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| ID | Type | Description | Link |
|---|---|---|---|
| 2023-510356-23 | Other Identifier | CTIS |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Experimental | Patients will receive [68Ga]Ga-NNS309, and if eligible, [177Lu]Lu-NNS309 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [68Ga]Ga-NNS309 | Drug | Radioligand imaging agent |
| |
| [177Lu]Lu-NNS309 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients with dose limiting toxicities of [177Lu]Lu-NNS309 | 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. | From start of study treatment until 6 weeks or 4 weeks after, depending on dosing schedule |
| Incidence and severity of adverse events and serious adverse events of [177Lu]Lu-NNS309 | 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. | From start of study treatment until completion of the 36 month follow up, assessed up to approximately 42 months |
| Dose modifications for [177Lu]Lu-NNS309 | 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. | From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks |
| Dose intensity for [177Lu]Lu-NNS309 | 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. | From start of study treatment until last dose of study treatment, assessed up to approximately 24 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Overall response rate (ORR) | 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. | Up to approximately 42 months |
| Duration of Response (DOR) |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Novartis Pharmaceuticals | Contact | 1-888-669-6682 | novartis.email@novartis.com | |
| Novartis Pharmaceuticals | Contact | +41613241111 | novartis.email@novartis.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Uni of Alabama at Birmingham | Recruiting | Birmingham | Alabama | 35249 | United States |
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| Drug |
Radioligand therapy |
|
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. |
| Up to approximately 42 months |
| Disease control rate (DCR) | DCR is defined as the proportion of patients with a BOR of CR, PR or stable disease according to RECIST v1.1 guidelines. | Up to approximately 42 months |
| Progression free survival (PFS) | 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. | Up to approximately 42 months |
| Area Under the Curve (AUC) of [177Lu]Lu-NNS309 | 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. | 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. |
| Total body clearance of [177Lu]Lu-NNS309 | 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. | 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. |
| Observed maximum blood concentration (Cmax) of [177Lu]Lu-NNS309 | 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. | 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. |
| Observed maximum radioactivity concentration (Rmax) of [177Lu]Lu-NNS309 | 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. | 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. |
| Volume of distribution (Vz) of [177Lu]Lu-NNS309 during the terminal phase | 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. | 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. |
| Terminal elimination half-life (T1/2) of [177Lu]Lu-NNS309 | 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. | 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. |
| Urinary excretion of radioactivity expressed as a percentage of injected dose (%ID) | 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). | 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. |
| Renal clearance of [177Lu]Lu-NNS309 | Urine samples will be collected over specified time intervals and analyzed for radioactivity. Renal clearance of 177Lu-NNS309 will be summarized using descriptive statistics. | 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. |
| Absorbed dose of [177Lu]Lu-NNS309 | 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. | 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. |
| Incidence and severity of adverse events and serious adverse events of [68Ga]Ga-NNS309 | 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. | From Imaging visit until 3 days after 68Ga-NNS309 administration, assessed up to approximately 3 days. |
| Visual and quantitative assessment of [68Ga]Ga-NNS309 uptake in normal tissues and tumor lesions over time | 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. | From 0 up to approximately 3 hrs after [68Ga]Ga-NNS309 dosing |
| University of California LA | Recruiting | Los Angeles | California | 90095 | United States |
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| Stanford University Medical Center | Recruiting | Palo Alto | California | 94304 | United States |
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| Mayo Clinic Jacksonville | Recruiting | Jacksonville | Florida | 32224 | United States |
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| Massachusetts General Hospital | Recruiting | Boston | Massachusetts | 02114 | United States |
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| BAMF Health | Recruiting | Grand Rapids | Michigan | 49503 | United States |
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| Mayo Clinic Rochester | Recruiting | Rochester | Minnesota | 55905 | United States |
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| Uni Of TX MD Anderson Cancer Cntr | Recruiting | Houston | Texas | 77030 | United States |
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| University Of Washington | Recruiting | Seattle | Washington | 98109 | United States |
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| Novartis Investigative Site | Recruiting | Brussels | 1000 | Belgium |
| Novartis Investigative Site | Recruiting | Toronto | Ontario | M5G 2M9 | Canada |
| Novartis Investigative Site | Recruiting | Montreal | Quebec | H2X 1R9 | Canada |
| Novartis Investigative Site | Recruiting | Montreal | Quebec | H3T 1E2 | Canada |
| Novartis Investigative Site | Recruiting | Bron | 69677 | France |
| Novartis Investigative Site | Recruiting | Villejuif | 94800 | France |
| Novartis Investigative Site | Recruiting | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Novartis Investigative Site | Recruiting | Essen | 45147 | Germany |
| Novartis Investigative Site | Recruiting | München | 80377 | Germany |
| Novartis Investigative Site | Recruiting | Rostock | 18057 | Germany |
| Novartis Investigative Site | Recruiting | Tel Aviv | 6423906 | Israel |
| Novartis Investigative Site | Recruiting | Milan | MI | 20133 | Italy |
| Novartis Investigative Site | Recruiting | Reggio Emilia | RE | 42123 | Italy |
| Novartis Investigative Site | Recruiting | Nijmegen | Gelderland | 6500HB | Netherlands |
| Novartis Investigative Site | Recruiting | Utrecht | 3584 CX | Netherlands |
| Novartis Investigative Site | Recruiting | Barcelona | 08036 | Spain |
| Novartis Investigative Site | Recruiting | Madrid | 28009 | Spain |
| Novartis Investigative Site | Recruiting | Madrid | 28040 | Spain |
| Novartis Investigative Site | Recruiting | Geneva | 1211 | Switzerland |
| Novartis Investigative Site | Recruiting | Lausanne | 1011 | Switzerland |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| D064726 | Triple Negative Breast Neoplasms |
| D015179 | Colorectal Neoplasms |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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