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

March 27, 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

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
338

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Belgium
      • Brussels, Belgium
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Leuven, Belgium
        • Active, not recruiting
        • Research Facility
      • Roeselare, Belgium
        • Active, not recruiting
        • Research Facility
  • Brazil
      • Brasília, Brazil
        • Active, not recruiting
        • Research Facility
      • Rio de Janeiro, Brazil
        • Completed
        • Research Facility
      • São Paulo, Brazil
        • Active, not recruiting
        • Research Facility
  • Canada
    • Ontario
      • London, Ontario, Canada
        • Active, not recruiting
        • Research Facility
      • Toronto, Ontario, Canada, M4N 3M5
        • Active, not recruiting
        • Research Facility
    • Quebec
      • Montreal, Quebec, Canada
        • Active, not recruiting
        • Research Facility
  • France
      • Clichy, France
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Lille, France
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Montpellier, France
        • Active, not recruiting
        • Research Facility
      • Nantes, France
        • Active, not recruiting
        • Research Facility
      • Vandœuvre-lès-Nancy, France
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Villejuif, France
        • Active, not recruiting
        • Research Facility
  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Maastricht, Netherlands
        • Active, not recruiting
        • Research Facility
      • Utrecht, Netherlands
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
  • South Korea
      • Seoul, South Korea
        • Active, not recruiting
        • Research Facility
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Madrid, Spain
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Zaragoza, Spain
        • Completed
        • Research Facility
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Active, not recruiting
        • Research Facility
    • California
      • Duarte, California, United States, 91010
        • Completed
        • Research Facility
      • Irvine, California, United States, 92663
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Los Angeles, California, United States, 90095
        • Active, not recruiting
        • Research Facility
      • Palo Alto, California, United States, 94305
        • Active, not recruiting
        • Research Facility
      • San Francisco, California, United States, 94143
        • Active, not recruiting
        • Research Facility
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Active, not recruiting
        • Research Facility
    • District of Columbia
      • Washington D.C., District of Columbia, United States, 20010
        • Active, not recruiting
        • Research Facility
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Active, not recruiting
        • Research Facility
      • Miami, Florida, United States, 33165
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • Tampa, Florida, United States, 33607
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Active, not recruiting
        • Research Facility
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Maryland
      • Glen Burnie, Maryland, United States, 21061
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Active, not recruiting
        • Research Facility
      • Boston, Massachusetts, United States, 02118
        • Active, not recruiting
        • Research Facility
    • Michigan
      • Troy, Michigan, United States, 48098
        • Completed
        • Research Facility
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Active, not recruiting
        • Research Facility
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
      • New York, New York, United States, 10029
        • Active, not recruiting
        • Research Facility
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Active, not recruiting
        • Research Facility
      • Columbus, Ohio, United States, 43221
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Oregon
      • Portland, Oregon, United States, 97239
        • Active, not recruiting
        • Research Facility
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Active, not recruiting
        • Research Facility
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Active, not recruiting
        • Research Facility
    • Texas
      • Houston, Texas, United States, 77030
        • Active, not recruiting
        • Research Facility
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact
    • Washington
      • Seattle, Washington, United States, 98109
        • Recruiting
        • Research Facility
        • Contact:
          • Site Contact

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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
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, 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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1b: Cmax
Time Frame: Up to Day 8
Up to Day 8
Phase 1b: Tmax
Time Frame: Up to Day 8
Up to Day 8
Phase 1b: AUC
Time Frame: Up to Day 8
Up to Day 8
Phase 1b: Volume of Distribution
Time Frame: Up to Day 8
Up to Day 8
Phase 1b: Clearance
Time Frame: Up to Day 8
Up to Day 8
Phase 1b: Terminal Half-life
Time Frame: Up to Day 8
Up to Day 8
Phase 1b: TIAC of RYZ101 to critical organs and tumors
Time Frame: Up to Day 184
Calculated mean TIAC (hours) and absorbed radiation dose coefficients (mGy/MBq) to critical organs (e.g., the kidneys and bone marrow) and tumors after the 1st and 4th RYZ101 infusions will be assessed
Up to Day 184
Phase 1b: Absorbed radiation doses of RYZ101 to critical organs and tumors
Time Frame: Up to Day 184
Calculated mean TIAC (hours) and absorbed radiation dose coefficients (mGy/MBq) to critical organs (e.g., the kidneys and bone marrow) and tumors after the 1st and 4th RYZ101 infusions will be assessed
Up to Day 184
Phase 3: OS
Time Frame: Up to 80 months or until a total of 130 deaths have occurred, whichever occurs first
OS will be defined as the time from the date of randomization until the date of death due to any cause.
Up to 80 months or until a total of 130 deaths have occurred, whichever occurs first
Phase 3: ORR by BICR
Time Frame: Up to 80 months
ORR, as determined by BICR according to RECIST v1.1.
Up to 80 months
Phase 3: PFS
Time Frame: Up to 80 months
PFS as determined by Investigator
Up to 80 months
Phase 3: ORR by Inv
Time Frame: Up to 80 months
ORR, as assessed by the Investigator according to RECIST v1.1
Up to 80 months
Phase 3: BOR
Time Frame: Up to 80 months
Assessed by BICR and by the Investigator according to RECIST v1.1
Up to 80 months
Phase 3: Disease Control Rate
Time Frame: Up to 80 months
Assessed by BICR and by the Investigator according to RECIST v1.1
Up to 80 months
Phase 3: DoR
Time Frame: Up to 80 months
Only for subjects with a RECIST v.1.1 response, assessed by BICR and by the Investigator according to RECIST v1.1
Up to 80 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Phase 1b and 3: Incidence and severity of AEs by NCI CTCAE v5, including SAEs, laboratory changes, ECG changes, and other safety findings
Time Frame: Up to 80 months
Incidence and severity of AEs by NCI CTCAE v5, including SAEs, laboratory changes, ECG changes, and other safety findings
Up to 80 months
Phase 3: Cmax
Time Frame: Up to 80 months
Up to 80 months
Phase 3: AUC
Time Frame: Up to 80 months
Up to 80 months
Phase 3: Average Concentration
Time Frame: Up to 80 months
Up to 80 months
Phase 3: Relationship between exposure endpoints and clinical outcomes
Time Frame: Up to 80 months
Up to 80 months
Phase 3: Relationship between biomarkers including but not limited to CgA in the serum and (5-HIAA) in the urine, with AEs of special interest and/or efficacy endpoints (e.g., PFS, OS, BOR, DoR)
Time Frame: Up to 80 months
Relationship between biomarkers, including but not limited to CgA in the serum and (5-HIAA) in the urine, with AEs of special interest and/or efficacy endpoints (e.g., PFS, OS, BOR, DoR)
Up to 80 months
Phase 3: Changes in EQ-5D-5L questionnaire scores
Time Frame: Up to 80 months
Up to 80 months
Phase 3: Changes in EORTC QLQ-C30 questionnaire scores
Time Frame: Up to 80 months
Up to 80 months
Phase 3: Changes in EORTC QLQ GI NET21 questionnaire scores
Time Frame: Up to 80 months
Up to 80 months
Phase 3: QTc
Time Frame: Up to 80 months
Measured by continuous ECG recording using a 12-lead Holter monitoring device
Up to 80 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
RayzeBio, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • 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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 24, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 20, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 25, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 28, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 30, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 27, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

product manufactured in and exported from the U.S.

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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