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.

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Breast Cancer

In brief

In the phase I part, to determine the recommended doses (RD) and dosing regimens of \[177Lu\]Lu-NeoB in combination with capecitabine in adult patients with gastrin releasing peptide receptor positive, estrogen receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer after progression on previous endocrine therapy in combination with a CDK4/6 inhibitor. In the phase II part, to evaluate the preliminary anti-tumor activity of two different doses/regimens of \[177Lu\]Lu-NeoB in combination with capecitabine (dose optimization).

Key facts

Study ID

NCT06247995

Run by

Novartis Pharmaceuticals

People needed

20

Starts

2024-08-14

Expected to finish

2031-09-09

Last updated by the study team

2026-07-24

Who can join

Age: 18 and older, up to 100. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Signed informed consent must be obtained prior to participation in the study.
• Participant is female or male adult ≥ 18 years old at the time of informed consent(s).
• Participant has a histologically and/or cytologically documented diagnosis of ER+ breast cancer (ER expression >10% of tumor cell nuclei stain (regardless of PgR expression) (based on the most recently analyzed tissue sample tested by a local laboratory).
• Participant has HER2-negative (as per ASCO-CAP guidelines Wolff et al 2018) breast cancer defined as a negative in situ hybridization test (ISH) or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative ISH (e.g., FISH, CISH, or SISH) (based on the most recently analyzed tissue sample tested by a local laboratory) is required.
• 5a. Participant received no more than three prior endocrine therapies (single agent or in combination with targeted therapy) regimen/s in the metastatic setting of which at least one included endocrine therapy in combination with a CDK4/6i. In addition:
• in case of confirmed presence of deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation, the participant may also have received a PARP inhibitor-based therapy.
• In case of HER2-low breast cancer (IHC 1+ or IHC 2+ with ISH negative as per ASCO-CAP guidelines Wolff et al 2023), the participant may also have received trastuzumab deruxtecan [Enhertu®]).
• Participant has metastatic breast cancer with radiologically confirmed progression of disease after the most recent therapy 7. Participant must have measurable disease, i.e., at least one measurable lesion as per RECIST 1.1. (a lesion at a previously irradiated site may only be counted as a target lesion if there is a clear sign of progression since the irradiation) as per local assessment.
• Note: If only lytic bone lesions are present, they must have at least one lesion with a soft tissue component that can be evaluated by CT or MRI and meets the definition of measurability as per RECIST 1.1 criteria (participants with only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).
• 8a. Participant has at least one target lesion [as per RECIST 1.1 and based on the baseline stand-alone contrast-enhanced CT (or MRI)] with [68Ga]Ga-NeoB uptake greater than the physiological uptake of the liver at PET/CT or PET/MRI, as per local reading. In addition:
• Participants with liver or lung disease involvement must show [68Ga]Ga-NeoB uptake greater than the physiological uptake of the liver as follows:
• If there is liver disease involvement (in the absence of lung involvement), in ≥ 50% of all CT measurable liver lesions (RECIST 1.1)
• If there is lung disease involvement (in the absence of liver involvement), in ≥ 50% of all CT measurable lung lesions (RECIST 1.1)
• Participants with both liver and lung disease involvement must show [68Ga]Ga-NeoB uptake above the liver in ≥ 50% of all CT measurable lesions either in liver or lung (RECIST 1.1) and in at least one measurable lesion in the remaining organ (lung or liver) 9a. Participants with central nervous system (CNS) involvement are eligible provided that they meet ALL the following criteria:
• At least 2 weeks from prior therapy completion (including radiation and/or surgery) to initiation of the study treatment
• Clinically stable CNS tumor at the time of screening
• Participant is not receiving steroids and/or anti-epileptic medications for brain metastases at the time of initiation of the radioligand study treatment 10. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 11a. Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by local laboratory):
• Absolute neutrophil count ≥ 1.5 × 109/L
• Platelets ≥ 100 × 109/L
• Hemoglobin ≥ 9.0 g/dL
• International Normalized Ratio (INR) ≤1.5
• Estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73m2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
• Total bilirubin (TBIL) < 1.5 × ULN (any elevated bilirubin should be asymptomatic at enrollment) except for participants with Gilbert's syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN
• In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 × ULN. If the participant has liver metastases, the participant will be eligible for the study if ALT and AST < 5 X ULN.

