Phase 1b/2 open-label trial of 225Ac-DOTATATE (RYZ101) alone and in combination with pembrolizumab 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) and progressed after antibody-drug conjugates and/or chemotherapy (TRACY-1).

Study of an Investigational Medication for Advanced Breast Cancer

K
Kathy Miller, MD

Primary Investigator

Recruiting
18 years - 100 years
All
Phase 1/2
3 participants needed
1 Location

Brief description of study

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

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:

IU Clinical Trials Office 

Email: iutrials@iu.edu 

Phone: (317) 278-5632

Detailed description of study

Primary
Dose Escalation: To determine the RP2D of RYZ101, in subjects with refractory ER+, HER2-negative ABC Randomization: To determine the optimal treatment regimen of RYZ101, alone or in combination with pembrolizumab, in subjects with refractory ER+, HER2-negative ABC Expansion: To determine the efficacy of RYZ101 at the optimal treatment regimen in terms of ORR by BICR in subjects with refractory ER+, HER2-negative ABC

Secondary
To further evaluate the efficacy of RYZ101 alone and in combination withbrolizumab in terms of other Investigator-assessed efficacy endpoints in subjects with refractory ER+, HER2-negative ABC To characterize the safety and tolerability of RYZ101 administered every 6 weeks for up to 6 cycles, alone and in combination with pembrolizumab To determine the efficacy of RYZ101 alone and in combination with pembrolizumab in terms of OS in subjects with refractory ER+, HER2-negative ABC To further evaluate the efficacy of RYZ101 at the optimal treatment regimen in terms of other efficacy endpoints as assessed by BICR in subjects with refractory ER+, HER2-negative ABC

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: ER+ Breast Cancer, HER2-negative Breast Cancer, Metastatic Breast Cancer
  • Age: 18 years - 100 years
  • Gender: All

Inclusion Criteria

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

  • Eastern Cooperative Oncology Group performance status ≤2.
  • Histologically confirmed, ER+, HER2-negative, locally advanced and unresectable or metastatic breast cancer not amenable to treatment with curative intent.
  • At least one RECIST v1.1-measurable tumor lesion that is SSTR-PET positive (defined as maximum standard uptake value (SUVmax) higher than liver mean standard uptake value (SUVmean) on SSTR-PET imaging) and at least 80% of RECIST v1.1measurable tumor lesions are SSTR-PET positive
  • Sufficient renal function, as evidenced by eGFR ≥60 mL/min/1.73m2 calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
  • Adequate hematologic and hepatic function

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 lactation.

This study investigates an investigational medication for people with advanced breast cancer. Breast cancer can be classified based on certain receptors, like estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 (HER2)-negative. This study focuses on those with these types of breast cancer that have also progressed despite previous treatments. The investigational medication is being tested alone and in combination with another medicine to see how well it works and how safe it is.

Participants in this study will receive the investigational medication every 6 weeks for up to 6 cycles. The study will evaluate how the medicine affects the cancer and its safety. Participants will be closely monitored through various tests and assessments to understand the effects of the treatment. This helps researchers gather important information about the investigational medication.

  • Who can participate: Adults with ER+, HER2-negative advanced breast cancer that cannot be treated with curative intent may participate. They must have a tumor that is measurable and shows specific characteristics on imaging tests. Participants need to have good kidney, liver, and blood function.
  • Study details: Participants will receive the investigational medication. Some participants may also receive an additional medicine. The study will involve regular health checks and imaging to monitor the effects of the treatment.
Updated on 21 Oct 2025. Study ID: CTO-RYZ101-201, 22961

Find a site

We have submitted the contact information you provided to the research team at {{SITE_NAME}}. A copy of the message has been sent to your email for your records.
Would you like to be notified about other trials? Sign up for Patient Notification Services.
Sign up

Send a message

Enter your contact details to connect with study team

Investigator Avatar

Primary Contact

First name*
Last name*
Email*
Phone number*
Other language

Interested in the study?

Select a study center that’s convenient for you, and get in touch with the study team.

Connect with the Study Team