ACTION-1: A randomised phase Ib/3 trial of RYZ101 compared with standard of care in somatostatin receptor positive, well-differentiated gastroenteropancreatic neuroendocrine tumors with progression following 177Lu somatostatin analogue therapy

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Introduction: Well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are characterized by high-density expression of somatostatin receptors (SSTRs). RYZ101 (225Ac-DOTATATE) is a highly potent alpha-emitting radiopharmaceutical therapy (RPT) being developed for SSTR+ solid tumors. ACTION-1 is a 2-part, global, randomized, controlled, open-label, Phase 1b/3 trial of RYZ101. Part 1 (Phase 1b), an uncontrolled dose de-escalation study, is complete with no dose-limiting toxicities.

Aim(s): In part 2 (Phase 3), RYZ101 10.2 MBq (275 µCi) is compared with standard of care (SoC) in pts with advanced SSTR+ GEP-NETs and disease progression following prior 177Lu-labeled somatostatin analogues (SSA).

Materials and methods: Eligibility criteria: grade 1–2, well-differentiated, inoperable, advanced, histologically-proven, SSTR+ GEP-NETs progressing (RECIST v1.1) following 2–4 cycles of 177Lu-SSA; ECOG PS 0–2; adequate hematologic and renal function. Pts unresponsive to prior 177Lu-SSA (disease control <6m after last dose of 177Lu-SSA) are excluded. In Phase 3, pts are randomized (1:1) to RYZ101 10.2 MBq (275 µCi) q8w x4 or investigator’s choice SoC (everolimus, sunitinib, or high-dose long-acting SSA); crossover to RYZ101 is permitted at time of centrally reviewed progression. Primary endpoint: progression-free survival (PFS) by blinded independent central review (BICR) using RECIST v1.1. Secondary endpoints: overall survival; objective response rate and best overall response (BICR and investigator assessment); duration of response; disease control rate; PFS (investigator assessment); safety.

Conference:

Presenting Author: Singh S

Authors: Singh S, Tesselaar M, Strosberg J, Jacene H, Halperin D,

Keywords: RYZ101, Gastroenteropancreatic neuroendocrine tumor, Somatostatin receptor, Radiopharmaceutical therapy,