A Phase I/II, Dose Finding and Optimization Study of [177Lu]Lu-NeoB in Combination With Capecitabine in Patients With GRPR+, ER+, HER2- Metastatic Breast Cancer After Progression on Previous Endocrine Therapy in Combination With a CDK4/6 Inhibitor.

Despite remarkable clinical results with the use of CDK4/6i, breast cancer patients will experience progression of disease requiring alternative treatment options. The optimal sequence of therapy after progression on CDK4/6i has not been established and it depends on multiple factors, including previous regimens, mutational profile, comorbidities, patient preference or disease burden (NCCN v4, 2023). Thus, new targeted treatment modalities are needed for treatment of patients with endocrine-resistant mBC.

The purpose of this Phase I/II study conducted in participants with ER+/HER2-, gastrin releasing peptide receptor positive (GRPR+) mBC after progression on CDK4/6i-based therapy is:

In the Phase I (dose escalation part) to determine the recommended doses and regimens of \[177Lu\]Lu-NeoB in combination with capecitabine in post-menopausal women and men not requiring gonadotropin releasing hormone agonist.

In the Phase II (dose optimization part) to evaluate preliminary efficacy across 2 different dose levels and regimens of \[177Lu\]Lu-NeoB in combination with capecitabine in adults including pre/peri-menopausal and post-menopausal women, and men, regardless of their need of a gonadotropin releasing hormone agonist (GnRha).

During screening, study participants will receive the radioligand imaging agent \[68Ga\]Ga-NeoB for a positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI). An additional \[68Ga\]Ga-NeoB for PET/CT or PET/MRI will be performed after their last administration of \[177Lu\]Lu-NeoB for phase II participants only.

During the treatment period participants will be required to attend a site visit approximately every 3 weeks for the first 9 months and every 6 weeks thereafter, on the first day of every cycle (defined as a period of 3 weeks) or every other cycle, respectively, to undergo study treatment administration or dispensing, dosimetry and safety assessments. Tumor assessments are performed every 9 weeks (+/- 7 days) until M18, then every 12 weeks until M36, and thereafter as clinically indicated until documented disease progression, death, withdrawal of consent, loss to follow-up, participant/guardian decision. After study treatment discontinuation, participants will be followed up for safety for 8 weeks after their last study treatment administration. Beyond the initial 8 weeks of safety follow-up, all participants will be followed up as per the Schedule of Assessments, for a total of 5 years from their last \[177Lu\]Lu-NeoB administration, or until death, lost to follow-up, participant/guardian's or investigator's decision or withdrawal of consent (WoC).