Recruiting
Phase 3

RYZ101 vs. SOC

Sponsor:

RayzeBio, Inc.

Code:

NCT05477576

Conditions

GEP-NET

Gastroenteropancreatic Neuroendocrine Tumor

Gastroenteropancreatic Neuroendocrine Tumor Disease

Neuroendocrine Tumors

Carcinoid

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

RYZ101

Everolimus

Sunitinib

Octreotide

Lanreotide

Study Details

Brief summary:

This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of RYZ101 compared with investigator-selected standard of care (SoC) therapy in Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following treatment with Lutetium 177-labelled somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or 177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity \[HA\]-DOTATATE.

Conditions

GEP-NET

Gastroenteropancreatic Neuroendocrine Tumor

Gastroenteropancreatic Neuroendocrine Tumor Disease

Neuroendocrine Tumors

Carcinoid

Study ID

NCT05477576

Start date

Mar 24, 2022

Status verified date

Mar, 2026

Completion date

Dec, 2030

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion:

  • Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-2. Ki67% <20% is not required for the ad hoc subcohort of the PK/ECG substudy.
  • Progressive, SSTR-PET positive (i.e., Krenning score 3 or 4) GEP-NET (GI or pancreas) following 2-4 cycles of treatment with 177Lu-labeled SSA. Must have achieved disease control for at least 6 months following Lu-177 SSA (archival tissue is not required for the ad hoc subcohort of the PK/ECG substudy). No time limit is defined between 177Lu-SSA treatment and randomization. There must be at least 1 SSTR-PET imaging-positive measurable site of disease (according to RECIST v1.1) and no RECIST v1.1 measurable metastatic lesions that are SSTR imaging-negative.
  • Adequate renal function, as evidenced by estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]) (Levey et al. 2009)
  • Adequate hematologic function, defined by the following laboratory results:
  • Part 2: Hemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL); ANC ≥1000 cells/µL (≥1000 cells/mm3); platelets ≥75 x 109/L (75 x 103/mm3).
  • Total bilirubin ≤3 x upper limit normal (ULN)
  • Serum albumin ≥3.0 g/dL unless prothrombin time is within the normal range

Exclusion:

  • Prior radioembolization
  • Significant cardiovascular disease, such as New York Heart Association (NYHA) Class ≥II heart failure, left ventricular ejection fraction (LVEF) <40% or QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms for males and >470 ms for females.
  • Resistant hypertension, defined as uncontrolled blood pressure (BP) >140/90 mmHg while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic (Whelton et al. 2018)
  • Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HgB A1C) ≥8%
  • PRRT other than Lu-177 SSA (not applicable for ad hoc subcohort of the PK/ECG substudy)
  • Any condition requiring systemic treatment with high-dose glucocorticoids within 14 days prior to first dose of study treatment and/or which cannot be stopped while on study. Inhaled or topical steroids are permitted.
  • Prior history of liver cirrhosis or liver transplantation

Study Design

Enrollment

338 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1b - RYZ101

Part 1 is an uncontrolled dose de-escalation study to confirm the safety and determine the RP3D of RYZ101 based on Bayesian optimal interval design.

active comparator: Phase 3 - RYZ101

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

active comparator: Phase 3 - Standard of Care

Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.

active comparator: Phase 3 - RYZ101, PK/ECG Substudy adhoc subcohort

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

Interventions

RYZ101

RP3D as determined in Phase 1b

Everolimus

Everolimus

Sunitinib

Sunitinib

Octreotide

High-dose octreotide

Lanreotide

Lanreotide

Primary outcome measure

  • Phase 1b: RP3D [ Time Frame: 56 days of study treatment ]
  • Phase 3: PFS as determined by BICR [ Time Frame: After the target number of 143 PFS events have occurred ]

Central Contacts and Locations

Central contacts

RayzeBio Clinical Trials

+1 619 657 0057clinicaltrials@rayzebio.com

Locations

Research Facility

Recruiting

Irvine, California, United States, 92663

Research Facility

Recruiting

Miami, Florida, United States, 33165

Research Facility

Recruiting

Tampa, Florida, United States, 33607

Research Facility

Recruiting

Iowa City, Iowa, United States, 52242

Research Facility

Recruiting

Lexington, Kentucky, United States, 40536

Research Facility

Recruiting

Glen Burnie, Maryland, United States, 21061

Research Facility

Recruiting

St Louis, Missouri, United States, 63110

Research Facility

Recruiting

Omaha, Nebraska, United States, 68130

Research Facility

Recruiting

New York, New York, United States, 10065

Research Facility

Recruiting

Columbus, Ohio, United States, 43221

Research Facility

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Research Facility

Recruiting

Salt Lake City, Utah, United States, 84112

Research Facility

Recruiting

Seattle, Washington, United States, 98109

More Information

Sponsor

RayzeBio, Inc.

Last update posted

Mar 30, 2026

Last verified

Mar, 2026

Keywords

  • Neuroendocrine Tumors
  • SSTR+
  • GEP-NET
  • targeted radiotherapy
  • Gastroenteropancreatic Neuroendocrine Tumor
  • RayzeBio
  • Actinium
  • Ac 225
  • Dotatate
  • Everolimus
  • sunitinib
  • octreotide
  • lanreotide
  • PRRT
  • alpha emitter

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by RayzeBio, Inc. on 2026-03-30.