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

NCT05477576 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RYZ101-301
• Study Type: interventional
• Target: 338
• Locations: 8 countries
• Sites: 54

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; Neuroendocrine Tumors; Gastroenteropancreatic Neuroendocrine Tumor; Gastroenteropancreatic Neuroendocrine Tumor Disease; Carcinoid; Carcinoid Tumor; Pancreatic NET

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Phase 1b: RP3D

  Incidence of DLTs during the first 56 days of study treatment will be assessed.

  56 days of study treatment

• Phase 3: PFS as determined by BICR

  PFS will be defined as the time from the date of randomization until the date of progression (as determined by BICR from tumor assessments using RECIST v1.1) or death due to any cause, whichever occurs earlier.

  After the target number of 143 PFS events have occurred

Study Arms (4)

Phase 1b - RYZ101

EXPERIMENTAL

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.

Drug: RYZ101

Phase 3 - RYZ101

ACTIVE COMPARATOR

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

Drug: RYZ101

Phase 3 - Standard of Care

ACTIVE COMPARATOR

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

Drug: Everolimus; Drug: Sunitinib; Drug: Octreotide; Drug: Lanreotide

Phase 3 - RYZ101, PK/ECG Substudy adhoc subcohort

ACTIVE COMPARATOR

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

Drug: RYZ101

Interventions

RYZ101 DRUG

RP3D as determined in Phase 1b

Phase 1b - RYZ101; Phase 3 - RYZ101; Phase 3 - RYZ101, PK/ECG Substudy adhoc subcohort

Everolimus DRUG

Everolimus

Phase 3 - Standard of Care

Sunitinib DRUG

Sunitinib

Phase 3 - Standard of Care

Octreotide DRUG

High-dose octreotide

Phase 3 - Standard of Care

Lanreotide DRUG

Lanreotide

Phase 3 - Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• RayzeBio, Inc.: lead

Study Sites (54)

Research Facility

Phoenix, Arizona, 85054, United States

ACTIVE NOT RECRUITING

Research Facility

Duarte, California, 91010, United States

COMPLETED

Research Facility

Irvine, California, 92663, United States

RECRUITING

Research Facility

Los Angeles, California, 90095, United States

ACTIVE NOT RECRUITING

Research Facility

Palo Alto, California, 94305, United States

ACTIVE NOT RECRUITING

Research Facility

San Francisco, California, 94143, United States

ACTIVE NOT RECRUITING

Research Facility

New Haven, Connecticut, 06510, United States

ACTIVE NOT RECRUITING

Research Facility

Washington D.C., District of Columbia, 20010, United States

ACTIVE NOT RECRUITING

Research Facility

Jacksonville, Florida, 32224, United States

ACTIVE NOT RECRUITING

Research Facility

Miami, Florida, 33165, United States

RECRUITING

Research Facility

Tampa, Florida, 33607, United States

RECRUITING

Research Facility

Atlanta, Georgia, 30322, United States

ACTIVE NOT RECRUITING

Research Facility

Iowa City, Iowa, 52242, United States

RECRUITING

Research Facility

Lexington, Kentucky, 40536, United States

RECRUITING

Research Facility

Glen Burnie, Maryland, 21061, United States

RECRUITING

Research Facility

Boston, Massachusetts, 02118, United States

ACTIVE NOT RECRUITING

Research Facility

Boston, Massachusetts, 02215, United States

ACTIVE NOT RECRUITING

Research Facility

Troy, Michigan, 48098, United States

COMPLETED

Research Facility

Rochester, Minnesota, 55905, United States

ACTIVE NOT RECRUITING

Research Facility

St Louis, Missouri, 63110, United States

RECRUITING

Research Facility

Omaha, Nebraska, 68130, United States

RECRUITING

Research Facility

New York, New York, 10029, United States

ACTIVE NOT RECRUITING

Research Facility

New York, New York, 10065, United States

RECRUITING

Research Facility

Cleveland, Ohio, 44106, United States

ACTIVE NOT RECRUITING

Research Facility

Columbus, Ohio, 43221, United States

RECRUITING

Research Facility

Portland, Oregon, 97239, United States

ACTIVE NOT RECRUITING

Research Facility

Philadelphia, Pennsylvania, 19104, United States

ACTIVE NOT RECRUITING

Research Facility

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Research Facility

Nashville, Tennessee, 37232, United States

ACTIVE NOT RECRUITING

Research Facility

Houston, Texas, 77030, United States

ACTIVE NOT RECRUITING

Research Facility

Salt Lake City, Utah, 84112, United States

RECRUITING

Research Facility

Seattle, Washington, 98109, United States

RECRUITING

Research Facility

Brussels, Belgium

RECRUITING

Research Facility

Leuven, Belgium

ACTIVE NOT RECRUITING

Research Facility

Roeselare, Belgium

ACTIVE NOT RECRUITING

Research Facility

Brasília, Brazil

ACTIVE NOT RECRUITING

Research Facility

Rio de Janeiro, Brazil

COMPLETED

Research Facility

São Paulo, Brazil

ACTIVE NOT RECRUITING

Research Facility

London, Ontario, Canada

ACTIVE NOT RECRUITING

Research Facility

Toronto, Ontario, M4N 3M5, Canada

ACTIVE NOT RECRUITING

Research Facility

Montreal, Quebec, Canada

ACTIVE NOT RECRUITING

Research Facility

Clichy, France

RECRUITING

Research Facility

Lille, France

RECRUITING

Research Facility

Montpellier, France

ACTIVE NOT RECRUITING

Research Facility

Nantes, France

ACTIVE NOT RECRUITING

Research Facility

Vandœuvre-lès-Nancy, France

RECRUITING

Research Facility

Villejuif, France

ACTIVE NOT RECRUITING

Research Facility

Amsterdam, Netherlands

RECRUITING

Research Facility

Maastricht, Netherlands

ACTIVE NOT RECRUITING

Research Facility

Utrecht, Netherlands

RECRUITING

Research Facility

Seoul, South Korea

ACTIVE NOT RECRUITING

Research Facility

Barcelona, Spain

RECRUITING

Research Facility

Madrid, Spain

RECRUITING

Research Facility

Zaragoza, Spain

COMPLETED

Related Publications (1)

• 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.

  PMID: 38753757 DERIVED

MeSH Terms

Conditions

Gastro-enteropancreatic neuroendocrine tumor; Neuroendocrine Tumors; Carcinoid Tumor; Adenoma, Islet Cell

Interventions

Everolimus; Sunitinib; Octreotide; lanreotide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Adenoma; Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Ye Yuan, MD

  RayzeBio Sr. Medical Director

  STUDY DIRECTOR

Central Study Contacts

RayzeBio Clinical Trials

CONTACT

+1 619 657 0057; clinicaltrials@rayzebio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 28, 2022
• Study Start: March 24, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (32); BE (3); KR (1); BR (3); ES (3); FR (6); NL (3); CA (3)