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
Résumé de l'étude
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 étudiée
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)
Maladie en cours d'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)
Critères d'exclusion
• 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)
Lieu de l’étude
Genève
(BASEC)
Sponsor
Novartis Pharma Schweiz AG Suurstoffi 14 6343 Rotkreuz
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Mathilde Ritter
+41797926732
mathilde.ritter@clutternovartis.comNovartis Pharma Schweiz AG Suurstoffi 14 6343 Rotkreuz
(BASEC)
Informations scientifiques
non disponible
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale d'éthique de Genève
(BASEC)
Date d'approbation du comité d'éthique
11.02.2025
(BASEC)
Identifiant de l'essai ICTRP
non disponible
Titre officiel (approuvé par le comité d'éthique)
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)
Titre académique
non disponible
Titre public
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Maladie en cours d'investigation
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Intervention étudiée
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Type d'essai
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Plan de l'étude
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Critères d'inclusion/exclusion
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Critères d'évaluation principaux et secondaires
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Date d'enregistrement
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Inclusion du premier participant
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Sponsors secondaires
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Contacts supplémentaires
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ID secondaires
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Résultats-Données individuelles des participants
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Informations complémentaires sur l'essai
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Résultats de l'essai
Résumé des résultats
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Lien vers les résultats dans le registre primaire
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