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- W3007389375 abstract "114 Background: Prostate-specific membrane antigen (PSMA) can be targeted by antibodies (Ab) or small molecule ligands labeled with potent α emitters (e.g. 225 Ac). Unlike ligands, Ab biodistribution does not include non-tumor organs such as the salivary glands, kidneys and small bowel. We performed a phase I single ascending dose Ab study. Methods: Eligibility: progressive mCRPC following at least 1 potent AR pathway inhibitor (ARPI; e.g. abi/enza) and docetaxel (or unfit/refuse chemo) without limit of # prior therapies provided adequate organ function. Baseline 68 Ga-PSMA11 PET was performed but not used for eligibility. Single-subject cohorts received a single infusion of 225 Ac-J591 until grade (Gr) > 1 attributable toxicity or dose level 5, then transition to 3+3 design. Cohort 1 = 13.3 KBq/kg with planned escalation up to dose level 7 (93.3 KBq/kg). Dose-limiting toxicity (DLT) defined as attributable Gr 4 heme or Gr 3/4 non-heme toxicity. Results: 22 men were treated on 7 dose levels; median age 72.5 (range 58-89), PSA 146.5 (4.8-7168.4); 82% with >2 prior ARPI, 64% chemo, 45% sipuleucel-T, 23% radium-223, 55% prior 177 Lu-PSMA. By standard imaging 82% bone, 36% lymph node, 9% liver mets. At the time of data cutoff, 1 of 6 men in cohort 6 (80 KBq/kg) had DLT (Gr 4 anemia and platelets); he had 4 prior cycles of 177 Lu-PSMA. No other attributable Gr >2 non-hematologic or Gr >3 heme AE (including 0 of 6 at the highest dose level). Low Gr temporary AE’s include: 16 (73%) with fatigue, 11 (50%) pain, 11 (50%) nausea, 6 (27%) with xerostomia (5 of 6 with prior 177 Lu-PSMA), 3 (14%) AST elevation. With follow-up ongoing, 60% with any PSA decline, 35% with >50% PSA decline. Of 10 with detectable baseline and 12-week CTC counts (CellSearch), 8 declined (45-100% decline); 5 (50%) with CTC count conversion. While PSMA uptake was not a prerequisite for treatment, all had some PSMA uptake on 68 Ga-PSMA11 PET/CT; 64% with SUV max >5x liver SUV, 14% 2.5x – 5x liver, and 23% with SUV max 0-2.5x liver SUV. Conclusions: PSMA-targeted alpha-emitter 225 Ac utilizing intact Ab J591 is well tolerated with early evidence of clinical activity in a pre-treated population, including the majority with prior 177 Lu-PSMA. Clinical trial information: NCT03276572." @default.
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- W3007389375 date "2020-02-20" @default.
- W3007389375 modified "2023-10-18" @default.
- W3007389375 title "Dose-escalation results of a phase I study of 225Ac-J591 for progressive metastatic castration resistant prostate cancer (mCRPC)." @default.
- W3007389375 doi "https://doi.org/10.1200/jco.2020.38.6_suppl.114" @default.
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