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).
Trial Snapshot
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- RayzeBio, Inc.
- Enrollment
- 16
- Locations
- 31
- Primary Endpoint
- Dose Escalation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts 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 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
Arms & Interventions
Dose Escalation
RYZ101 Dose Level -1
RYZ101 Dose Level 1
RYZ101 Dose Level 2
RYZ101 Dose Level 3
Intervention: RYZ101 (Drug)
Expansion
RYZ101 RP2D Regimen
Intervention: RYZ101 (Drug)
Outcomes
Primary Outcomes
Dose Escalation
Time Frame: 6 weeks of RYZ101 treatment
Incidence rate of DLTs during the first 6 weeks of RYZ101 treatment
Expansion
Time Frame: Up to approximately 5 years after the last subject has completed RYZ101 treatment
Overall Response Rate, defined as rate of subjects achieving a Complete Response or Partial Response as determined by BICR using RECIST v1.1
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
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
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
Secondary Outcomes
No secondary outcomes reported