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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer; Bladder Cancer; Non-small Cell Lung Cancer (NSCLC); Gastric/Gastroesophageal Junction (GEJ) Cancer
• Intervention / Treatment: Diagnostic test: [68Ga]Ga-DWJ155; Drug: [177Lu]Lu-DWJ155

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

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
  • 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Diagnostic test: [68Ga]Ga-DWJ155; Radioligand imaging agent; Other Names: FKL480; Drug: [177Lu]Lu-DWJ155; Radioligand therapy; Other Names: FML539
Experimental: Dose Expansion; Patients will receive [68Ga]Ga-DWJ155 and, if eligible, [177Lu]Lu-DWJ155 at the recommended dose established during the dose escalation part.	Diagnostic test: [68Ga]Ga-DWJ155; Radioligand imaging agent; Other Names: FKL480; Drug: [177Lu]Lu-DWJ155; Radioligand therapy; Other Names: FML539

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [177Lu]Lu-DWJ155	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	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	Number of participants with dose interruptions and/or reductions to assess the tolerability.	11 months
Dose intensity [177Lu]Lu-DWJ155	Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure	11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR) per RECIST v1.1	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	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	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	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	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	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	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	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	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	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	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	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:	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	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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): June 25, 2026
• Primary Completion (Estimated): May 24, 2032
• Study Completion (Estimated): May 24, 2032

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 22, 2026

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Bladder cancer; Breast cancer; Non-small cell lung cancer (NSCLC); Human Epidermal Growth Factor Receptor 2 (HER2); Radioligand therapy (RLT); [68Ga]Ga-DWJ155; FKL480; Gastric/gastroesophageal junction (GEJ); [177Lu]Lu-DWJ155; FML539
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Breast Diseases; Urologic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Urinary Bladder Diseases; Skin and Connective Tissue Diseases; Neoplasms; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Urinary Bladder Neoplasms
• Other Study ID Numbers: CFML539A12101; 2024-518348-19 (Other Identifier: EU CTIS)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No