[177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With ER+, HER2- and GRPR+ Advanced Breast Cancer

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-receptorpositive with ER >10% (regardless of progesterone receptor (PgR) expression) breastcancer by local laboratory testing (based on the most recently analyzed tissuesample)

• HER2 negative breast cancer defined as a negative in situ hybridization test or animmunohistochemistry (IHC) status of 0, 1+ or 2+. If IHC is 2+, a negative in situhybridization (e.g. fluorescence in situ hybridization (FISH), chromogenic in situhybridization (CISH), or silver in situ hybridization (SISH)) test is required bylocal 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 completionof (neo)adjuvant endocrine therapy (+/- CDK4/6 inhibitor) with no treatment foradvanced 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 documentedevidence 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 ofprogression after one line of endocrine therapy (except fulvestrant) (+/- CDK4/6inhibitor) Note: Participant who relapsed with documented evidence of relapse on/orwithin 12 months from completion of (neo)adjuvant endocrine therapy and thensubsequently progressed with documented evidence of progression after one line ofendocrine therapy (with either an antiestrogen or an aromatase inhibitor) foradvanced 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 theVisual 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 andassessed 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 eitherin adjuvant setting or for advanced disease.

• Relapse or disease progression within 6 months of receiving a CDK4/6 inhibitortherapy either in adjuvant setting or for advanced disease. Symptomatic visceraldisease or any disease burden that makes the participant ineligible for ribociclibplus endocrine treatment per the Investigator's best judgment.

• Presence of central nervous system (CNS) involvement unless meeting BOTH of thefollowing criteria: 1) At least 4 weeks from prior therapy completion (includingradiation and/or surgery) to starting the study treatment. 2) Clinically stable CNStumor at the time of screening and not receiving steroids and/or enzyme inducinganti-epileptic medications for brain metastases.

• Currently receiving warfarin or other Coumadin derived anti-coagulant, fortreatment, prophylaxis or otherwise. Therapy with heparin, low molecular weightheparin, 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 significantcardiac disease or ECG abnormalities indicating significant risk of safety forparticipants.

• Known or expected hypersensitivity to any of the study drugs or any of theirexcipients.

• Prior administration of a radiopharmaceutical unless 10 or more half-lives haveelapsed before injection of [68Ga]Ga-NeoB or [177Lu]Lu-NeoB

• Participant has received extended-field RT=< 4 weeks or limited field RT=< 2 weeksprior to start of treatment and has not recovered to grade 1 or better from relatedside effects of such therapy (with the exception of alopecia or other toxicities notconsidered a safety risk for the participant at Investigator's discretion) and/orprior external beam radiation therapy (EBRT) to more than 25% of the bone marrow.

• Participant is currently receiving or has received systemic corticosteroids =< 2weeks prior to starting study treatment, or who have not fully recovered from sideeffects of such treatment. Note: The following uses of corticosteroids arepermitted: 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 ofscreening.

• Participant is currently receiving any of the following substances and cannot bediscontinued 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 orinhibitors of cytochrome P450 (CYP) 3A4

• Medications that have a narrow therapeutic window and are predominantly metabolizedthrough CYP3A4/5

• Concomitant medication(s) with a known risk to prolong the QT interval and/or knownto cause Torsades de Pointes (TdP) that cannot be discontinued or replaced by safealternative medication (e.g., within 5 half-lives or 7 days prior to starting studytreatment)

• Participant is currently receiving NEP inhibitors (e.g.Entresto®, racecadotril) andimages for dosimetry assessments cannot be acquired for this participant.

Other protocol-defined inclusion/exclusion criteria may apply.