Metastatic Breast Cancer, HER2-negative Breast Cancer, ER+ Breast Cancer, Advanced Breast Cancer, Metastatic Breast Cancer With Bone Involvement, Bone Metastases in Subjects With Advanced Breast Cancer, ER-Positive HER2-Negative Breast Cancer, Estrogen Receptor-positive Breast Cancer, Hormone-sensitive Metastatic Breast Cancer, Hormone-Sensitive Breast Cancer
Conditions
Keywords
Actinium, Alpha-Emitter, SSTR+ MBC, ER+, HER2-, MBC, RYZ101, 225Ac, Targeted Radiotherapy, Radiopharmaceutical, SSTR+ ABC, ER+, HER2-, ABC
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.
Interventions
DRUGRYZ101
Ac-225
DRUGStandard of Care Endocrine Therapy
Investigator's choice of endocrine therapy, such as, anastrozole, elacestrant, exemestane, fulvestrant, imlunestrant, letrozole, tamoxifen, or vepdegestrant
Sponsors
RayzeBio, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Escalation | 6 weeks of RYZ101 treatment | Incidence rate of DLTs during the first 6 weeks of RYZ101 treatment |
| Endocrine Therapy Combination Dose Escalation | [Time Frame: 6 weeks of study treatment] | Incidence rate of DLTs during the first 6 weeks of study treatment |
| Endocrine Therapy Combination Dose Escalation and Expansion | 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 |
Countries
Canada, South Korea, United States
Contacts
STUDY_DIRECTORPetrus de Jong, MD, PhD
RayzeBio, Inc.
Outcome results
None listed