Health Trials

Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors

ConditionsClinical Stage III Gastric Cancer AJCC v8Clinical Stage III Gastroesophageal Junction Adenocarcinoma AJCC v8Clinical Stage IV Gastric Cancer AJCC v8Clinical Stage IV Gastroesophageal Junction Adenocarcinoma AJCC v8Locally Advanced Gastric CarcinomaLocally Advanced Gastroesophageal Junction AdenocarcinomaLocally Advanced Malignant Solid NeoplasmMetastatic Gastric CarcinomaMetastatic Gastroesophageal Junction AdenocarcinomaMetastatic Malignant Solid NeoplasmUnresectable Gastric CarcinomaUnresectable Gastroesophageal Junction AdenocarcinomaUnresectable Malignant Solid Neoplasm
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorNational Cancer Institute (NCI)

About this trial

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.

Eligibility criteria

Qualifiers

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

HER2 expression by IHC (1+, 2+, or 3+) or HER2 amplification by ISH or NGS (on any CLIA platform on tissue), AND

T-DXd (DS-8201a)-naive disease

Disqualifiers

As azenosertib (ZN-c3) is a substrate of CYP3A4, use of prescription or non-prescription drugs known to be moderate or strong inhibitors or inducers of CYP3A4 are prohibited with the exception of moderate or strong inhibitors or inducers of CYP3A4 that are part of the prophylactic antiemetic regimen. Chloroquine/hydroxychloroquine are metabolized by CYP3A4 and therefore, should be prohibited. For patients who have received prior moderate or strong inhibitors or inducers of CYP3A4, the required washout period is approximately 5 half-lives prior to study treatment initiation

Patients who are receiving any other investigational agents

Patients who have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study drugs

Patients who have a history of severe hypersensitivity reactions to other monoclonal antibodies (mAbs)

Trial design

Treatments tested in this trial

  • Azenosertib
  • Biopsy Procedure
  • Biospecimen Collection
  • Computed Tomography
  • Echocardiography Test
  • Magnetic Resonance Imaging
  • Multigated Acquisition Scan
  • Trastuzumab Deruxtecan

Treatment groups

48 Participants
are divided into 3 treatment groups

Sponsors and collaborators

National Cancer Institute (NCI)

Lead sponsor

Source ClinicalTrials.gov