Radioactive cocktail targets Hard-to-Treat breast cancer

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Key Inclusion criteria: * Adult female or male \>= 18 years of age at the time of informed consent * Histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive with ER \>10% (regardless of progesterone receptor (PgR) expression) breast cancer by local laboratory testing (based on the most recently analyzed tissue sample) * HER2 negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (e.g. fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH), or silver in situ hybridization (SISH)) test is required by local laboratory testing (based on the most recently analyzed tissue sample) * Participant has advanced (loco regionally recurrent not amenable to curative therapy (e.g. surgery and/or radiotherapy) or metastatic) breast cancer Participants may be: 1. relapsed with documented evidence of relapse on or within 12 months from completion of (neo)adjuvant endocrine therapy (+/- CDK4/6 inhibitor) with no treatment for advanced disease OR 2. relapsed with documented evidence of relapse more than 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression after one line of endocrine therapy (except fulvestrant) (+/- CDK4/6 inhibitor) for advanced disease OR 3. advanced breast cancer at diagnosis that progressed with documented evidence of progression after one line of endocrine therapy (except fulvestrant) (+/- CDK4/6 inhibitor) Note: Participant who relapsed with documented evidence of relapse on/or within 12 months from completion of (neo)adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor) for advanced disease will NOT be included in the study. At least one target lesion (i.e., a measurable lesion as per RECIST 1.1) in the baseline stand-alone CT or MRI, showing \[68Ga\]Ga-NeoB uptake on PET/CT or PET/MRI scoring 2 or higher, based on the Visual Scoring Scale. * Adequate bone marrow and organ function as defined by the laboratory values. * Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed locally: * QT interval corrected by Fridericia's formula (QTcF) interval at screening \< 450 msec * Mean resting heart rate 50-90 bpm (determined from the ECG) * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Key Exclusion criteria: * More than one line of prior treatment in the advanced/metastatic setting. Participant shouldn't have received prior fulvestrant treatment. * Documented evidence of prior ribociclib dose reduction due to safety reasons either in adjuvant setting or for advanced disease. * Relapse or disease progression within 6 months of receiving a CDK4/6 inhibitor therapy either in adjuvant setting or for advanced disease. Symptomatic visceral disease or any disease burden that makes the participant ineligible for ribociclib plus endocrine treatment per the Investigator's best judgment. * Presence of central nervous system (CNS) involvement unless meeting BOTH of the following criteria: 1) At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment. 2) Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases. * Currently receiving warfarin or other Coumadin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin, or fondaparinux is allowed. * Diagnosis of inflammatory breast cancer at screening * Child Pugh score B or C * History or current diagnosis of impaired cardiac function, clinically significant cardiac disease or ECG abnormalities indicating significant risk of safety for participants. * Known or expected hypersensitivity to any of the study drugs or any of their excipients. * Prior administration of a radiopharmaceutical unless 10 or more half-lives have elapsed before injection of \[68Ga\]Ga-NeoB or \[177Lu\]Lu-NeoB * Participant has received extended-field RT=\< 4 weeks or limited field RT=\< 2 weeks prior to start of treatment and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the participant at Investigator's discretion) and/or prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow. * Participant is currently receiving or has received systemic corticosteroids =\< 2 weeks prior to starting study treatment, or who have not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular) * Participant has a history of or ongoing acute pancreatitis within 1 year of screening. * Participant is currently receiving any of the following substances and cannot be discontinued 7 days prior to starting study treatment: * Concomitant medications, herbal supplements, and/or fruits (e.g., grapefruit, pummelos, star fruit, Seville oranges) and their juices that are strong inducers or inhibitors of cytochrome P450 (CYP) 3A4 * Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 * Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointes (TdP) that cannot be discontinued or replaced by safe alternative medication (e.g., within 5 half-lives or 7 days prior to starting study treatment) * Participant is currently receiving NEP inhibitors (e.g.Entresto®, racecadotril) and images for dosimetry assessments cannot be acquired for this participant. Other protocol-defined inclusion/exclusion criteria may apply.