Trial of 225Ac-DOTATATE (RYZ101) Alone and with Pembrolizumab in Subjects with ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs

Trial Title: Trial of 225Ac-DOTATATE (RYZ101) Alone and with Pembrolizumab in Subjects with ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs

NCT ID: NCT06590857

Condition: Metastatic Breast Cancer
HER2-negative Breast Cancer
ER+ Breast Cancer

Conditions: Official terms:
Breast Neoplasms
Pembrolizumab

Conditions: Keywords:
Actinium
Alpha-Emitter
SSTR+ MBC
ER+, HER2-, MBC
RYZ101
225Ac
Targeted Radiotherapy
Radiopharmaceutical

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: RYZ101
Description: Ac-225
Arm group label: Dose Escalation
Arm group label: Expansion
Arm group label: Randomization

Intervention type: Drug
Intervention name: Pembrolizumab
Description: Keytruda
Arm group label: Expansion
Arm group label: Randomization

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

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Eastern Cooperative Oncology Group Performance Status of ≤ 2 - Histologically confirmed, ER+ (defined as ≥1% of tumor cells staining positive for ER on IHC, or if no percentage is available, then an Allred IHC score of ≥3/8), HER2-negative (defined as IHC score of 0 or 1, or IHC score of 2 with negative ISH) 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 v1.1 measurable tumor lesions are SSTR-PET positive within 90 days of enrollment. - Sufficient renal function, as evidenced by creatinine clearance (CrCl) ≥60 mL/min calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation - Adequate hematologic, hepatic and coagulation function Exclusion Criteria: - History of severe hypersensitivity (Grade ≥3) to any of the components or excipients used in the study treatments or imaging agents. - Prior RPT, including radioembolization. - Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-PD L1, or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137). - Any toxicities from prior treatments that have not recovered to CTCAE Grade ≤1, except for alopecia. - Significant cardiovascular disease - Known brain, meningeal, or spinal cord metastases. Subjects with brain metastases may be eligible if asymptomatic, previously treated, and all brain lesions must have been controlled for at least 6 months prior to enrollment. Subjects with untreated brain lesions that are SSTR+ may be eligible after approval by the medical monitor. - History of hypersensitivity or allergy to pembrolizumab or any of its components, or 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. Other protocol-defined criteria may apply.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Research Facility

Address:
City: Indianapolis
Zip: 46202
Country: United States

Status: Recruiting

Contact:
Last name: Site Contact

Start date: July 19, 2024

Completion date: July 2029

Lead sponsor:
Agency: RayzeBio, Inc.
Agency class: Industry

Source: RayzeBio, Inc.

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06590857