National Cancer Institute (NCI)
This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), 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). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. 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 cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.
PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of trastuzumab deruxtecan (T-DXd; DS-8201a) in combination with azenosertib (ZN-c3) in human epidermal growth factor receptor 2 (HER2)-expressing/amplified gastric/ gastroesophageal junction (GEJ) cancer and other solid tumors. SECONDARY OBJECTIVES: I. To observe and record the antitumor activity of the T-DXd (DS-8201a) and azenosertib (ZN-c3) combination. II. To assess the pharmacodynamic effects of T-DXd (DS-8201a) in combination with azenosertib (ZN-c3). III. To assess predictors of response and acquired resistance to the T-…
Inclusion Criteria: * In the dose escalation, patients must have a histologically documented locally advanced, unresectable, or metastatic solid tumor that has progressed following at least one prior line of treatment in the metastatic setting or has no satisfactory alternative treatment option and all of the following: * HER2 expression by immunohistochemistry (IHC) (1+, 2+, or 3+) or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS) (on any Clinical Laboratory Improvements Amendments \[CLIA\] platform on tissue), AND * T-DXd (DS-8201a)-naive disease…
Given PO
Undergo biopsy
Undergo collection of blood samples
Undergo CT
Undergo ECHO
Undergo MRI
Undergo MUGA
Given IV