Breast CancerPhase 1NCT05870579
[177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With ER+, HER2- and GRPR+ Advanced Breast Cancer
A Phase 1 study testing [68Ga]Ga-NeoB, [177Lu]Lu-NeoB and Ribociclib in people with Breast Cancer, run by Novartis Pharmaceuticals at 13 sites in 7 countries.
Trial 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+)… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Breast Cancer
- What is being tested?
- [68Ga]Ga-NeoB, [177Lu]Lu-NeoB and Ribociclib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 13 sitesin 7 countries
- Study dates
- 13 Nov 2023to 27 May 2032
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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
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- 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
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
13 sites in 7 countries.
13 sites in 7 countries
Spain4 sites
Novartis Investigative Site
Barcelona, 08036
Novartis Investigative Site
L'Hospitalet de Llobregat, Barcelona, 08907
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Madrid, 28040
France3 sites
Novartis Investigative Site
Bordeaux, 33076
Novartis Investigative Site
Saint-Cloud, Hauts De Seine, 92210
Novartis Investigative Site
Saint-Herblain, 44805
United States2 sites
MD Anderson Cancer Center
Houston, Texas, 77030
UCLA Jonsson Comp Cancer Center
Los Angeles, California, 90095
Germany1 site
Novartis Investigative Site
Cologne, North Rhine-Westphalia, 50937
About this study
Official title: 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
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.
Read the detailed description
The study comprises of a dose escalation part and, a concurrent backfill part.
- 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.
- 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.
- 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.
- Conditions
- Breast Cancer
- Being tested
- [68Ga]Ga-NeoB, [177Lu]Lu-NeoB, Ribociclib, Fulvestrant, Goserelin
- Keywords
- Advanced breast cancer, Radioligand therapy, Ribociclib, Fulvestrant, Lutetium, NeoB, Estrogen receptor (ER), ER-positive, Human epidermal growth factor 2 (HER2), HER-2 negative, Gastrin releasing peptide receptor (GRPR), GRPR-positive breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[68Ga]Ga-NeoBDrug
Also called gallium 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.
[177Lu]Lu-NeoBDrug
Also called lutetium neoB
Study participants will receive [177Lu]Lu-NeoB once every cycle
RibociclibDrug
Also called kisqali
600 mg once daily (OD) days 1 to 21 every 28 days
FulvestrantDrug
500 mg at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and every 28 days thereafter
GoserelinOther
Also called zoladex
For pre/peri-menopausal women and men only.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Participants will receive [177Lu]Lu- NeoB in combination with ribociclib and fulvestrant, in the dose escalation and the backfill parts of the study. Goserelin administration is only applicable for pre/peri-menopausal women and men. Receives: Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-NeoB; Drug: Ribociclib; Drug: Fulvestrant; Other: Goserelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and nature of DLTs during the DLT observation period
A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the DLT period from C1D1 of treatment with [177Lu]Lu-NeoB, ribociclib and fulvestrant with or without goserelin. The National Cancer Institute (NCI) CTCAE version 5.0 will be used for all grading.
Measured: 28 days after the first administration of [177Lu]Lu-NeoB
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Measured: From date of enrollment till 8 weeks after end of Treatment, assessed up to approximately 60 months
Incidence of dose interruptions, discontinuation and dose reductions
Dose interruptions, discontinuation and dose reductions will be assessed for tolerability.
Measured: From date of enrollment till 8 weeks after end of Treatment, assessed up to approximately 60 months
Secondary outcomes (16)
Time activity curves (TACs) of [177Lu]Lu-NeoB in organs and tumor lesions
Time activity curves (TACs) for the various organs and lesions will be produced as percentage of injected dose in selected organs and lesions.
Measured: Cycles 1, 3 and 5: Day 1 (1-4 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i) (1 cycle = 4 weeks)
Absorbed radiation doses of [177Lu]Lu-NeoB in organs and tumor lesions
The absorbed dose in target organs will be summarized with descriptive statistics.