You may not qualify if…

• Participant with symptomatic visceral disease or any disease burden that are at risk of life-threatening complications as per the investigator's judgment.
• 2a. Participant has received >1 prior treatment with chemotherapy and/or Antibody Drug-Conjugates (ADCs) in the metastatic setting. Chemotherapy in neoadjuvant/ adjuvant setting is not considered a line of therapy, unless progression or recurrence occurred during or within 12 months after completion of adjuvant chemotherapy.
• Participant has received prior treatment with capecitabine. 4. History of hypersensitivity or contraindication to any of the study treatments or their excipients or to drugs of similar chemical classes.
• Participant has inflammatory breast cancer at screening. 6. Participant has had major surgery within 14 days prior to starting study treatment or has not recovered from major side effects.
• Participant has received any prior treatment with a therapeutic radiopharmaceutical.
• Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow.
• Participant has a concurrent malignancy or malignancy within 3 years of start of study treatment, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer.
• Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., uncontrolled ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection) based on investigator's discretion.
• Participant has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment, cause unacceptable safety risks, contraindicate participant participation in the clinical study or compromise compliance with the protocol (e.g., chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, interstitial lung disease (ILD)/ pneumonitis etc.).
• Participant has a history of or ongoing acute pancreatitis within 1 year of screening.
• History or current diagnosis of impaired cardiac function, clinically significant cardiac disease or ECG abnormalities indicating significant risk of safety for participants in the study such as:
• Documented myocardial infarction (MI), angina pectoris, cardiomyopathy, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II and third-degree AV block)
• Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• Risk factors for TdP including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
• Inability to determine the Fridericia QT correction formula (QTcF) interval
• Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening as per standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed locally
• Left Ventricular Ejection Fraction (LVEF) < 50% as determined by echocardiogram (ECHO) or MUGA.
• Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensive medication.
• Participant is currently receiving brivudine which cannot be discontinued at least 4-week prior to start of capecitabine therapy.
• 15a. Participant is currently receiving NEP inhibitors (i.e., Entresto®, racecadotril) and images for dosimetry assessments cannot be acquired for this participant as per Section 8.7.3.
• 16b. Participant with known deficiency or family history of deficiency of dihydropyrimidine dehydrogenase.
• Participant participated in a prior investigational study within 30 days prior to start of study treatment, or within 5 half-lives of the investigational product, whichever is longer; or as required by local regulations.
• Sexually active male participants unwilling to:
• remain abstinent (refrain from sexual intercourse) or

Where it is running

• UCLA Medical Center — Los Angeles, California, United States
• Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States
• Mayo Clinic - Rochester — Rochester, Minnesota, United States
• Uni Of TX MD Anderson Cancer Cntr — Houston, Texas, United States
• University Of Wisconsin — Madison, Wisconsin, United States
• Novartis Investigative Site — Darlinghurst, New South Wales, Australia
• Novartis Investigative Site — Malvern, Victoria, Australia
• Novartis Investigative Site — Toronto, Ontario, Canada
• Novartis Investigative Site — Montreal, Quebec, Canada
• Novartis Investigative Site — Tianjin, China
• Novartis Investigative Site — Grenoble, France
• Novartis Investigative Site — Saint-Herblain, France
• Novartis Investigative Site — Villejuif, France
• Novartis Investigative Site — Erlangen, Germany
• Novartis Investigative Site — Tübingen, Germany
• Novartis Investigative Site — Delft, South Holland, Netherlands
• Novartis Investigative Site — Porto, Portugal
• Novartis Investigative Site — Singapore, Singapore
• Novartis Investigative Site — Seoul, South Korea
• Novartis Investigative Site — Seoul, South Korea
• Novartis Investigative Site — L'Hospitalet de Llobregat, Barcelona, Spain
• Novartis Investigative Site — Barcelona, Spain
• Novartis Investigative Site — Madrid, Spain

Full record on ClinicalTrials.gov

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