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Study of [177Lu]Lu-DWJ155 and [68Ga]Ga-DWJ155 in Patients With Solid Tumors

26 août 2026 mis à jour par: Novartis Pharmaceuticals

A Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-DWJ155 and Safety and Imaging Properties of [68Ga]Ga-DWJ155 in Patients With Solid Tumors

The purpose of this phase I study is to evaluate the safety, tolerability, dosimetry, and preliminary anti-tumor activity of [177Lu]Lu-DWJ155 and the safety and imaging properties of [68Ga]Ga-DWJ155 in patients with histologically or cytologically confirmed advanced HER2+, HR+/HER2-negative, or triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), HER2-3+ or 2+ (ISH positive or negative) gastric/gastroesophageal junction (GEJ) cancer, and bladder cancer.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

The study will be done in two parts. The first part is called "escalation" and the second part is called "expansion". In both parts of the study, patients will initially be imaged with a [68Ga]Ga-DWJ155 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan. In the escalation part, different doses of [177Lu]Lu-DWJ155 will then be tested to identify recommended dose(s) (RD(s)) for further evaluation. The expansion part of the study will examine the safety and preliminary efficacy of [177Lu]Lu-DWJ155 at the RD(s) determined during the escalation part.

In both parts, there will be a safety follow-up period after the last [177Lu]Lu-DWJ155 administration.

Type d'étude

Interventionnel

Inscription (Estimé)

156

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

  • Nom: Novartis Pharmaceuticals
  • Numéro de téléphone: +41613241111

Lieux d'étude

  • Australie
    • New South Wales
      • Darlinghurst, New South Wales, Australie, 2010
        • Recrutement
        • Novartis Investigative Site
  • Canada
    • Quebec
      • Montreal, Quebec, Canada, H4A 3J1
        • Recrutement
        • Novartis Investigative Site
      • Montreal, Quebec, Canada, H2X 0A9
        • Recrutement
        • Novartis Investigative Site
  • Japon
    • Chiba
      • Kashiwa, Chiba, Japon, 2778577
        • Recrutement
        • Novartis Investigative Site
  • États-Unis
    • Nebraska
      • Omaha, Nebraska, États-Unis, 68130
        • Recrutement
        • Nebraska Cancer Specialists
        • Chercheur principal:
          • Ralph Hauke
        • Contact:

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

  • Adulte
  • Adulte plus âgé

Accepte les volontaires sains

Non

La description

Inclusion Criteria:

  • Male or female patients age ≥ 18 years.
  • Patients with one of the following histologically or cytologically confirmed and documented malignancies who have progressed on or been intolerant to standard of care therapy, and are not considered appropriate for any standard therapy with proven benefit, in the investigator's judgment:

  • Dose Escalation:

    • Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
    • Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
    • Advanced NSCLC without actionable genetic alterations (AGAs) with disease progression after prior therapy in the advanced setting
    • Advanced NSCLC with AGAs who have received prior treatment
    • Measurable disease as determined by RECIST version 1.1.

  • Dose Expansion:

    • Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
    • Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
    • Advanced HR+/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
    • Advanced HR-/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
    • Advanced HR-/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
    • Advanced NSCLC with AGAs, who have received prior treatment
    • Advanced NSCLC without known AGAs who have received prior treatment.
    • Advanced gastric/GEJ cancer with HER2 IHC 3+ or 2+ (ISH + or -), following disease progression after prior therapy in the advanced setting
    • Advanced bladder cancer following disease progression after prior therapy in the advanced setting
    • Measurable disease as determined by RECIST version 1.1.