Measured: Cycles 1, 3 and 5: Day 1 (1-4 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i) (1 cycle = 4 weeks)
Concentration of [177Lu]Lu-NeoB in blood over time
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of [177Lu]Lu-NeoB. Blood concentration of [177Lu]Lu-NeoB will be summarized with descriptive statistics.
Measured: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Observed maximum blood concentration (Cmax) of [177Lu]Lu-NeoB
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of [177Lu]Lu-NeoB. Cmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-NeoB
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of [177Lu]Lu-NeoB. Tmax will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Area under the blood concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-NeoB
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of [177Lu]Lu-NeoB. AUClast will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-NeoB
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of [177Lu]Lu-NeoB. CL will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-NeoB
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of [177Lu]Lu-NeoB. Vz will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Terminal elimination half-life (T^1/2) of [177Lu]Lu-NeoB
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of [177Lu]Lu-NeoB. T^1/2 will be listed and summarized using descriptive statistics.
Measured: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Objective Response Rate (ORR)
Objective Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), as per local review and according to RECIST 1.1.
Measured: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 60 months
Duration of Response (DoR)
Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented radiographic progression or death due to any cause as per local review and according to RECIST 1.1.
Measured: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to approximately 60 months
Time to Response (TTR)
Time to response (TTR) is the time from the date of first dose of [177Lu]Lu-NeoB to the first documented response (CR or PR) according to RECIST 1.1.
Measured: From the date of first dose to the date of documented response (CR or PR), assessed up to approximately 60 months
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) or maintaining an overall response of Stable Disease (SD) for at least 24 weeks. CR, PR, and SD are defined as per local review according to RECIST 1.1.
Measured: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 60 months
Progression Free Survival (PFS)
Progression Free Survival (PFS) is defined as the time from the date of first dose of [177Lu]Lu-NeoB to the date of confirmed progression or death due to any cause. PFS will be assessed via local review according to RECIST 1.1.
Measured: From the date of first dose to the date of confirmed progression or death due to any cause, whichever comes first, assessed up to approximately 60 months
Overall Survival (OS)
Overall Survival (OS) is defined as the time from date of first dose of [177Lu]Lu-NeoB to date of death due to any cause.
Measured: From the date of first dose to date due to any cause, assessed up to approximately 60 months
Incidence and severity of AEs following [68Ga]Ga-NeoB administration
Incidence and severity of AEs following [68Ga]Ga-NeoB administration at screening will be done via the analysis of frequencies for Adverse Event (AEs), Serious Adverse Event (SAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Measured: 3 days after [68Ga]Ga-NeoB administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2023
- Study start13 Nov 2023
- Primary completion30 Dec 2026 (estimated)
- Study completion27 May 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05870579
- Sponsor's protocol ID
- CAAA603B12101
- Other IDs
- 2022-502465-18-00
- Status last verified
- Sep 2026
- First submitted
- 8 May 2023
- Last updated
- 11 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720.
PubMed 38753757
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT05870579
- Acronym / sponsor ID
- CAAA603B12101
- Conditions
- Breast Cancer
- Keywords
- Advanced breast cancer, Radioligand therapy, Ribociclib, Fulvestrant, Lutetium, NeoB, Estrogen receptor (ER), ER-positive
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 13 Nov 2023 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 27 May 2032 (estimated)
- First posted
- 23 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
- 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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: [68Ga]Ga-NeoB, Drug: [177Lu]Lu-NeoB, Drug: Ribociclib, Drug: Fulvestrant, Other: GoserelinParticipants will receive [177Lu]Lu- NeoB in combination with ribociclib and fulvestrant, in the dose escalation and the backfill parts of the study. Goserelin administration is only applicable for pre/peri-menopausal women and men. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
- 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
Key exclusion criteria (19 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [68Ga]Ga-NeoBAlso: gallium 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 | Arm 1 |
| [177Lu]Lu-NeoBAlso: lutetium neoBStudy participants will receive [177Lu]Lu-NeoB once every cycle | Drug | Arm 1 |
| RibociclibAlso: kisqali600 mg once daily (OD) days 1 to 21 every 28 days | Drug | Arm 1 |
| Fulvestrant500 mg at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and every 28 days thereafter | Drug | Arm 1 |
| GoserelinAlso: zoladexFor pre/peri-menopausal women and men only. | Other | Arm 1 |
Primary outcome
Incidence and nature of DLTs during the DLT observation period
Time frame: 28 days after the first administration of [177Lu]Lu-NeoB
A DLT is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the DLT period from C1D1 of treatment with [177Lu]Lu-NeoB, ribociclib and fulvestrant with or without goserelin. The National Cancer Institute (NCI) CTCAE version 5.0 will be used for all grading.
