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NCT Number: NCT06562192

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

The purpose of this study is to evaluate the safety, tolerability, dosimetry and preliminary efficacy of [177Lu]Lu-NNS309 and the safety 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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Key information

Conditions

Pancreatic Ductal Adenocarcinoma Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Colonic Diseases Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms HR+/HER2- Ductal and Lobular Breast Cancer Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Non-small Cell Lung Cancer Rectal Diseases Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin and Connective Tissue Diseases Thoracic Neoplasms Triple Negative Breast Cancer Triple Negative Breast Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Brussels, Belgium

Loading trial locations.

About this study

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-NNS309 positron emission tomography (PET)/ computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan and will be evaluated for eligibility for [177Lu]Lu-NNS309 treatment. In the escalation part, different doses of [177Lu]Lu-NNS309 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-NNS309 at the RD(s) determined during the escalation part. The end of study will occur when all patients per disease group in the expansion part have completed the follow-up for disease progression or discontinued from the study for any reason, and all patients have completed treatment and the 36-month long-term follow-up period.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • (Dose escalation part only) 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

Exclusion criteria

  • 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
  • Creatinine clearance < 60 mL/min
  • 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.

Treatment and study plan

[68Ga]Ga-NNS309

Drug

Radioligand imaging agent

[177Lu]Lu-NNS309

Drug

Radioligand therapy

Primary outcomes

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

    Time frame: 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

    Time frame: 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

    Time frame: 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

    Time frame: 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.

Secondary outcomes

  1. Overall response rate (ORR)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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)

    Time frame: 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

    Time frame: Samples collected pre infusion to 360 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

    Time frame: Samples collected pre infusion to 360 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

    Time frame: Samples collected pre infusion to 360 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

    Time frame: Samples collected pre infusion to 360 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

    Time frame: Samples collected pre infusion to 360 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

    Time frame: Samples collected pre infusion to 360 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)

    Time frame: 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

    Time frame: 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

    Time frame: Samples collected 5 hours to 360 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. Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-NNS309

    Time frame: 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.

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

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Novartis Pharmaceuticals

CONTACT

[email protected]

1-888-669-6682

Novartis Pharmaceuticals

CONTACT

[email protected]

+41613241111

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2024
Primary completion
2031
Study completion
2031
First posted
Aug 20, 2024
Registry last updated
Jul 8, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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