National Cancer Institute (NCI)
This phase I/II trial tests the safety, side effects, best dose and how well giving selumetinib with trastuzumab deruxtecan (DS-8201a) works for the treatment of pancreatic ductal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. DS-8201a 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 selumetinib with DS-8201a may be safe, tolerable and/or effective in treating patients with advanced, unresectable or metastatic pancreatic ductal adenocarcinoma.
PRIMARY OBJECTIVES: I. To assess dose limiting toxicities (DLTs) and determine the recommended phase 2 dose (RP2D) of the combination of selumetinib (AZD6244 hydrogen sulfate) and DS-8201a (trastuzumab deruxtecan) in patients with pancreatic ductal adenocarcinoma (PDAC). (Escalation phase) II. To assess the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. (Phase II \[expansion phase\]) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the safety and tolerability of the combination of selumetinib (AZD624…
Inclusion Criteria: * Review of eligibility criteria by the study principal investigator (PI) is required prior to enrollment * Patients must have histologically or cytologically confirmed adenocarcinoma of the pancreas * Patients must have unresectable or metastatic disease with KRAS mutation per Next Generation Sequencing (NGS) tumor testing and HER2 immunohistochemistry (IHC) positivity (2+ or above for dose escalation and per decision rule for phase II), as determined by a Clinical Laboratory Improvement Act (CLIA)-certified kit using gastric cancer criteria * Patients must have measurabl…
Undergo blood sample collection
Undergo diagnostic imaging
Undergo echocardiography
Undergo MUGA scan
Given PO
Given IV