Exclusion Criteria:

  • Out-of-range laboratory values defined as:

    • Creatinine clearance < 60 mL/min (calculated using CKD-EPI 2021 formula, or measured)
    • Total bilirubin > 1.5 x ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN) or direct bilirubin > 1.5 x ULN
    • Alanine aminotransferase (ALT) > 3 x ULN, except for patients with tumor involvement of the liver who are excluded if ALT > 5 x ULN
    • Aspartate aminotransferase (AST) > 3 x ULN, except for patients with tumor involvement of the liver who are excluded if AST > 5 x ULN
    • Lipase > 1.5 x ULN
    • Absolute neutrophil count (ANC) < 1.5 x 109/L
    • Hemoglobin < 9 g/dL
    • Platelet count < 100 x 109/L
  • Initiation of hematopoietic colony stimulating factors, thrombopoietin mimetics, or erythroid stimulating agents initiated ≤ 2 weeks prior to imaging agent administration.
  • Use of transfusion support ≤4 weeks prior to imaging agent administration.
  • Impaired cardiac function or clinically significant cardiac disease.
  • Unmanageable urinary tract obstruction or urinary incontinence.
  • Any serious uncontrolled infection (acute or chronic).
  • Pregnant or breastfeeding women.

  • Treatment with any of the following anti-cancer therapies prior to imaging agent administration within the stated timeframes:

    • Prior treatment with any therapeutic radiopharmaceutical
    • < 10 half-lives for any imaging radiopharmaceutical
    • ≤ 4 weeks for external beam radiation therapy (EBRT) or brachytherapy
    • ≤ 6 months for lung-directed external beam radiotherapy
  • Patients with non-tumor uptake of [68Ga]Ga-DWJ155 in tissues or organs that, in the opinion of the investigator, increases the risk associated with [177Lu]Lu-DWJ155 treatment.

Other protocol-defined inclusion/exclusion criteria may apply.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation séquentielle
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Dose Escalation
Patients will receive [68Ga]Ga-DWJ155 and, if eligible, [177Lu]Lu-DWJ155. In this part, multiple dose levels of [177Lu]Lu-DWJ155 will be evaluated.
Test diagnostique: [68Ga]Ga-DWJ155
Radioligand imaging agent
Autres noms:
  • FKL480
Médicament: [177Lu]Lu-DWJ155
Radioligand therapy
Autres noms:
  • FML539
Expérimental: Dose Expansion
Patients will receive [68Ga]Ga-DWJ155 and, if eligible, [177Lu]Lu-DWJ155 at the recommended dose established during the dose escalation part.
Test diagnostique: [68Ga]Ga-DWJ155
Radioligand imaging agent
Autres noms:
  • FKL480
Médicament: [177Lu]Lu-DWJ155
Radioligand therapy
Autres noms:
  • FML539

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [177Lu]Lu-DWJ155
Délai: Up to approximately 53 months
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, echocardiograms (ECGs), and imaging assessments qualifying and reported as AEs.
Up to approximately 53 months
Incidence of dose-limiting toxicities (DLTs) of [177Lu]Lu-DWJ155
Délai: Up to 6 weeks
A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness/injury or concomitant medications that occurs within the first treatment cycle. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Up to 6 weeks
Frequency of dose interruptions and reductions [177Lu]Lu-DWJ155
Délai: 11 months
Number of participants with dose interruptions and/or reductions to assess the tolerability.
11 months
Dose intensity [177Lu]Lu-DWJ155
Délai: 11 months
Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure
11 months

