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

NCT05870579 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CAAA603B121012022-502465-18-00
• Study Type: interventional
• Target: 48
• Locations: 7 countries
• Sites: 25

Brief 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.

Conditions

Breast Cancer

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

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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

  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

  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

  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

  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

  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)

Study Arms (1)

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.

Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-NeoB; Drug: Ribociclib; Drug: Fulvestrant; Other: Goserelin

Interventions

[68Ga]Ga-NeoB DRUG

\[68Ga\]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.

Also known as: gallium neoB

Arm 1

[177Lu]Lu-NeoB DRUG

Study participants will receive \[177Lu\]Lu-NeoB once every cycle

Also known as: lutetium neoB

Arm 1

Ribociclib DRUG

600 mg once daily (OD) days 1 to 21 every 28 days

Also known as: kisqali

Arm 1

Fulvestrant DRUG

500 mg at Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1 and every 28 days thereafter

Arm 1

Goserelin OTHER

For pre/peri-menopausal women and men only.

Also known as: zoladex

Arm 1

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (25)

UCLA Jonsson Comp Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

University of Kansas Medical Center

Westwood, Kansas, 66205, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Utah Intermountain Medical Center

Murray, Utah, 84107, United States

RECRUITING

Novartis Investigative Site

Guangzhou, 510060, China

RECRUITING

Novartis Investigative Site

Shanghai, 200032, China

RECRUITING

Novartis Investigative Site

Tianjin, 300300, China

RECRUITING

Novartis Investigative Site

Saint-Cloud, Hauts De Seine, 92210, France

RECRUITING

Novartis Investigative Site

Bordeaux, 33076, France

RECRUITING

Novartis Investigative Site

Clermont-Ferrand, 63011, France

RECRUITING

Novartis Investigative Site

Saint-Herblain, 44805, France

RECRUITING

Novartis Investigative Site

Strasbourg, F 67085, France

RECRUITING

Novartis Investigative Site

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

Novartis Investigative Site

Erlangen, 91054, Germany

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

München, 80377, Germany

RECRUITING

Novartis Investigative Site

Gliwice, 44 101, Poland

RECRUITING

Novartis Investigative Site

Porto, 4200-072, Portugal

RECRUITING

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08035, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08036, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28034, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28040, Spain

RECRUITING

Related Publications (1)

• 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.

  PMID: 38753757 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; Fulvestrant; Goserelin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2023
• First Posted: May 23, 2023
• Study Start: November 13, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): January 26, 2032
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3); PT (1); FR (5); DE (4); ES (5); PL (1); US (6)