Safety, tolerability and efficacy of 212Pb-DOTAMTATE as a targeted alpha therapy for subjects with unresectable or metastatic somatostatin receptor-expressing gastroenteropancreatic neuroendocrine tumors (SSTR+ GEP-NETs): A phase 2 study.

• DOI: 10.1200/jco.2024.42.16_suppl.4020
• Publication Date: 2024-06-17T14:16:54Z
• Authors: Jonathan R. Stros...; Shagufta Naqvi; Allen Lee Cohn; Ebrahim S Delpassand; Volker Jean Wagner; Izabela Tworowska; Julien Torgue; Rachel Woloski; Allison Manuel; Mary Alice Maluccio
• Keywords: Tolerability

4020 Background: 212 Pb-DOTAMTATE is a Targeted Alpha Therapy (TAT) in clinical development for subjects with SSTR+ neuroendocrine tumors. A phase I dose-escalation study has already been completed (Delpassand et al. J Nucl Med 2022). TAT holds the promise to improve outcomes versus Peptide Receptor Radionuclide (PRRT) beta-emitters like 177 Lu-DOTATATE, currently considered standard of care GEP-NETs. Methods: ALPHAMEDIX 02 Phase II, open-label, multicenter evaluating safety, tolerability and efficacy PRRT-naïve (Cohort 1, N = 36) PRRT-refractory 2, Target 30) histologically confirmed unresectable or metastatic GEP-NETs, positive somatostatin analogue imaging at least 1 site measurable disease per RECIST 1.1. was administered 67.6 μCi/kg cycle, maximum activity cycle 5.5 mCi every 8 weeks, up 4 cycles. Primary endpoints include overall response rate (ORR) RECIST1.1, incidence severity adverse events (AEs). Secondary progression free survival, survival , health-related quality life. Initial results cohort are presented. Results: In 17 out 36 GEP-NETs achieved (ORR 47.2% (32.0-63.0%)). trial, five eight PRRT- naïve treated same regimen 62.5% (30.6-86.3%)): combined ORR from both studies 50% (22 44, 95%-CI:36% - 64%). Median Duration Response (DOR) not reached studies. Four (80%) had DOR ≥ 12 months. ongoing II follow-up 10 shorter than 6 months: so far 7 (41%) months, one these Lymphocytopenia lead cause 59% grade 3 AEs reported 1. Overall, fatal were reported: death / progressive (N 2), carcinoid syndrome 1) sepsis 1). Conclusions: treatment cycles ²¹²Pb-DOTAMTATE (67.6 μCi/kg/cycle) well-tolerated, safety profile consistent underlying expected toxicities radioligand therapy, similar Lu-DOTATATE. The (50% pooled dataset) appears be substantially higher previously Lu-DOTATATE pivotal NETTER-1 18% (10–25%)). Clinical trial information: NCT05153772 .