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.

NCT06247995 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: CAAA603D121012023-506717-21
• Study Type: interventional
• Target: 58
• Locations: 13 countries
• Sites: 32

Brief Summary

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).

Conditions

Breast Cancer

Keywords

metastatic; Estrogen receptor; ER positive; HER2 negative; radioligant therapy; Theranostic; GRPR; neoB

Outcome Measures

Primary Outcomes (9)

• Phase I: Incidence and severity of dose limiting toxicities (DLTs)

  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 and capecitabine. The National Cancer Institute (NCI) CTCAE version 5.0 will be used for all grading.

  42 days after the first administration of [177Lu]Lu-NeoB

• Phase I: Incidence and severity of adverse events and serious adverse events for 177-Lu-NeoB in combination with capecitabine

  The distribution of adverse events for 177-Lu-NeoB in combination with capecitabine will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters.

  From start of study treatment until 56 days after the last dose of study treatment, assessed up to approximately 33 months

• Phase I: Dose modifications for [177Lu]Lu-NeoB in combination with capecitabine

  Dose modifications (dose interruptions, dose discontinuations and reductions) for \[177Lu\]Lu-NeoB in combination with capecitabine will be assessed and summarized using descriptive statistics.

  From start of study treatment until the last dose of study treatment, assessed up to approximately 31 months

• Phase II: Objective Response Rate (ORR)

  Objective Response Rate (ORR) with confirmed response 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.

  From date of randomization until date of progression, death or further antineoplastic therapy, whichever comes first, assessed up to approximately 88 months

• Phase II: Clinical Benefit Rate (CBR)

  Clinical Benefit Rate (CBR) with confirmed response 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.

  From date of randomization until date of progression, death or further antineoplastic therapy, whichever comes first, assessed up to approximately 88 months

• Phase II: Time to Response (TTR)

  Time to response is the time from the date of randomization to the first documented response (Complete Response (CR) or Partial Response (PR), which must be confirmed subsequently) as per local review and according to RECIST 1.1.

  From date of randomization until first documented evidence of CR or PR (the response prior to confirmation), assessed up to approximately 88 months

• Phase II: Duration of Response (DoR)

  Duration of Overall Response (DoR) applies only to participants whose best overall response is confirmed CR or confirmed PR according to RECIST 1.1. The start date is the date of first documented confirmed response (CR or PR) and the end date is the date defined as first documented progression or death due to underlying cancer.

  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 88 months

• Phase II: 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.

  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 88 months

• Phase II: 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.

  From the date of first dose until date of death from any cause, assessed up to approximately 88 months

Secondary Outcomes (19)

• Phase I and II: Time activity curves (TACs) related to [177Lu]Lu-NeoB

  After First, Third and Fifth [177Lu]Lu-NeoB administrations: 1-4hrs, 24hrs, 48hrs and 168hrs after infusion.

• Phase I and II: Absorbed radiation doses of [177Lu]Lu-NeoB in organs and target lesions

  After First, Third and Fifth [177Lu]Lu-NeoB administrations: 1-4hrs, 24hrs, 48hrs and 168hrs after infusion.

• Phase I and II: Concentration of [177Lu]Lu-NeoB in blood over time

  First [177Lu]Lu-NeoB administration: 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)

• Phase I and II: Maximum plasma concentration (Cmax) of [177Lu]Lu-NeoB in blood over time

  First [177Lu]Lu-NeoB administration: 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)

• Phase I and II: Time of observed drug concentration occurrence (Tmax) of [177Lu]Lu-NeoB in blood over time

  First [177Lu]Lu-NeoB administration: 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 (4)

Dose A: [177Lu]Lu-NeoB 150mCi q6w + capecitabine

EXPERIMENTAL

\[177Lu\]Lu-NeoB 150mCi q6w + Capecitabine 1000mg/ m2 BID Day1-14 in a 21-day schedule

Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-NeoB; Drug: Capecitabine

Dose B: [177Lu]Lu-NeoB 100mCi q3w + capecitabine

EXPERIMENTAL

\[177Lu\]Lu-NeoB 100mCi q3w+ Capecitabine 1000mg/m2 BID Day1-14 in a 21-day schedule

Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-NeoB; Drug: Capecitabine

Dose C: [177Lu]Lu-NeoB 200mCi q6w + capecitabine

EXPERIMENTAL

\[177Lu\]Lu-NeoB 200mCi q6w + Capecitabine 1000mg/m2 BID Day1-14 in a 21-day schedule

Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-NeoB; Drug: Capecitabine

Dose D: [177Lu]Lu-NeoB 100mCi q6w + capecitabine

EXPERIMENTAL

\[177Lu\]Lu-NeoB 100mCi q6w + Capecitabine 1000mg/m2 BID Day1-14 in a 21-day schedule

Drug: [68Ga]Ga-NeoB; Drug: [177Lu]Lu-NeoB; Drug: Capecitabine

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.