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Overall Response Rate (ORR) per RECIST v1.1
Délai: Up to approximately 53 months
ORR is defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR) as per local review and according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
Up to approximately 53 months
Disease Control Rate (DCR) per RECIST v1.1
Délai: Up to approximately 53 months
DCR is defined as the proportion of patients with a BOR of CR, PR, or stable disease (SD) as per local review and according to RECIST v1.1.
Up to approximately 53 months
Duration of Response (DOR) per RECIST v1.1
Délai: Up to approximately 53 months
DOR is the time between the first documented response (CR or PR) and the date of progression as per local review and according to RECIST v1.1, or death due to any cause.
Up to approximately 53 months
Progression-Free Survival (PFS) per RECIST v1.1
Délai: Up to approximately 53 months
PFS is defined as the time from the date of start of treatment to the date of the first documented progression as per local review and according to RECIST v1.1 or death due to any cause.
Up to approximately 53 months
Area under the concentration-time curve (AUC) of [177Lu]Lu-DWJ155
Délai: From pre-dose up to 168 hours after the end of the infusion on Day 1
The pharmacokinetic (PK) analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. AUC will be determined by non-compartmental methods.
From pre-dose up to 168 hours after the end of the infusion on Day 1
Systemic clearance (CL) of [177Lu]Lu-DWJ155
Délai: From pre-dose up to 168 hours after the end of the infusion on Day 1
The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. CL will be determined by non-compartmental methods.
From pre-dose up to 168 hours after the end of the infusion on Day 1
Maximum observed concentration (Cmax) of [177Lu]Lu-DWJ155
Délai: From pre-dose up to 168 hours after the end of the infusion on Day 1
The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Cmax will be determined by non-compartmental methods.
From pre-dose up to 168 hours after the end of the infusion on Day 1
Volume of distribution during the terminal phase (Vz) of [177Lu]Lu-DWJ155
Délai: From pre-dose up to 168 hours after the end of the infusion on Day 1
The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Vz will be determined by non-compartmental methods.
From pre-dose up to 168 hours after the end of the infusion on Day 1
Terminal half-life (T1/2) of [177Lu]Lu-DWJ155
Délai: From pre-dose up to 168 hours after the end of the infusion on Day 1
The PK analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. T1/2 will be determined by non-compartmental methods.
From pre-dose up to 168 hours after the end of the infusion on Day 1
Urinary excretion of [177Lu]Lu-DWJ155
Délai: From pre-dose up to 72 hours after the end of the infusion on Day 1
The PK analysis will be performed based on decay-corrected urine radioactivity concentration data converted to mass units. Urinary excretion will be derived based on the percentage of injected dose excreted in urine in each collection interval and overall.
From pre-dose up to 72 hours after the end of the infusion on Day 1
Renal clearance (CLr) of [177Lu]Lu-DWJ155
Délai: From pre-dose up to 72 hours after the end of the infusion on Day 1
The PK analysis will be performed based on decay-corrected blood and urine radioactivity concentration data converted to mass units. CLr will be determined by non-compartmental methods.
From pre-dose up to 72 hours after the end of the infusion on Day 1
Absorbed radiation dose in selected organs, tumor lesions and total body of [177Lu]Lu-DWJ155
Délai: Up to 168 hours after the end of the infusion on Day 1
Single Photon Emission Computed Tomography/Computed Tomography (SPECT/CT) images will be acquired to assess total body, organ and tumor lesion dosimetry.
Up to 168 hours after the end of the infusion on Day 1
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [68Ga]Ga-DWJ155:
Délai: Up to 3 days
Incidence and severity of AEs and SAEs, including changes in laboratory values, vital signs, echocardiograms (ECGs), and cardiac imaging qualifying and reported as AEs.
Up to 3 days
Standard uptake values (SUVs) in normal tissues and selected tumor lesions of [68Ga]Ga-DWJ155
Délai: Up to approximately 1.5 hours after the end of infusion
68Ga-DWJ155 positron emission tomography/computed tomography (PET/CT) or positron emission tomography/magnetic resonance imaging (PET/MRI) imaging assessments will be performed to derive SUVs in normal tissues and selected tumor lesions.
Up to approximately 1.5 hours after the end of infusion

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Novartis Pharmaceuticals

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

16 juin 2026

Achèvement primaire (Estimé)

24 mai 2032

Achèvement de l'étude (Estimé)

24 mai 2032

Dates d'inscription aux études

Première soumission

15 juin 2026

Première soumission répondant aux critères de contrôle qualité

15 juin 2026

Première publication (Réel)

22 juin 2026

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

27 août 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

26 août 2026

Dernière vérification

1 août 2026

Plus d'information

Termes liés à cette étude

Mots clés

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • CFML539A12101
  • 2024-518348-19 (Autre identifiant: EU CTIS)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

NON

Description du régime IPD

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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