Phase I Trial of DS-8201a (Trastuzumab Deruxtecan) in Combination With Neratinib in Solid Tumors With HER2 Alterations

This phase I trial tests the safety, side effects, and best dose of neratinib in combination with trastuzumab deruxtecan in treating patients with solid tumors that have spread from where it first started (primary site) to other places in the body (metastatic) or that cannot be removed by surgery (unresectable), and have changes in a gene called human epidermal growth factor receptor 2 (HER2). Neratinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals tumor cells to multiply. This helps slow or stop the spread of tumor cells. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Adding neratinib to trastuzumab deruxtecan may be able to shrink cancer with a change in the HER2 gene.

Procedure: Biopsy Procedure, Procedure: Biospecimen Collection, Procedure: Computed Tomography, Procedure: Echocardiography Test, Procedure: Multigated Acquisition Scan, Drug: Neratinib Maleate, Biological: Trastuzumab Deruxtecan