3388 - A Phase II Trial In Progress: Alpha-emitting radioNucliDe or Beta-Emitting RadiOnuclide Combined With MEtastasis-Directed Stereotactic Body Radiotherapy for Oligorecurrent Prostate Adenocarcinoma (ANDROMEDA)
Presenter(s)
K. Taparra1, C. Felix1, S. Parmisano1, H. Wilhalme2, R. Nabong3, L. Stephanie3, M. Rettig4, R. E. Reiter5, A. E. Singer6, J. B. Weidhaas1, J. Czernin3, M. Allen-Auerbach3, L. Valle1, M. L. Steinberg1, J. Calais3, and A. U. Kishan1; 1Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 2University of California, Los Angeles, Los Angeles, CA, 3Department of Nuclear Medicine and Theranostics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 4Department of Medical Oncology, University of California, Los Angeles, Los Angeles, CA, 5Department of Urology, University of California, Los Angeles, Los Angeles, CA, 6Division of Hematology-Oncology, University of California Los Angeles Medical Center, Los Angeles, CA
Purpose/Objective(s): TBD
Background: The recent LUNAR study (NCT05496959) found that adding beta-emitting 177Lutetium-PSMA-targeted radioligand therapy (177Lu-PSMA) to stereotactic body radiation therapy (SBRT) more than doubled median progression-free survival (PFS) compared to SBRT alone in oligorecurrent hormone-sensitive prostate cancer (orHSPC), hazard ratio (HR)=0.37. However, the relative efficacy compared to novel alpha-emitting 225Actinium-PSMA-targeting (225Ac-PSMA) is unknown. The hypothesis is that 225Ac-PSMA will improve 2-year PFS by treating more micrometastases, given its higher radiobiologic effectiveness and very short particle path length. We aim to compare the relative benefit of 2 cycles of 177Lu-PSMA versus 1 cycle of 225Ac-PSMA followed by SBRT metastasis-directed therapy (MDT). Materials/Methods: ANDROMEDA (NCT07150715) is a phase II, non-blinded, single-center randomized trial for individuals with orHSPC and 1-5 PSMA-avid metastases outside the prostate/prostate bed (N1 and/or M1). Eligibility criteria include testosterone >150 ng/dL, =18 years, and ECOG performance status =2. Exclusion criteria include de novo metastatic disease, castrate-resistance (testosterone <50 ng/mL with rising PSA), ADT/chemotherapy within 6 months of enrollment, and neuroendocrine histology. Participants are randomized 1:1 to 2 cycles 177Lu-PSMA (7.4 GBq/cycle, 6 weeks apart) or 1 cycle of 225Ac-PSMA (8 MBq, once), followed by SBRT to all lesions 1-2 weeks after radioligand therapy infusion. The primary endpoint of PFS is defined as the time from randomization to either 1) a new PSMA-avid lesion or 2) local progression on PSMA-PET (>30% SUV increase) or 3) progression on CT (>20% increase in the sum of the longest axial lesion diameters) with a PSA rise. For those alive without progression, PFS will be censored at the time of the last scan. All randomized subjects will be analyzed based on intent-to-treat. Secondary endpoints include 24-month disease burden by PSMA-PET, physician-scored toxicity, patient-reported quality of life, ADT-free survival, local control of SBRT lesions at 24 months after last radionuclide infusion, and time-to-progression (locoregional, distant, new metastasis). We hypothesize that the 24-month post-SBRT PSA-based recurrence rate of 177Lu-PSMA will be ~50%, which will be reduced with 225Ac-PSMA to ~30% (PFS HR~0.51). We anticipate an accrual time of 1.5 years and a median follow-up time of 24-months. A sample size of 96 patients (48 per arm) would provide 80% power to detect the expected difference in PFS at a 0.1 alpha level. Assuming a 10% drop-out/screen failure rate, the target trial accrual is 107 patients. Early stopping guidelines include monitoring site-specific grade 4-5 toxicity with a safety threshold of 20% from the time of the first enrolled patient, which would trigger halting the trial and safety consultation. ANDROMEDA is currently open for enrollment. Results: TBD Conclusion: TBD