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

The study comprises of a dose escalation part and, a concurrent backfill part. 1. The dose escalation part will estimate the RD of \[177Lu\]Lu-NeoB in combination with ribociclib and fulvestrant; four provisional dose levels are planned to be tested: 100 millicurie (mCi) (initial dose), 150mCi, 200 mCi and 250mCi in cohorts of 3 to 6 participants. After inclusion of each cohort of 3 to 6 participants, the incidence rate of DLTs will be compared to the pre-defined toxicity rate boundaries to decide whether the next cohort will receive a lower, higher or same dose or whether the trial will be terminated. 2. The backfill part will allow enrollment to a previously cleared dose level (during escalation part) in order to obtain additional safety, tolerability as well as preliminary efficacy data. During the backfill part, the cumulative incidence rate of DLTs will also be compared to the pre-defined toxicity rate boundaries to determine if escalation should be restarted from a lower dose level. 3. The recommended dose (RD) will be determined considering all available data from the escalation and backfill part. During screening, study participants will receive the investigational imaging agent \[68Ga\]Ga-NeoB. An additional administration of the \[68Ga\]Ga-NeoB will be performed potentially at Cycle 2 Day 15, and within 4-8 weeks from the last administration of \[177Lu\]Lu-NeoB for a positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI). Study treatment will include \[177Lu\]Lu-NeoB on day 1 of each 28-day cycle (+ =\< 3 days) for 6 cycles, ribociclib (once daily; days 1 to 21 in a 28-day cycle) and fulvestrant (C1D1, C1D15, C2D1 and every 28 days thereafter) until disease progression. Pre- and perimenopausal women and men will additionally receive goserelin on day 1 of every cycle. During the treatment period participants will be required to attend a site visit approximately every 28 days, on the first day of each cycle (as well as on C1D2, C1D3, C1D8, C1D15, C2D15, C3D3 and C5D3), to undergo study treatment administration, dosimetry and safety assessments. Radiologic tumor assessments (chest, abdomen, and pelvis CT or MRI) are performed every 8 weeks (± 7 days) until end of \[¹⁷⁷Lu\]Lu-NeoB treatment. After the end of \[¹⁷⁷Lu\]Lu-NeoB treatment, imaging assessments will be performed as clinically indicated at the discretion of the investigator. The end of study is defined as the date of the last visit, scheduled procedure or follow up (or date of death, WoC or lost to follow up, whichever occurs first) of the last participant in the study globally.