Phase I Study of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers

NCT06562192
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
162
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Lead sponsor
Novartis Pharmaceuticals
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Start date
2024-10-15
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Number of sites
29
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Summary
The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of \[177Lu\]Lu-NNS309 and the safety, dosimetry and imaging properties of \[68Ga\]Ga-NNS309 in patients aged ≥ 18 years with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer (BC), triple negative breast cancer (TNBC) and colorectal cancer (CRC).
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Short title
Phase I Study of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers
clinicaltrials.gov
Official title
Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-NNS309 in Patients With Pancreatic, Lung, Breast and Colorectal Cancers
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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
2031-01-16
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First posted
2024-08-20
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Registry last updated
2026-07-29
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Primary completion date
2031-01-15
clinicaltrials.gov
Start date
2024-10-15
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Participants
162
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Participant count basis
Estimated
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Planned participants
162
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Protocol amendments
6
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Number of sites
29
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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
NCT06562192
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ClinicalTrials.gov ID
NCT06562192
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Registry record
Open registry record
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Allocation
Not applicable
Model
Single group
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Number of patients with dose limiting toxicities of [177Lu]Lu-NNS309

    Timeframe: From start of study treatment until 6 weeks or 4 weeks after, depending on dosing schedule

    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]Lu-NNS309

    Timeframe: From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months

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

  3. Dose modifications for [177Lu]Lu-NNS309

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

    Dose modifications (dose interruptions and reductions) for \[177Lu\]Lu-NNS309 will be assessed and summarized using descriptive statistics. The number of patients with dose modification will be summarized by treatment groups.

  4. Dose intensity for [177Lu]Lu-NNS309

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

    Dose intensity for \[177Lu\]Lu-NNS309 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: Up to approximately 42 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: Up to approximately 42 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: Up to approximately 42 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: Up to approximately 42 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]Lu-NNS309

    Timeframe: Samples collected pre infusion to 336 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

    The \[177Lu\]Lu-NNS309 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]Lu-NNS309

    Timeframe: Samples collected pre infusion to 336 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

    The \[177Lu\]Lu-NNS309 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]Lu-NNS309

    Timeframe: Samples collected pre infusion to 336 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

    The \[177Lu\]Lu-NNS309 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]Lu-NNS309

    Timeframe: Samples collected pre infusion to 336 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

    The \[177Lu\]Lu-NNS309 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]Lu-NNS309 during the terminal phase

    Timeframe: Samples collected pre infusion to 336 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

    The \[177Lu\]Lu-NNS309 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]Lu-NNS309

    Timeframe: Samples collected pre infusion to 336 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

    The \[177Lu\]Lu-NNS309 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: Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition to 6 hr post end of infusion (EOI), 6-24hr post EOI, 24-48hr post EOI, 48-72hr post EOI. The duration of a cycle is 4 weeks or 6 weeks.

    Urine elimination data for \[177Lu\]Lu-NNS309 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]Lu-NNS309

    Timeframe: Cycle 1: Pre-infusion, beginning of infusion to first SPECT/CT image acquisition, first SPECT/CT image acquisition to 6 hr post end of infusion (EOI), 6-24hr post EOI, 24-48hr post EOI, 48-72hr post EOI. The duration of a cycle is 4 weeks or 6 weeks.

    Urine samples will be collected over specified time intervals and analyzed for radioactivity. Renal clearance of 177Lu-NNS309 will be summarized using descriptive statistics.

  13. Absorbed dose of [177Lu]Lu-NNS309

    Timeframe: Samples collected 5 hours to 336 hours post end of infusion in Cycle 1. In a subset of patients, sampling is repeated in Cycle 2 and subsequent cycles. Cycle duration is 4 or 6 weeks.

    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. Absorbed radiation dose of [68Ga]Ga-NNS309 in tumor lesions (dose expansion only)

    Timeframe: Samples collected 30 minutes to 3 hours post end of injection.

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

  15. Area Under the Curve (AUC) of [68Ga]Ga-NNS309

    Timeframe: Samples collected 5 minutes to 245 minutes post end of injection.

    The \[68Ga\]Ga-NNS309 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.

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

    Timeframe: From Imaging visit until 3 days after 68Ga-NNS309 administration, assessed up to approximately 3 days.

    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.

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

    Timeframe: From 0 up to approximately 3 hrs after [68Ga]Ga-NNS309 dosing

    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

  • Age ≥ 18 years old
  • Patients with one of the following indications:
  • Locally advanced unresectable or metastatic PDAC with disease progression following, or intolerance to cytotoxic chemotherapy, 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 targeted therapy, unless patient was ineligible to receive such therapy
  • Locally advanced unresectable or metastatic HR+/HER2- ductal or lobular BC with disease progression following, or intolerance to, at least 2 lines of therapy, unless patient was ineligible to receive such therapy
  • Locally advanced unresectable or metastatic TNBC with disease progression following, or intolerance to, at least 2 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
  • Patients must have lesions showing 68Ga-NNS309 uptake

  • Absolute neutrophil count (ANC) < 1.5 x 10^9/L, hemoglobin < 9 g/dL, or platelet count < 100 x 10^9/L
  • QT interval corrected by Fridericia's formula (QTcF) ≥ 470 msec
  • Calculated estimated glomerular filtration rate < 60 mL/min/1.73m2
  • Unmanageable urinary tract obstruction or urinary incontinence
  • Radiation therapy within 4 weeks prior to the first dose of [177Lu]Lu-NNS309

Other protocol-defined inclusion/exclusion criteria may apply.

Sources for eligibility
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  • Uni of Alabama at BirminghamBirmingham, United StatesRecruiting
  • University of California LALos Angeles, United StatesRecruiting
  • Stanford University Medical CenterPalo Alto, United StatesRecruiting
  • Mayo Clinic JacksonvilleJacksonville, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • BAMF HealthGrand Rapids, United StatesRecruiting
  • Mayo Clinic RochesterRochester, United StatesRecruiting
  • Uni Of TX MD Anderson Cancer CntrHouston, United StatesRecruiting
  • University Of WashingtonSeattle, United StatesRecruiting
  • Novartis Investigative SiteBrussels, BelgiumRecruiting
  • Novartis Investigative SiteToronto, CanadaRecruiting
  • Novartis Investigative SiteMontreal, CanadaRecruiting
  • Novartis Investigative SiteMontreal, CanadaRecruiting
  • Novartis Investigative SiteBron, FranceRecruiting
  • Novartis Investigative SiteVillejuif, FranceRecruiting
  • Novartis Investigative SiteCologne, GermanyRecruiting
  • Novartis Investigative SiteEssen, GermanyRecruiting
  • Novartis Investigative SiteMünchen, GermanyRecruiting
  • Novartis Investigative SiteRostock, GermanyRecruiting
  • Novartis Investigative SiteTel Aviv, IsraelRecruiting
  • Novartis Investigative SiteMilan, ItalyRecruiting
  • Novartis Investigative SiteReggio Emilia, ItalyRecruiting
  • Novartis Investigative SiteNijmegen, NetherlandsRecruiting
  • Novartis Investigative SiteUtrecht, NetherlandsRecruiting
  • Novartis Investigative SiteBarcelona, SpainRecruiting

And 4 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-510356-23
Sources for references
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Related records

Drugs (1)

Lead sponsors (1)

Conditions (6)