Recruiting
Phase 1
Phase 2

225Ac-DOTATATE

Sponsor:

RayzeBio, Inc.

Code:

NCT06590857

Conditions

Metastatic Breast Cancer

HER2-negative Breast Cancer

ER+ Breast Cancer

Advanced Breast Cancer

Metastatic Breast Cancer With Bone Involvement

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

Interventions

RYZ101

Standard of Care Endocrine Therapy

Study Details

Brief summary:

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

Conditions

Metastatic Breast Cancer

HER2-negative Breast Cancer

ER+ Breast Cancer

Advanced Breast Cancer

Metastatic Breast Cancer With Bone Involvement

Study ID

NCT06590857

Start date

Jul 19, 2024

Status verified date

Oct, 2026

Completion date

Nov, 2033

Anticipated

Primary completion date

Oct, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0+

Healthy Volunteers: Not accepted

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 Design

Enrollment

64 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Monotherapy Dose Escalation

Escalating doses of RYZ101 administered intravenously (IV)

experimental: Endocrine Therapy Combination Dose Escalation and Expansion

RYZ101 in combination with investigator's choice of standard of care endocrine therapy

Interventions

RYZ101

Ac-225

Standard of Care Endocrine Therapy

Investigator's choice of endocrine therapy, such as, anastrozole, elacestrant, exemestane, fulvestrant, imlunestrant, letrozole, tamoxifen, or vepdegestrant

Primary outcome measure

  • Dose Escalation [ Time Frame: 6 weeks of RYZ101 treatment ]
  • Endocrine Therapy Combination Dose Escalation [ Time Frame: [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 ]
  • Endocrine Therapy Combination Dose Escalation and Expansion [ Time Frame: 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 ]

Central Contacts and Locations

Central contacts

RayzeBio Clinical Trials

1-619-657-0057clinicaltrials@rayzebio.com

Locations

Research Facility

Recruiting

Omaha, Nebraska, United States, 68124

More Information

Sponsor

RayzeBio, Inc.

Last update posted

Oct 6, 2026

Last verified

Oct, 2026

Keywords

  • Actinium
  • Alpha-Emitter
  • SSTR+ MBC
  • ER+, HER2-, MBC
  • RYZ101
  • 225Ac
  • Targeted Radiotherapy
  • Radiopharmaceutical
  • SSTR+ ABC
  • ER+, HER2-, ABC

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-07. This information was provided to ClinicalTrials.gov by RayzeBio, Inc. on 2026-10-06. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.