A first-in-human phase I trial with antibody drug conjugate ADCT-701 in neuroendocrine tumours and carcinomas

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Introduction: Neuroendocrine neoplasms (NENs) consist of neuroendocrine tumours and neuroendocrine carcinomas, which are rare malignancies found in various anatomical sites, including the gastrointestinal tract, pancreatic islets, lungs, and adrenal glands. Poorly differentiated NECs are classified as high-grade carcinomas that bear resemblance to small-cell lung cancer; however, these patients experience a high risk of relapse and demonstrate a limited response to additional systemic therapies. Adrenocortical carcinoma (ACC) is another rare cancer and currently, no targeted therapies have demonstrated significant effectiveness for this condition. Preclinical investigations have indicated that Delta-like non-canonical notch ligand 1 (DLK1) is expressed in various neuroendocrine neoplasms, including ACC, SCLC, neuroblastoma, pheochromocytoma, and paraganglioma.

Aim(s): ADCT-701, a humanised antibody targeting DLK1, has shown potential in suppressing tumour growth and enhancing survival across multiple cancer models expressing this marker with the primary endpoint to determine the maximum tolerated dose (MTD).

Materials and methods: This Phase I dose escalation study aims to enrol patients with histologically confirmed neuroendocrine neoplasms or malignant ACC with evaluable disease. A 3+3 design will be utilised to assess up to ten different dose levels. Dose escalation will continue unless dose-limiting toxicities occur, the maximum tolerated dose is reached, or an optimal dose is established. The primary endpoint of the study is to ascertain the MTD in patients with NENs or ACC.

Conference:

Presenting Author: Del Rivero J

Authors: Del Rivero J, Glod J, Magee T, Cooper K, Rivero A,

Keywords: NEN, NEC, NET, ACC, ADC, ADCT-701,