Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs. (TRACY-1)

August 20, 2026 updated by: RayzeBio, Inc.

Phase 1b/2 Open-label Trial of 225Ac-DOTATATE (RYZ101) in Subjects With Estrogen Receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)-Negative, Locally Advanced and Unresectable or Metastatic Breast Cancer Expressing Somatostatin Receptors (SSTRs) (TRACY-1).

Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) in subjects with ER+, HER2-negative unresectable or metastatic breast cancer expressing SSTRs.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

16

Phase

  • Phase 2
  • Phase 1

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

  • Canada
    • British Columbia
      • Victoria, British Columbia, Canada, V8R 6V5
        • Research Facility
    • Ontario
      • Toronto, Ontario, Canada, M4N 3M5
        • Research Facility
      • Toronto, Ontario, Canada, M5G 2M9
        • Research Facility
    • Quebec
      • Québec, Quebec, Canada, G1S 4L8
        • Research Facility
  • South Korea
    • Seoul
      • Seoul, Seoul, South Korea, 03080
        • Research Facility
      • Seoul, Seoul, South Korea, 05505
        • Research Facility
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Research Facility
    • California
      • Irvine, California, United States, 92618
        • Research Facility
      • San Diego, California, United States, 92093
        • Research Facility
      • Santa Monica, California, United States, 90404
        • Research Facility
    • Colorado
      • Longmont, Colorado, United States, 80504
        • Research Facility
    • Florida
      • Jacksonville, Florida, United States, 32224
        • Research Facility
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Research Facility
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Research Facility
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Research Facility
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Research Facility
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Research Facility
    • Missouri
      • St Louis, Missouri, United States, 63130
        • Research Facility
    • Nebraska
      • Omaha, Nebraska, United States, 68124
        • Research Facility
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Research Facility
    • New York
      • Buffalo, New York, United States, 14203
        • Research Facility
      • New York, New York, United States, 10016
        • Research Facility
      • New York, New York, United States, 10021
        • Research Facility
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Research Facility
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Research Facility
      • Pittsburgh, Pennsylvania, United States, 15213
        • Research Facility
    • Texas
      • Dallas, Texas, United States, 75246
        • Research Facility
      • Houston, Texas, United States, 77024
        • Research Facility
    • Utah
      • Salt Lake City, Utah, United States, 84132
        • Research Facility
    • Virginia
      • Norfolk, Virginia, United States, 23502
        • 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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

Subjects must meet all the following criteria for enrollment in the study:

  • Histologically confirmed, ER+, HER2-negative, locally advanced and unresectable or metastatic breast cancer not amenable to treatment with curative intent.
  • Adequate renal, hematologic, and hepatic function

  • Additional inclusion criteria for Monotherapy arm:

    • Measurable disease with at least 80% SSTR-positive lesions by SSTR-PET imaging
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤2
    • Documented radiologic progression after at least 2 and no more than 4 prior chemotherapy or ADC regimens in the metastatic setting

  • Additional inclusion criteria for ET Combination arms:

    • Prior treatment with CDK4/6 inhibitors in combination with endocrine therapy in the advanced or metastatic setting.
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
    • Bone only or bone dominant disease. At least 1 bone lesion must be SSTR-positive on SSTR-PET imaging. For bone dominant disease, at least 50% of soft tissue measurable lesions must be SSTR-positive on SSTR-PET imaging. At least one bone lesion must be positive on both SSTR-PET and on FDG-PET imaging
    • Brain metastases are allowed if definitively treated and clinically stable as confirmed by interval imaging

Exclusion Criteria

Subjects who meet any of the following criteria will be excluded from the study:

  • Prior radiopharmaceutical therapy, including radioembolization.
  • Any toxicities from prior treatments that have not recovered to CTCAE Grade ≤1, except for alopecia.
  • Significant cardiovascular disease
  • Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, spinal cord compression, or leptomeningeal disease.
  • History of hypersensitivity or allergy to 225Ac, 68Ga, 64Cu, octreotate, or any of the excipients of DOTATATE imaging agents.
  • Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the study safety or efficacy assessments.
  • Pregnancy or breastfeeding

  • Additional exclusion criteria for ET Combination arms:

    • Presence of liver metastases or symptomatic metastatic visceral disease
    • Prior PARPi exposure or are candidates for PARPi per local guidelines

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: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Monotherapy Dose Escalation
Escalating doses of RYZ101 administered intravenously (IV)
Drug: RYZ101
Ac-225
Experimental: Endocrine Therapy Combination Dose Escalation and Expansion
RYZ101 in combination with investigator's choice of standard of care endocrine therapy
Drug: RYZ101
Ac-225
Drug: Standard of Care Endocrine Therapy
Investigator's choice of endocrine therapy, such as, anastrozole, elacestrant, exemestane, fulvestrant, imlunestrant, letrozole, tamoxifen, or vepdegestrant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Escalation
Time Frame: 6 weeks of RYZ101 treatment
Incidence rate of DLTs during the first 6 weeks of RYZ101 treatment
6 weeks of RYZ101 treatment
Endocrine Therapy Combination Dose Escalation
Time Frame: [Time Frame: 6 weeks of study treatment]
Incidence rate of DLTs during the first 6 weeks of study treatment
[Time Frame: 6 weeks of study treatment]
Endocrine Therapy Combination Dose Escalation
Time Frame: Up to approximately 5 years after the last subject has completed RYZ101 treatment
Incidence and severity of treatment emergent AEs by NCI-CTCAE v5.0
Up to approximately 5 years after the last subject has completed RYZ101 treatment
Endocrine Therapy Combination Dose Escalation and Expansion
Time Frame: Up to approximately 5 years after the last subject has completed RYZ101 treatment
Progression Free Survival, defined as the time between first dose of study treatment and progression or death, as assessed by the investigator per RECIST v1.1 criteria
Up to approximately 5 years after the last subject has completed RYZ101 treatment
Endocrine Therapy Combination Dose Escalation and Expansion
Time Frame: Up to approximately 5 years after the last subject has completed RYZ101 treatment
Time from the first dose of study treatment to first occurrence of Skeletal Related Events
Up to approximately 5 years after the last subject has completed RYZ101 treatment

Collaborators and Investigators

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

Sponsor

RayzeBio, Inc.

Investigators

  • Study Director: Petrus de Jong, MD, PhD, RayzeBio, Inc.

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)

July 19, 2024

Primary Completion (Estimated)

October 1, 2028

Study Completion (Estimated)

November 1, 2033

Study Registration Dates

First Submitted

September 3, 2024

First Submitted That Met QC Criteria

September 10, 2024

First Posted (Actual)

September 19, 2024

Study Record Updates

Last Update Posted (Actual)

August 24, 2026

Last Update Submitted That Met QC Criteria

August 20, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RYZ101-201

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.

Subscribe