1822P - PSMA-alpha targeted radionuclide therapy (TRT) with or without prior PSMA-beta TRT

Background

PSMA-TRT has included either beta-emitters (Lutetium-177) or alpha-emitters (Actinium-225). Responses have been observed in patients treated with 225Ac after 177Lu, supporting sequential administration. There are no known data-driven normal organ dose limits for radionuclide therapy, with putative limits extrapolated from EBRT. Here, we evaluate baseline demographics and prior exposures for association with outcome following treatment with 225Ac-J591.

Methods

Patients treated on prospective clinical trials of 225Ac-J591 were retrospectively analyzed with focus on efficacy and adverse events (AEs) with prior therapies (Table). Kaplan-Meier method was used for time to event endpoints (overall survival/OS, progression-free survival/PFS). Fisher’s exact test for analysis of associations between categorical variables.

Results

No significant difference in efficacy of 225Ac-J591 with/without prior 177Lu-PSMA: PSA50 (52 vs 58%), PFS (4.03 vs 5.07 mo), or OS (16.4 vs 17.3 mo); no efficacy differences based upon prior Ra223. Gr 4 myelosuppression may be more common in those with prior 177Lu, though numbers are small (n=1 for ANC and Hb; 14 vs 7.8% Gr 4 plts, p=0.4). No differences in frequency of nausea, xerostomia, or pain were seen with/without prior 177Lu, but Gr 2 fatigue was more common in those with prior 177Lu (48 vs 17%, p=0.023). No treatment-related renal failure observed with short-term follow up +/- prior 177Lu. Similar AE trends were seen for Gr 4 heme AE with prior Ra223 exposure, but no trend for non-heme AEs. Those with ≥2 lines chemo may be more likely to have Gr 4 heme AE. Within limits of small sample size, higher exposure of sequential 177Lu, Ra223, EBRT, and 225Ac-J591 associated with higher rate of Gr 4 plts (p=0.031).

Table: 1822P

Conclusions

Alpha-TRT with 225Ac-J591 retains efficacy following beta-TRT and Ra223. Risk of Gr 4 plts appears highest in those with prior 177Lu and Ra223 and EBRT, but high-grade events are rare. New examination of organ dose-limits with TRT is warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Weill Cornell Medical Center.

Funding

Weill Cornell Medicine, Department of Defense, NIH.

Disclosure

J. Nauseef: Financial Interests, Advisory Board: AIQ Solutions. A.M. Molina: Financial Interests, Advisory Board: Eisai, Exelixis, Janssen. C.N. Sternberg: Financial Interests, Personal, Advisory Board, AD board and speaker at ESMO: Pfizer; Financial Interests, Personal, Advisory Board: MSD, AstraZeneca, Astellas, Sanofi-Genzyme, Roche-Genentech, Foundation Medicine, Immunomedics, Janssen; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board, Was the head if the oversignt committee, of Phase III trial but last meeting over 1 year ago: Seattle Genetics; Financial Interests, Personal, Other, AD board: BMS; Financial Interests, Personal, Other, Speaker, owned by Prostate Cancer Foundation: Uro Today; Financial Interests, Personal, Other, Speaker, CME activities: Medscape. D.M. Nanus: Financial Interests, Advisory Board: AstraZeneca. N.H. Bander: Financial Interests, Personal, Leadership Role, Leadership and Equity: Convergent Therapeutics, Xenimmune Therapeutics; Financial Interests, Personal, Stocks or ownership: Telix Pharmaceuticals. S.T. Tagawa: Financial Interests, Personal, Advisory Board: Convergent Therapeutics, AIkido Pharma; Financial Interests, Personal, Other, Consultant: EMD Serono, Telix Pharma, Blue Earth Diagnostics, POINT Biopharma, Myovant, Bayer, 4D Pharma, Gilead, Pfizer, Janssen, Astellas, AbbVie, Novartis, Seagen, Clarity, Merck, Myovant, EMD Serono; Financial Interests, Personal, Stocks/Shares: AIkido Pharma; Financial Interests, Personal, Other, Patent co-inventor: Gilead; Financial Interests, Institutional, Local PI: Medivation, Astellas, Janssen, Amgen, BMS, AstraZeneca, Bayer, Merck, Clovis, Seagen; Financial Interests, Institutional, Steering Committee Member: Gilead, Novartis, POINT Biopharma, Clarity, Ambrx, Promontory. All other authors have declared no conflicts of interest.