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Trials / Recruiting

RecruitingNCT06364410

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

Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing/Amplified Gastric/Gastroesophageal Junction Cancer and Other Solid Tumors

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
48 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

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.

Detailed description

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-DXd (DS-8201a) and azenosertib (ZN-c3) combination. OUTLINE: This is a dose-escalation study of azenosertib followed by a dose-expansion study. DOSE ESCALATION: Patients receive T-DXd intravenously (IV) over 30-90 minutes on day 1 of each cycle and azenosertib orally (PO) once daily (QD) on days 1-5, 8-12, and 15-19 or on days 2-5, 9-12 and 16-19 or on days 2-5 and 9-12 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and collection of blood samples at screening and on study and undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. DOSE EXPANSION: Patients are assigned to 1 of 2 cohorts. COHORT 1: Patients receive T-DXd IV over 30-90 minutes on day 1 of each cycle and azenosertib PO QD on days 8-12 and 15-19 or days 9-12 and 16-19 or days 9-12 of cycle 1 and days 1-5, 8-12, and 15-19 in subsequent cycles. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial. Patients also undergo biopsy at screening and on study. COHORT 2: Patients receive T-DXd IV over 30-90 minutes on day 1 of each cycle and azenosertib PO QD on days 1-5, 8-12, and 15-19 of each cycle. Patients also undergo ECHO or MUGA and collection of blood samples at screening and on study and undergo CT or MRI throughout the trial. Patients also undergo biopsy at screening and on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months in years 1 and 2 and every 6 months in year 3.

Conditions

Interventions

TypeNameDescription
DRUGAzenosertibGiven PO
PROCEDUREBiopsy ProcedureUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo collection of blood samples
PROCEDUREComputed TomographyUndergo CT
PROCEDUREEchocardiography TestUndergo ECHO
PROCEDUREMagnetic Resonance ImagingUndergo MRI
PROCEDUREMultigated Acquisition ScanUndergo MUGA
BIOLOGICALTrastuzumab DeruxtecanGiven IV

Timeline

Start date
2025-02-03
Primary completion
2027-07-08
Completion
2027-07-08
First posted
2024-04-15
Last updated
2026-04-13

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT06364410. Inclusion in this directory is not an endorsement.