Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid Tumors

NCT07261631
clinicaltrials.gov
Phase
Phase 1
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Participants
180
clinicaltrials.gov
Lead sponsor
Novartis Pharmaceuticals
clinicaltrials.gov
Start date
2025-11-24
clinicaltrials.gov
Number of sites
8
clinicaltrials.gov

Summary
The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-DFC413 and safety and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with solid tumors
clinicaltrials.gov
Short title
Phase I Study of [177Lu]Lu-DFC413 in Patients With Solid Tumors
clinicaltrials.gov
Official title
A Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-DFC413 and Safety and Imaging Properties of [68Ga]Ga-NNS309 in Patients With Solid Tumors
clinicaltrials.gov

Control arm
Open label
clinicaltrials.gov
Registry reports results
No
clinicaltrials.gov
Listing at source
Listed
clinicaltrials.gov
Recruitment status
Recruiting
clinicaltrials.gov
Phase
Phase 1
clinicaltrials.gov
Study type
Interventional
clinicaltrials.gov

Completion date
2029-05-09
clinicaltrials.gov
First posted
2025-12-03
clinicaltrials.gov
Registry last updated
2026-06-17
clinicaltrials.gov
Primary completion date
2029-05-09
clinicaltrials.gov
Start date
2025-11-24
clinicaltrials.gov

Participants
180
clinicaltrials.gov
Participant count basis
Estimated
clinicaltrials.gov
Planned participants
180
clinicaltrials.gov
Protocol amendments
1
clinicaltrials.gov
Number of sites
8
clinicaltrials.gov

Data monitoring committee
Yes
clinicaltrials.gov
Registry sponsor category
Industry
clinicaltrials.gov
Lead sponsor
Novartis Pharmaceuticals
clinicaltrials.gov
Source registry
ClinicalTrials.gov
clinicaltrials.gov

Registry ID
NCT07261631
clinicaltrials.gov
ClinicalTrials.gov ID
NCT07261631
clinicaltrials.gov
Registry record
Open registry record
clinicaltrials.gov

Allocation
Not applicable
Model
Single group
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Incidence and severity of dose limiting toxicities of 177Lu-DFC413

    Timeframe: Within first treatment cycle, up to maximum 6 weeks

    A dose limiting toxicity (DLT) is defined as any adverse event or abnormal laboratory value of CTCAE (version 5.0) Grade 3 or higher that occurs within the DLT evaluation period and that is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications with a few exceptions defined in the study protocol. Other clinically significant toxicities may be considered to be DLTs, even if not Grade 3 or higher.

  2. Incidence and severity of adverse events and serious adverse events of 177Lu-DFC413

    Timeframe: From study treatment start up to approximately 42 months

    The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs) and Serious Adverse Event (TESAEs) and through the monitoring of relevant clinical and laboratory safety parameters.

  3. Dose modifications for 177Lu-DFC413

    Timeframe: From study treatment start until last dose of study treatment, assessed up to approximately 24 weeks

    Dose modifications (dose interruptions and reductions) for 177Lu-DFC413 will be assessed and summarized using descriptive statistics. The number of patients with dose modification and the reasons will be summarized by treatment groups.

  4. Dose intensity for 177Lu-DFC413

    Timeframe: From study treatment start until last dose of study treatment, assessed up to approximately 24 weeks

    Dose intensity for 177Lu-DFC413 will be assessed and summarized using descriptive statistics. Dose intensity is computed as the ratio of actual cumulative dose received and actual duration of exposure.

  1. Overall response rate (ORR)

    Timeframe: From study treatment start up to 6 months

    ORR is defined as the proportion of patients with a BOR of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guidelines.

  2. Duration of Response (DOR)

    Timeframe: From study treatment start up to 6 months

    DOR is the time between the first documented response (CR or PR) and the date of progression according to RECIST v1.1 guidelines, or death due to any cause.

  3. Disease control rate (DCR)

    Timeframe: From study treatment start up to 6 months

    DCR is defined as the proportion of patients with a BOR of CR, PR or stable disease according to RECIST v1.1 guidelines.

  4. Progression free survival (PFS)

    Timeframe: From study treatment start up to 6 months

    PFS is defined as the time from the date of start of treatment to the date of the first documented progression according to RECIST v1.1 guidelines or death due to any cause.

  5. Area Under the Curve (AUC) of 177Lu-DFC413

    Timeframe: Up to 8 days after first dose

    The 177Lu-DFC413 pharmacokinetic 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. Total body clearance of 177Lu-DFC413

    Timeframe: Up to 8 days after first dose

    The 177Lu-DFC413 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Total body clearance will be determined by non-compartmental methods.

  7. Observed maximum blood concentration (Cmax) of 177Lu-DFC413

    Timeframe: Up to 8 days after first dose

    The 177Lu-DFC413 pharmacokinetic 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. Observed maximum radioactivity concentration (Rmax) of 177Lu-DFC413

    Timeframe: Up to 8 days after first dose

    The 177Lu-DFC413 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Rmax will be determined by non-compartmental methods.

