Clinical trial NCT06590857: Trial of 225Ac-DOTATATE (RYZ101) in Subjects with ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.
Official title: 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) and Progressed After Antibody-drug Conjugates And/or Chemotherapy (TRACY-1).
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Metastatic Breast Cancer
HER2-negative Breast Cancer
ER+ Breast Cancer
Advanced Breast Cancer
Keywords: Actinium
Alpha-Emitter
SSTR+ MBC
ER+, HER2-, MBC
RYZ101
225Ac
Targeted Radiotherapy
Radiopharmaceutical
SSTR+ ABC
ER+, HER2-, ABC
Lead sponsor: RayzeBio, Inc.
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Dose Escalation
timeFrame: 6 weeks of RYZ101 treatment
measure: Expansion
timeFrame: Up to approximately 5 years after the last subject has completed RYZ101 treatment
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Research Facility
state: Arizona
city: Irvine
country: United States
facility: Research Facility
state: California
city: Santa Monica
country: United States
facility: Research Facility
state: California
city: Longmont
country: United States
facility: Research Facility
state: Colorado
city: Jacksonville
country: United States
facility: Research Facility
state: Florida
city: Atlanta
country: United States
facility: Research Facility
state: Georgia
city: Indianapolis
country: United States
facility: Research Facility
state: Indiana
city: Boston
country: United States
facility: Research Facility
state: Massachusetts
city: Detroit
country: United States
facility: Research Facility
state: Michigan
city: Rochester
country: United States
facility: Research Facility
state: Minnesota
city: Saint Louis
country: United States
facility: Research Facility
state: Missouri
city: Omaha
country: United States
facility: Research Facility
state: Nebraska
city: Buffalo
country: United States
facility: Research Facility
state: New York
city: New York
country: United States
facility: Research Facilty
state: New York
city: New York
country: United States
facility: Research Facility
state: New York
city: Cleveland
country: United States
facility: Research Facility
state: Ohio
city: Philadelphia
country: United States
facility: Research Facility
state: Pennsylvania
city: Pittsburg
country: United States
facility: Research Facility
state: Pennsylvania
city: Dallas
country: United States
facility: Research Facility
state: Texas
city: Houston
country: United States
facility: Research Facility
state: Texas
city: Salt Lake City
country: United States
facility: Research Facilty
state: Utah
city: Norfolk
country: United States
facility: Research Facility
state: Virginia
city: Seattle
country: United States
facility: Research Facility
state: Washington
Study officials:
affiliation: RayzeBio, Inc.
name: Denis Ferreira, MD
role: STUDY_DIRECTOR
References: