Phase Ib portion of the ACTION-1 Phase Ib/3 trial of RYZ101 in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) progressing after 177Lu somatostatin analogue (SSA) therapy: Safety and efficacy findings

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Introduction: RYZ101 (225Ac-DOTATATE) is an alpha-emitting radiopharmaceutical in development for SSTR2+ solid tumors.

Aim(s): ACTION-1 (NCT05477576) is a 2-part, global, randomized, controlled, open-label, Phase 1b/3 trial of RYZ101 in advanced, well-differentiated SSTR+ GEP NETs progressing after 177Lu-SSA therapy.

Materials and methods: The Phase Ib portion of the trial had a dose de-escalation/Bayesian optimal interval design with boundaries based on a dose-limiting toxicity (DLT) rate of 25%. Patients (pts) received RYZ101 IV q8w x4 cycles. Planned dose levels (n=6/level): Level 0 (starting dose) 120kBq/kg; Level –1 90kBq/kg; Level –2 60kBq/kg. DLT was assessed for 56d after the first RYZ101 dose. Treatment-emergent adverse events (TEAEs) were graded by NCI-CTCAE v5.0. Tumor response was assessed locally by RECIST v1.1.

Conference:

Presenting Author: Strosberg J

Authors: Strosberg J, Ulaner G, Halperin D, Mehr S, Kotiah S,

Keywords: Gastroenteropancreatic neuroendocrine tumor, Somatostatin analogue therapy, Somatostatin receptor positive, RYZ101,