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.
