NCT05870579

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

A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With Estrogen Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative and Gastrin Releasing Peptide Receptor Positive Advanced Breast Cancer Experiencing Early Relapse From (Neo)Adjuvant Endocrine Therapy or Who Have Progressed on Endocrine Therapy in Combination With a CDK4/6 Inhibitor for Advanced Disease

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 18 Years – 100 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this trial is to estimate the recommended dose (RD) of \[177Lu\]Lu-NeoB in combination with ribociclib and fulvestrant in participants with estrogen receptor (ER) positive (ER+), human epidermal growth factor receptor-2 (HER2) negative (HER2-) and gastrin releasing peptide receptor (GRPR) positive (GRPR+) advanced breast cancer experiencing early relapse from (neo)adjuvant endocrine therapy or who have progressed on endocrine therapy in combination with a CDK4/6 inhibitor for advanced disease.

Detailed description

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. Tumor assessments are performed every 8 weeks until month 18, every 12 weeks until month 36 and as clinically indicated thereafter, until disease progression. 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 every 12 weeks until month 36 and every 24 weeks thereafter until month 60 for a total of 5 years from the participant's enrollment in the study, or until death, lost to follow-up, or withdrawal of consent (WoC), whichever occurs first. 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, or at 5 years from the date of the last participant enrolled, whichever occurs earlier.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DRUG	[68Ga]Ga-NeoB	\[68Ga\]Ga-NeoB serves as a radioactive imaging compound to be used for PET imaging for localization of GRPR positive lesions, at screening, potentially at Cycle 2 Day 15 visit, and between 4 and 8 weeks after the last administered dose of \[177Lu\]Lu-NeoB. \[68Ga\]Ga-NeoB will be administered as a single intravenous (i.v.) dose.
DRUG	[177Lu]Lu-NeoB	Study participants will receive \[177Lu\]Lu-NeoB once every cycle
DRUG	Ribociclib	600 mg once daily (OD) days 1 to 21 every 28 days
DRUG	Fulvestrant	500 mg at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and every 28 days thereafter
OTHER	Goserelin	For pre/peri-menopausal women and men only.

Timeline

• Start date: 2023-11-13
• Primary completion: 2026-12-30
• Completion: 2032-01-26
• First posted: 2023-05-23
• Last updated: 2025-08-21

Locations

25 sites across 7 countries: United States, China, France, Germany, Poland, Portugal, Spain

Regulatory

• FDA-regulated drug study