Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

NCT ID: NCT05477576

Last Updated: 2026-01-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

288 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-24

Study Completion Date

2028-07-31

Brief Summary

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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.

Detailed Description

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Conditions

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GEP-NET Gastroenteropancreatic Neuroendocrine Tumor Gastroenteropancreatic Neuroendocrine Tumor Disease Neuroendocrine Tumors Carcinoid Carcinoid Tumor Pancreatic NET

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

RYZ101

Intervention Type DRUG

RP3D as determined in Phase 1b

Phase 3 - RYZ101

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

Group Type ACTIVE_COMPARATOR

RYZ101

Intervention Type DRUG

RP3D as determined in Phase 1b

Phase 3 - Standard of Care

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

Group Type ACTIVE_COMPARATOR

Everolimus

Intervention Type DRUG

Everolimus

Sunitinib

Intervention Type DRUG

Sunitinib

Octreotide

Intervention Type DRUG

High-dose octreotide

Lanreotide

Intervention Type DRUG

Lanreotide

Phase 3 - RYZ101, PK/ECG Substudy adhoc subcohort

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

Group Type ACTIVE_COMPARATOR

RYZ101

Intervention Type DRUG

RP3D as determined in Phase 1b

Interventions

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RYZ101

RP3D as determined in Phase 1b

Intervention Type DRUG

Everolimus

Everolimus

Intervention Type DRUG

Sunitinib

Sunitinib

Intervention Type DRUG

Octreotide

High-dose octreotide

Intervention Type DRUG

Lanreotide

Lanreotide

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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RayzeBio, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ye Yuan, MD

Role: STUDY_DIRECTOR

RayzeBio Sr. Medical Director

Locations

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Research Facility

Phoenix, Arizona, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Duarte, California, United States

Site Status COMPLETED

Research Facility

Irvine, California, United States

Site Status RECRUITING

Research Facility

Los Angeles, California, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Palo Alto, California, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

San Francisco, California, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

New Haven, Connecticut, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Washington D.C., District of Columbia, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Jacksonville, Florida, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Miami, Florida, United States

Site Status RECRUITING

Research Facility

Tampa, Florida, United States

Site Status RECRUITING

Research Facility

Atlanta, Georgia, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Iowa City, Iowa, United States

Site Status RECRUITING

Research Facility

Lexington, Kentucky, United States

Site Status RECRUITING

Research Facility

Glen Burnie, Maryland, United States

Site Status RECRUITING

Research Facility

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Boston, Massachusetts, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Troy, Michigan, United States

Site Status COMPLETED

Research Facility

Rochester, Minnesota, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

St Louis, Missouri, United States

Site Status RECRUITING

Research Facility

Omaha, Nebraska, United States

Site Status RECRUITING

Research Facility

New York, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

New York, New York, United States

Site Status RECRUITING

Research Facility

Cleveland, Ohio, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Columbus, Ohio, United States

Site Status RECRUITING

Research Facility

Portland, Oregon, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Philadelphia, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Research Facility

Nashville, Tennessee, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Houston, Texas, United States

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Salt Lake City, Utah, United States

Site Status RECRUITING

Research Facility

Seattle, Washington, United States

Site Status RECRUITING

Research Facility

Brussels, , Belgium

Site Status RECRUITING

Research Facility

Leuven, , Belgium

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Roeselare, , Belgium

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Brasília, , Brazil

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Rio de Janeiro, , Brazil

Site Status COMPLETED

Research Facility

São Paulo, , Brazil

Site Status ACTIVE_NOT_RECRUITING

Research Facility

London, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Toronto, Ontario, Canada

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Montreal, Quebec, Canada

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Clichy, , France

Site Status RECRUITING

Research Facility

Lille, , France

Site Status RECRUITING

Research Facility

Montpellier, , France

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Nantes, , France

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Research Facility

Villejuif, , France

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Amsterdam, , Netherlands

Site Status RECRUITING

Research Facility

Maastricht, , Netherlands

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Utrecht, , Netherlands

Site Status RECRUITING

Research Facility

Seoul, , South Korea

Site Status ACTIVE_NOT_RECRUITING

Research Facility

Barcelona, , Spain

Site Status RECRUITING

Research Facility

Madrid, , Spain

Site Status RECRUITING

Research Facility

Zaragoza, , Spain

Site Status COMPLETED

Countries

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United States Belgium Brazil Canada France Netherlands South Korea Spain

Central Contacts

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RayzeBio Clinical Trials

Role: CONTACT

+1 619 657 0057

Facility Contacts

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References

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Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720.

Reference Type DERIVED
PMID: 38753757 (View on PubMed)

Other Identifiers

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RYZ101-301

Identifier Type: -

Identifier Source: org_study_id

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