Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy (ACTION-1)

October 1, 2026 updated by: RayzeBio, Inc.

Phase 1b/3 Global, Randomized, Controlled, Open-label Trial Comparing Treatment With RYZ101 to Standard of Care Therapy in Subjects With Inoperable, Advanced, SSTR+, Well-differentiated GEP-NETs That Have Progressed Following Prior 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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

343

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • Belgium
      • Brussels, Belgium
        • Research Facility
      • Leuven, Belgium
        • Research Facility
      • Roeselare, Belgium
        • Research Facility
  • Brazil
      • Brasília, Brazil
        • Research Facility
      • Rio de Janeiro, Brazil
        • Research Facility
      • São Paulo, Brazil
        • Research Facility
  • Canada
    • Ontario
      • London, Ontario, Canada
        • Research Facility
      • Toronto, Ontario, Canada, M4N 3M5
        • Research Facility
    • Quebec
      • Montreal, Quebec, Canada
        • Research Facility
  • France
      • 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
  • Netherlands
      • Amsterdam, Netherlands
        • Research Facility
      • Maastricht, Netherlands
        • Research Facility
      • Utrecht, Netherlands
        • Research Facility
  • South Korea
      • Seoul, South Korea
        • Research Facility
  • Spain
      • Barcelona, Spain
        • Research Facility
      • Madrid, Spain
        • Research Facility
      • Zaragoza, Spain
        • Research Facility
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Research Facility
    • California
      • Duarte, California, United States, 91010
        • Research Facility
      • Irvine, California, United States, 92663
        • Research Facility
      • Los Angeles, California, United States, 90095
        • Research Facility
      • Palo Alto, California, United States, 94305
        • Research Facility
      • San Francisco, California, United States, 94143
        • Research Facility
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Research Facility
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Research Facility
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Research Facility
      • Miami, Florida, United States, 33165
        • Research Facility
      • Tampa, Florida, United States, 33607
        • Research Facility
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Research Facility
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Research Facility
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Research Facility
    • Maryland
      • Glen Burnie, Maryland, United States, 21061
        • Research Facility
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Research Facility
      • Boston, Massachusetts, United States, 02118
        • Research Facility
    • Michigan
      • Troy, Michigan, United States, 48098
        • Research Facility
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Research Facility
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Research Facility
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Research Facility
    • New York
      • New York, New York, United States, 10029
        • Research Facility
      • New York, New York, United States, 10065
        • Research Facility
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Research Facility
      • Columbus, Ohio, United States, 43221
        • Research Facility
    • Oregon
      • Portland, Oregon, United States, 97239
        • Research Facility
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Facility
      • Pittsburgh, Pennsylvania, United States, 15232
        • Research Facility
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Research Facility
    • Texas
      • Houston, Texas, United States, 77030
        • Research Facility
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Research Facility
    • Washington
      • Seattle, Washington, United States, 98109
        • Research Facility

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

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

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

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
Active Comparator: Phase 3 - RYZ101, PK/ECG Substudy adhoc subcohort

Actinium 225 radiolabeled somatostatin analog (SSA) for injection
Drug: RYZ101

RP3D as determined in Phase 1b

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1b: RP3D
Time Frame: 56 days of study treatment

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
Time Frame: After the target number of 143 PFS events have occurred

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

Collaborators and Investigators

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

Sponsor

RayzeBio, Inc.

Investigators

  • Study Director: Ye Yuan, MD, RayzeBio Sr. Medical Director

Publications and helpful links

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

General Publications

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 Major Dates

Study Start (Actual)

March 24, 2022

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

July 20, 2022

First Submitted That Met QC Criteria

July 25, 2022

First Posted (Actual)

July 28, 2022

Study Record Updates

Last Update Posted (Actual)

October 5, 2026

Last Update Submitted That Met QC Criteria

October 1, 2026

Last Verified

October 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RYZ101-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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