TheranosticTrials.org

Clinical Trial · NCT06247995

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.

Overview

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).

Sponsor

Novartis

Phase

Phase 1/2

Contacts

Novartis Pharmaceuticals (CONTACT)

novartis.email@novartis.com

1-888-669-6682

Novartis Pharmaceuticals (STUDY_DIRECTOR)

Novartis Pharmaceuticals (CONTACT)

+41613241111

ClinicalTrials.gov

NCT06247995

Drug / Compound

NeoB

Isotope(s):
Target(s):
  • GRPR
Ligand Class: Peptides

NeoB

Isotope(s):
Target(s):
  • GRPR
Ligand Class: Peptides

Eligibility

Inclusion

  • 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.
  • Participant is female or male adult ≥ 18 years old at the time of informed consent(s).
  • 1. Signed informed consent must be obtained prior to participation in the study.
  • 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:

Exclusion

  • 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)
  • Documented myocardial infarction (MI), angina pectoris, cardiomyopathy, symptomatic pericarditis, or coronary artery bypass graft (CABG) within 6 months prior to study entry
  • 1\. 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.3\. 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.5\. 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.7\. Participant has received any prior treatment with a therapeutic radiopharmaceutical.8\. Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow.9\. 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.10\. 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.11\. 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.).12\. Participant has a history of or ongoing acute pancreatitis within 1 year of screening.13\. 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:
  • Risk factors for TdP including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia
  • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: