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

Descrizione riassuntiva dello studio

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)

Intervento studiato

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)

Malattie studiate

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)

Sponsor

Novartis Pharma Schweiz AG Suurstoffi 14 6343 Rotkreuz

(BASEC)

Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)

Commissione d'etica Ginevra

(BASEC)

Data di approvazione del comitato etico

11.02.2025

(BASEC)

Risultati dello studio