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: From date of enrollment till 8 weeks after end of Treatment, assessed up to approximately 60 months
The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Incidence of dose interruptions, discontinuation and dose reductions
Time frame: From date of enrollment till 8 weeks after end of Treatment, assessed up to approximately 60 months
Dose interruptions, discontinuation and dose reductions will be assessed for tolerability.
16 secondary outcomes
Time activity curves (TACs) of [177Lu]Lu-NeoB in organs and tumor lesions
Time frame: Cycles 1, 3 and 5: Day 1 (1-4 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i) (1 cycle = 4 weeks)
Absorbed radiation doses of [177Lu]Lu-NeoB in organs and tumor lesions
Time frame: Cycles 1, 3 and 5: Day 1 (1-4 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i) (1 cycle = 4 weeks)
Concentration of [177Lu]Lu-NeoB in blood over time
Time frame: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Observed maximum blood concentration (Cmax) of [177Lu]Lu-NeoB
Time frame: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Time of maximum observed drug concentration occurrence (Tmax) of [177Lu]Lu-NeoB
Time frame: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Area under the blood concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of [177Lu]Lu-NeoB
Time frame: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Total systemic clearance for intravenous administration (CL) of [177Lu]Lu-NeoB
Time frame: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Volume of distribution during the terminal phase following intravenous elimination (Vz) of [177Lu]Lu-NeoB
Time frame: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Terminal elimination half-life (T^1/2) of [177Lu]Lu-NeoB
Time frame: Cycle 1: Day 1 (Pre-dose (before start of infusion), At end of infusion, 0.5, 1, 2, 4 and 6 hours post-dose/post-infusion (p.i.)), Day 2 (24 hours p.i), Day 3 (48 hours p.i), Day 8 (168 hours p.i)
Objective Response Rate (ORR)
Time frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 60 months
Duration of Response (DoR)
Time frame: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up to approximately 60 months
Time to Response (TTR)
Time frame: From the date of first dose to the date of documented response (CR or PR), assessed up to approximately 60 months
Clinical Benefit Rate (CBR)
Time frame: From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 60 months
Progression Free Survival (PFS)
Time frame: From the date of first dose to the date of confirmed progression or death due to any cause, whichever comes first, assessed up to approximately 60 months
Overall Survival (OS)
Time frame: From the date of first dose to date due to any cause, assessed up to approximately 60 months
Incidence and severity of AEs following [68Ga]Ga-NeoB administration
Time frame: 3 days after [68Ga]Ga-NeoB administration
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2026.
- Derived from this study: PubMed 38753757Taunk NK, Escorcia FE, Lewis JS, Bodei L. Radiopharmaceuticals for Cancer Diagnosis and Therapy: New Targets, New Therapies-Alpha-Emitters, Novel Targets. Cancer J. 2024 May-Jun 01;30(3):218-223. doi: 10.1097/PPO.0000000000000720.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
13 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing [68Ga]Ga-NeoB, [177Lu]Lu-NeoB and Ribociclib in people with Breast Cancer, run by Novartis Pharmaceuticals at 13 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Spain, France, United States, China, Germany and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence and nature of DLTs during the DLT observation period (time frame: 28 days after the first administration of [177Lu]Lu-NeoB). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05870579, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.