Phase I, open-label, multicenter study to evaluate the safety, tolerability, dosimetry, and preliminary activity of [177Lu]Lu-NNS309 in patients with pancreatic, lung, breast, and colorectal cancers
Summary description of the study
NNS309 is a peptide that binds to the fibroblast activation protein (FAP) with high affinity via a FAP-binding motif and includes a metal chelator of dodecanetetraacetic acid (DOTA) for radiolabeling with either gallium-68 (68Ga) for PET imaging or lutetium-177 (177Lu) for treatment. The objective of this Phase I study is to evaluate the safety, tolerability, dosimetry, and preliminary antitumor activity of 177Lu-NNS309 in patients with advanced solid tumors expressing FAP with a high unmet need, particularly locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer, triple-negative breast cancer (TNBC), and colorectal cancer (CRC). The study will also serve as a platform to perform an initial assessment of 68Ga-NNS309 as an imaging agent, with the ultimate goal of co-developing both as a theranostic pair (i.e., therapeutic and diagnostic). Data and samples will be collected as described to support the study objectives and may also be used to learn more about the study indication(s) and/or treatments.
(BASEC)
Intervention under investigation
The study includes a dose escalation phase, followed by a dose extension phase. Once the dose(s) (DR) and the recommended regimen(s) of 177Lu-NNS309 as monotherapy are determined, the extension phase can begin. In the escalation and extension phases, patients will be selected and then examined by PET/CT with 68Ga-NNS309 or PET/MRI with 68Ga-NNS309 to assess eligibility for treatment with 177Lu-NNS309. A patient will receive treatment with 177Lu-NNS309 if all measurable lesions show uptake of 68Ga-NNS309 and if they meet all other eligibility criteria. Confirmation of eligibility will trigger the initiation of the centralized manufacturing of 177Lu-NNS309 and the shipment of the dose to the center. 68Ga-NNS309 and 177Lu-NNS309 are considered experimental medicinal products (EMPs) in this protocol. Participating institutions may require patients to stay overnight at the hospital or another facility during days when the assessment schedule is intensive (e.g., imaging and blood sampling for 177Lu-NNS309 dosimetry assessments). This decision is based on local regulations, medical judgment, and patient preference. Prolongation of hospitalization may be considered based on the overall condition of the patients assessed by the study physician.
(BASEC)
Disease under investigation
Locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), HR+/HER2- ductal and lobular breast cancer, triple-negative breast cancer (TNBC), and colorectal cancer (CRC).
(BASEC)
• Locally advanced, unresectable, or metastatic non-squamous PDAC with disease progression after at least 1 line of treatment, or intolerance to it • Locally advanced, unresectable, or metastatic non-squamous NSCLC with disease progression after at least 1 line of treatment or intolerance to it • Locally advanced unresectable or metastatic HR+/HER2- ductal or lobular breast cancer with disease progression after at least 1 line of treatment or intolerance to it (BASEC)
Exclusion criteria
• Patients with non-tumoral uptake of 68Ga-NNS309 in tissues or organs that, in the opinion of the study physicians, increases the risk associated with treatment with 177Lu-NNS309, will not be eligible for treatment with 177Lu-NNS309. This may include, but is not limited to, fibrotic processes involving the liver, kidneys, or lungs. • Absolute neutrophil count (ANC) < 1.5 x 10^9/l, hemoglobin < 10 g/dl, or platelet count < 100 x 10^9/l • Creatinine clearance < 60 ml/min (BASEC)
Trial sites
Geneva
(BASEC)
Sponsor
Novartis Pharma Schweiz AG Suurstoffi 14 6343 Rotkreuz
(BASEC)
Contact
Contact Person Switzerland
Mathilde Ritter
+41797926732
mathilde.ritter@clutternovartis.comNovartis Pharma Schweiz AG Suurstoffi 14 6343 Rotkreuz
(BASEC)
Scientific Information
not available
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Geneva
(BASEC)
Date of authorisation
11.02.2025
(BASEC)
ICTRP Trial ID
not available
Official title (approved by ethics committee)
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 (BASEC)
Academic title
not available
Public title
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Disease under investigation
not available
Intervention under investigation
not available
Type of trial
not available
Trial design
not available
Inclusion/Exclusion criteria
not available
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Primary and secondary end points
not available
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Registration date
not available
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
not available
Secondary trial IDs
not available
Results-Individual Participant Data (IPD)
not available
Further information on the trial
not available
Results of the trial
Results summary
not available
Link to the results in the primary register
not available