Study Of RYZ101 Compared With SOC In Pts W Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

Study Overview

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

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.

N/A

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

DRUG: RYZ101
DRUG: Everolimus
DRUG: Sunitinib
DRUG: Octreotide
DRUG: Lanreotide

RYZ101-301

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-07-20	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-06-24
First Submitted that Met QC Criteria 2022-07-25	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-06-27
First Posted (ACTUAL) 2022-07-28	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
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.	DRUG: RYZ101 RP3D as determined in Phase 1b
ACTIVE_COMPARATOR: Phase 3 - RYZ101 Actinium 225 radiolabeled somatostatin analog (SSA) for injection	DRUG: RYZ101 RP3D as determined in Phase 1b
ACTIVE_COMPARATOR: Phase 3 - Standard of Care Investigator's choice of standard of care between everolimus, sunitinib, octreotide, or lanreotide.	DRUG: Everolimus Everolimus DRUG: Sunitinib Sunitinib DRUG: Octreotide High-dose octreotide DRUG: Lanreotide Lanreotide

Participant Group/Arm

Intervention/Treatment

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.

DRUG: RYZ101

RP3D as determined in Phase 1b

ACTIVE_COMPARATOR: Phase 3 - RYZ101

Actinium 225 radiolabeled somatostatin analog (SSA) for injection

DRUG: RYZ101

RP3D as determined in Phase 1b

ACTIVE_COMPARATOR: Phase 3 - Standard of Care

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

DRUG: Everolimus

Everolimus

DRUG: Sunitinib

Sunitinib

DRUG: Octreotide

High-dose octreotide

DRUG: Lanreotide

Lanreotide

Primary Outcome Measures	Measure Description	Time Frame
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

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: RayzeBio Clinical Trials

Phone Number: +1 619 657 0057

Email: clinicaltrials@rayzebio.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-2
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. 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

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
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Denis Ferreira, MD, RayzeBio Sr. Medical Director

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

PatientS

Caregivers

Clinical Trial Record