) Health Jonsson Comprehensive Cancer Center have launched the phase 2 ANDROMEDA trial (NCT07150715), comparing use of an alpha-emitting radionuclide with a beta-emitting radionuclide when used alongside stereotactic body radiotherapy (SBRT) for recurrent, oligometastatic prostate cancer.¹

Patients in the trial will be randomly assigned to receive 2 cycles of ¹⁷⁷Lu-PSMA-617 (lutetium Lu 177 vipivotide tetraxetan) plus SBRT or 1 cycle of ²²⁵Ac-PSMA-617 plus SBRT. The study will build on findings from the phase 2 LUNAR trial (NCT05496959), which demonstrated that the addition of ¹⁷⁷Lu-PNT2002 to SBRT significantly improved progression-free survival (PFS) in patients with oligorecurrent hormone-sensitive prostate cancer (17.6 months vs 7.4 months; HR, 0.37; 95% CI, 0.22 to 0.61; P < .0001).

“While we have previously shown that adding lutetium-177-based therapy to SBRT can prolong survival without progression in recurrent prostate cancer, we think actinium-225 may be even more effective at targeting microscopic disease,” said co-principal investigator Amar U. Kishan, MD, in a news release on the study.¹ “By comparing the 2 treatments head-to-head, we hope to determine which approach provides the most durable cancer control.”

In total, the ANDROMEDA study plans to enroll approximately 107 adult patients with oligorecurrent prostate cancer per the presence of 1 to 5 asymptomatic lesions on PSMA-PET.³ To be eligible for enrollment, patients need to have an ECOG performance status of 2 or higher and no indication for urgent or emergent radiation.

The primary end point for the trial is PFS. Secondary end points include the incidence of adverse events, androgen deprivation therapy free survival, overall survival, duration of response, and local control. Quality of life will also be measured using the xerostomia inventory.

“By combining whole-body targeted radiopharmaceutical therapy with precise local radiotherapy, we hope to eliminate both visible tumors and microscopic disease,” added co-principal investigator Jeremie Calais, MD, PhD, in the news release.¹ “The ultimate goal is to improve long-term cancer control while preserving quality of life.”

Patients will be followed in the trial for up to 5 years.

REFERENCES

1. UCLA Health launches novel clinical trial for recurrent prostate cancer. News release. University of California – Los Angeles Health Sciences. January 16, 2026. Accessed January 30, 2026. https://www.uclahealth.org/news/release/ucla-health-launches-novel-clinical-trial-recurrent-prostate

2. Kishan AU, Valle LF, Wilhalme H, et al. 177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study. J Clin Oncol. 2025;43(36):3812-3821. doi:10.1200/JCO-25-01553

3. Alpha-Emitting Radionuclide or Beta-Emitting Radionuclide With Metastasis-Directed Stereotactic Body Radiotherapy for the Treatment of Recurrent, Oligometastatic Prostate Adenocarcinoma (ANDROMEDA). ClinicalTrials.gov. Last updated December 17, 2025. Accessed January 30, 2026. https://clinicaltrials.gov/study/NCT07150715