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

NCT07660055
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
156
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Lead sponsor
Novartis Pharmaceuticals
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Start date
2026-06-16
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Number of sites
5
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Summary
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.
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Short title
Study of [177Lu]Lu-DWJ155 and [68Ga]Ga-DWJ155 in Patients With Solid Tumors
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Official title
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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2032-05-24
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First posted
2026-06-22
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Registry last updated
2026-08-27
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Primary completion date
2032-05-24
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Start date
2026-06-16
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Participants
156
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Participant count basis
Estimated
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Planned participants
156
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Protocol amendments
1
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Number of sites
5
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Novartis Pharmaceuticals
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07660055
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ClinicalTrials.gov ID
NCT07660055
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  2. Incidence of dose-limiting toxicities (DLTs) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  3. Frequency of dose interruptions and reductions [177Lu]Lu-DWJ155

    Timeframe: 11 months

    Number of participants with dose interruptions and/or reductions to assess the tolerability.

  4. Dose intensity [177Lu]Lu-DWJ155

    Timeframe: 11 months

    Dose intensity defined as the ratio of actual cumulative dose received and actual duration of exposure

  1. Overall Response Rate (ORR) per RECIST v1.1

    Timeframe: 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).

  2. Disease Control Rate (DCR) per RECIST v1.1

    Timeframe: 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.

  3. Duration of Response (DOR) per RECIST v1.1

    Timeframe: 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.

  4. Progression-Free Survival (PFS) per RECIST v1.1

    Timeframe: 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.

  5. Area under the concentration-time curve (AUC) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  6. Systemic clearance (CL) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  7. Maximum observed concentration (Cmax) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  8. Volume of distribution during the terminal phase (Vz) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  9. Terminal half-life (T1/2) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  10. Urinary excretion of [177Lu]Lu-DWJ155

    Timeframe: 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.

  11. Renal clearance (CLr) of [177Lu]Lu-DWJ155

    Timeframe: 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.

  12. Absorbed radiation dose in selected organs, tumor lesions and total body of [177Lu]Lu-DWJ155

    Timeframe: 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.

  13. Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) of [68Ga]Ga-DWJ155:

    Timeframe: 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.

  14. Standard uptake values (SUVs) in normal tissues and selected tumor lesions of [68Ga]Ga-DWJ155

    Timeframe: 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.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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.

  • 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.

Sources for eligibility
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  • Nebraska Cancer SpecialistsOmaha, United StatesRecruiting
  • Novartis Investigative SiteDarlinghurst, AustraliaRecruiting
  • Novartis Investigative SiteMontreal, CanadaRecruiting
  • Novartis Investigative SiteMontreal, CanadaRecruiting
  • Novartis Investigative SiteKashiwa, JapanRecruiting
Sources for sites
clinicaltrials.gov

Other registry identifiers

  • 2024-518348-19
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (5)