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NCT05477576PHASE3Recruiting

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

RayzeBio, Inc.

Start Date

3/24/2022

Completion Date

12/1/2030

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

RYZ101

DRUG

Everolimus

DRUG

Sunitinib

DRUG

Octreotide

DRUG

Lanreotide

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Conditions

GEP-NETGastroenteropancreatic Neuroendocrine TumorGastroenteropancreatic Neuroendocrine Tumor DiseaseNeuroendocrine TumorsCarcinoidCarcinoid TumorPancreatic NET

Locations

Research Facility

Phoenix, Arizona 85054

United States

Research Facility

Duarte, California 91010

United States

Research Facility

Irvine, California 92663

United States

Research Facility

Los Angeles, California 90095

United States

Research Facility

Palo Alto, California 94305

United States

Research Facility

San Francisco, California 94143

United States

Research Facility

New Haven, Connecticut 06510

United States

Research Facility

Washington D.C., District of Columbia 20010

United States

Research Facility

Jacksonville, Florida 32224

United States

Research Facility

Miami, Florida 33165

United States

Research Facility

Tampa, Florida 33607

United States

Research Facility

Atlanta, Georgia 30322

United States

Research Facility

Iowa City, Iowa 52242

United States

Research Facility

Lexington, Kentucky 40536

United States

Research Facility

Glen Burnie, Maryland 21061

United States

Research Facility

Boston, Massachusetts 02118

United States

Research Facility

Boston, Massachusetts 02215

United States

Research Facility

Troy, Michigan 48098

United States

Research Facility

Rochester, Minnesota 55905

United States

Research Facility

St Louis, Missouri 63110

United States

Research Facility

Omaha, Nebraska 68130

United States

Research Facility

New York, New York 10029

United States

Research Facility

New York, New York 10065

United States

Research Facility

Cleveland, Ohio 44106

United States

Research Facility

Columbus, Ohio 43221

United States

Research Facility

Portland, Oregon 97239

United States

Research Facility

Philadelphia, Pennsylvania 19104

United States

Research Facility

Pittsburgh, Pennsylvania 15232

United States

Research Facility

Nashville, Tennessee 37232

United States

Research Facility

Houston, Texas 77030

United States

Research Facility

Salt Lake City, Utah 84112

United States

Research Facility

Seattle, Washington 98109

United States

Research Facility

Brussels,

Belgium

Research Facility

Leuven,

Belgium

Research Facility

Roeselare,

Belgium

Research Facility

Brasília,

Brazil

Research Facility

Rio de Janeiro,

Brazil

Research Facility

São Paulo,

Brazil

Research Facility

London, Ontario

Canada

Research Facility

Toronto, Ontario M4N 3M5

Canada

Research Facility

Montreal, Quebec

Canada

Research Facility

Clichy,

France

Research Facility

Lille,

France

Research Facility

Montpellier,

France

Research Facility

Nantes,

France

Research Facility

Vandœuvre-lès-Nancy,

France

Research Facility

Villejuif,

France

Research Facility

Amsterdam,

Netherlands

Research Facility

Maastricht,

Netherlands

Research Facility

Utrecht,

Netherlands

Research Facility

Seoul,

South Korea

Research Facility

Barcelona,

Spain

Research Facility

Madrid,

Spain

Research Facility

Zaragoza,

Spain