  9. Volume of distribution (Vz) of 177Lu-DFC413 during the terminal phase

    Timeframe: Up to 8 days after first dose

    The 177Lu-DFC413 pharmacokinetic analysis will be performed based on decay-corrected blood radioactivity concentration data converted to mass units. Vz will be determined by non-compartmental methods.

  10. Terminal elimination half-life (T1/2) of 177Lu-DFC413

    Timeframe: Up to 8 days after first dose

    The 177Lu-DFC413 pharmacokinetic 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.

  11. Urinary excretion of radioactivity expressed as a percentage of injected dose (%ID)

    Timeframe: Up to 3 days after first dose

    Urine elimination data for 177Lu-DFC413 will be assessed based on decay-corrected urine radioactivity concentration data. Urine elimination data will be expressed as percentage of injected dose (%ID).

  12. Renal clearance of 177Lu-DFC413

    Timeframe: Up to 3 days after first dose

    Urine samples will be collected over specified time intervals and analyzed for radioactivity. Renal clearance of 177Lu-DCF413 will be summarized using descriptive statistics.

  13. Absorbed dose of 177Lu-DFC413

    Timeframe: Up to 8 days after first dose

    Time activity curves (TACs) for the various organs and tumor lesions will be produced as fraction of injected activity per gram of tissue (%ID/g) as a function of time.

  14. Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-NNS309

    Timeframe: Up to 3 days after administration

    The distribution of adverse events will be done via the analysis of frequencies for TEAEs and TESAEs and through the monitoring of relevant clinical and laboratory safety parameters.

  15. Visual and quantitative assessment of [68Ga]Ga-NNS309 uptake in normal tissues and tumor lesions over time

    Timeframe: Up to 3 days after administration

    After \[68Ga\]Ga-NNS309 administration, \[68Ga\]Ga-NNS309 PET/CT or PET/MRI will be performed. Standardized uptake values (SUVs) of \[68Ga\]Ga-NNS309 in normal tissues and tumor lesions over time will be summarized.

Sources for outcomes
clinicaltrials.gov

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

  • Adults ≥ 18 years with one of the following indications:
  • Locally advanced unresectable or metastatic PDAC, with disease progression following, or intolerance to cytotoxic therapy, unless patient was ineligible to receive such therapy
  • Locally advanced unresectable or metastatic NSCLC without any actionable genomic alterations with disease progression following, or intolerance to chemotherapy and immunotherapy, unless patient was ineligible to receive such therapy, or locally advanced unresectable or metastatic NSCLC with an actionable genomic alteration with disease progression following, or intolerance to chemotherapy and targeted therapy, unless patient was ineligible to receive such therapy
  • Locally advanced unresectable or metastatic HR+/HER2- ductal and lobular breast cancer with disease progression following, or intolerance to, hormone therapy and CDK inhibitor, and at least one additional line of therapy, unless patient was ineligible to receive such therapy
  • Locally advanced unresectable or metastatic triple negative breast cancer (TNBC) with disease progression following, or intolerance to, at least two lines of therapy, unless patient was ineligible to receive such therapy
  • Locally advanced or metastatic unresectable CRC with disease progression following, or intolerance to cytotoxic chemotherapy, unless patient was ineligible to receive such therapy. Patients with known microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) status must also have had disease progression following, or intolerance to, immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
  • (Dose expansion only) Locally advanced unresectable or metastatic soft tissue sarcoma (excluding GIST and Kaposi) with disease progression following, or intolerance to, at least one line of systemic therapy
  • Patients must have lesions showing 68Ga-NNS309 uptake

  • Absolute neutrophil count (ANC) < 1.5 x 109/L, hemoglobin < 9 g/dL, or platelet count < 100 x 109/L
  • QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec
  • eGFR < 60 mL/min/1.73m2, calculated using CKD-EPI 2021 or measured
  • Unmanageable urinary tract obstruction or urinary incontinence
  • Presence of symptomatic CNS metastases, or CNS metastases that require local CNS-directed therapy
  • Any prior radioligand therapy
  • Radiation therapy within 4 weeks prior to the first dose of [177Lu]Lu-DFC413

Other protocol-defined inclusion/exclusion criteria may apply.

Sources for eligibility
clinicaltrials.gov

  • Novartis Investigative SiteMontreal, CanadaRecruiting
  • Novartis Investigative SiteOdense C, DenmarkRecruiting
  • Novartis Investigative SiteVandœuvre-lès-Nancy, FranceRecruiting
  • Novartis Investigative SiteEssen, GermanyRecruiting
  • Novartis Investigative SiteHaifa, IsraelRecruiting
  • Novartis Investigative SiteTel Aviv, IsraelRecruiting
  • Novartis Investigative SiteSingapore, SingaporeRecruiting
  • Novartis Investigative SiteSingapore, SingaporeRecruiting
Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-521702-18
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (8)