Also known as: gallium NeoB

Dose A: [177Lu]Lu-NeoB 150mCi q6w + capecitabine; Dose B: [177Lu]Lu-NeoB 100mCi q3w + capecitabine; Dose C: [177Lu]Lu-NeoB 200mCi q6w + capecitabine; Dose D: [177Lu]Lu-NeoB 100mCi q6w + capecitabine

[177Lu]Lu-NeoB DRUG

\[177Lu\]Lu-NeoB is a radioligand therapy drug.

Also known as: lutetium neoB

Dose A: [177Lu]Lu-NeoB 150mCi q6w + capecitabine; Dose B: [177Lu]Lu-NeoB 100mCi q3w + capecitabine; Dose C: [177Lu]Lu-NeoB 200mCi q6w + capecitabine; Dose D: [177Lu]Lu-NeoB 100mCi q6w + capecitabine

Capecitabine DRUG

Capecitabine is a chemotherapy drug.

Dose A: [177Lu]Lu-NeoB 150mCi q6w + capecitabine; Dose B: [177Lu]Lu-NeoB 100mCi q3w + capecitabine; Dose C: [177Lu]Lu-NeoB 200mCi q6w + capecitabine; Dose D: [177Lu]Lu-NeoB 100mCi q6w + capecitabine

Eligibility Criteria

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

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.
• a. 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).
• a. 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

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.
• a. 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (32)

UCLA Medical Center

Los Angeles, California, 90095, United States

RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Uni Of TX MD Anderson Cancer Cntr

Houston, Texas, 77030, United States

RECRUITING

University Of Wisconsin

Madison, Wisconsin, 53792, United States

RECRUITING

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Novartis Investigative Site

Malvern, Victoria, 3144, Australia

RECRUITING

Novartis Investigative Site

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Novartis Investigative Site

Guangzhou, 510060, China

RECRUITING

Novartis Investigative Site

Tianjin, 300308, China

RECRUITING

Novartis Investigative Site

Bordeaux, 33076, France

RECRUITING

Novartis Investigative Site

Grenoble, 38043, France

RECRUITING

Novartis Investigative Site

Saint-Herblain, 44805, France

RECRUITING

Novartis Investigative Site

Strasbourg, 67200, France

RECRUITING

Novartis Investigative Site

Villejuif, 94800, France

RECRUITING

Novartis Investigative Site

Erlangen, 91054, Germany

RECRUITING

Novartis Investigative Site

Essen, 45147, Germany

RECRUITING

Novartis Investigative Site

Tübingen, 72076, Germany

RECRUITING

Novartis Investigative Site

Meldola, FC, 47014, Italy

RECRUITING

Novartis Investigative Site

Reggio Emilia, RE, 42123, Italy

RECRUITING

Novartis Investigative Site

Delft, South Holland, 2625 AD, Netherlands

RECRUITING

Novartis Investigative Site

Porto, 4200-072, Portugal

RECRUITING

Novartis Investigative Site

Singapore, 168583, Singapore

RECRUITING

Novartis Investigative Site

Seoul, 03080, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 05505, South Korea

RECRUITING

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

RECRUITING

Novartis Investigative Site

Barcelona, 08036, Spain

RECRUITING

Novartis Investigative Site

Madrid, 28041, Spain

RECRUITING

Novartis Investigative Site

Seville, 41013, Spain

RECRUITING

Novartis Investigative Site

London, W12 0HS, United Kingdom

RECRUITING

Novartis Investigative Site

Sheffield, S10 2SJ, United Kingdom

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Interventions

Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

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

Study Design

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

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: February 8, 2024
• Study Start: August 14, 2024
• Primary Completion (Estimated): September 9, 2031
• Study Completion (Estimated): September 9, 2031
• Last Updated: November 6, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (5); CA (2); PT (1); AU (2); IT (2); GB (2); FR (5); DE (3); SG (1); KR (2); ES (4); CN (2); NL (1)