Actively Recruiting
Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) Combined With Azenosertib (ZN-c3) in HER2-Expressing Gastric, Gastroesophageal Junction Cancer and Other Solid Tumors
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
48
Participants Needed
1
Research Sites
N/A
Total Duration
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AI-Summary
What this Trial Is About
Researchers are evaluating the safety, side effects, and best dose of azenosertib combined with trastuzumab deruxtecan in patients with HER2-positive gastric, gastroesophageal junction cancer, or other HER2-positive solid tumors that are locally advanced, metastatic, or unresectable. This phase I trial aims to determine how well this combination is tolerated and to observe its antitumor activity, pharmacodynamic effects, and predictors of response or resistance. Participants receive trastuzumab deruxtecan intravenously on day 1 of each 21-day cycle, combined with oral azenosertib taken on specific days within each cycle following dose escalation or dose expansion schedules. Patients are assigned to different cohorts that receive varied dosing schedules of azenosertib alongside trastuzumab deruxtecan. Assessments include echocardiography or multigated acquisition scans, biopsies, blood sample collections, and imaging with CT or MRI throughout the trial. During the study, participants undergo regular safety and response evaluations, including heart function tests and tumor imaging. After treatment ends, patients are followed up at 30 days, then every 3 months for the first 2 years, and every 6 months during the third year. The main measures are identifying the maximum tolerated dose, dose-limiting toxicities, adverse events, as well as tracking tumor response and progression over up to three years.
CONDITIONS
Brief Title
Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 years or older
- Histologically confirmed locally advanced, unresectable, or metastatic HER2-expressing/amplified gastric, gastroesophageal junction cancer, or other solid tumors
- HER2 expression by immunohistochemistry (IHC) 1+, 2+, or 3+, or HER2 amplification by in situ hybridization (ISH) or next generation sequencing (NGS)
- Disease must be trastuzumab deruxtecan (T-DXd) naive
- Received prior trastuzumab-based treatment if eligible (dose expansion only)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Karnofsky score 70% or higher)
- Adequate blood counts and organ function within 7 days before starting treatment
- Left ventricular ejection fraction (LVEF) 50% or higher by echocardiogram or MUGA within 28 days before enrollment
- Women of childbearing potential and male patients must agree to use highly effective contraception during and after the study
- Willingness to sign informed consent and undergo required biopsies (dose expansion)
You will not qualify if you...
- Use of drugs that strongly affect CYP3A4 enzyme activity within 5 half-lives before treatment
- Receiving other investigational agents
- History of severe allergic reactions to similar drugs or monoclonal antibodies
- Severe lung problems or requiring supplemental oxygen for daily living
- Pregnant or breastfeeding women
- History or current interstitial lung disease or pneumonitis
- Active infections requiring treatment at study start
- Malabsorption syndromes or inability to swallow pills
- Recent major heart problems or abnormal heart rhythms
- Prior treatment with WEE1 inhibitors or trastuzumab deruxtecan
- Uncontrolled illnesses or recent organ transplantation
- Significant gastrointestinal disorders with active diarrhea
- Spinal cord compression or other serious medical conditions that could interfere with the study
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - Up to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person) for eligibility assessments including echocardiogram or MUGA scan, biopsy, and blood sample collection
Duration - Repeated 21-day cycles until disease progression or unacceptable toxicity
Participants receive trastuzumab deruxtecan intravenously on day 1 of each 21-day cycle and azenosertib orally on specified days within each cycle. Treatment cycles continue every 21 days unless disease progression or unacceptable side effects occur. Participants undergo imaging scans and blood sample collections throughout treatment to monitor safety and antitumor activity. Some participants also undergo biopsies during the study.
Regular visits every cycle including infusion appointments and oral medication periods, imaging assessments, blood sample collections, and biopsies depending on cohort assignment
Duration - Up to 3 years
After completing study treatment, participants are followed for safety and disease status with visits at 30 days post-treatment, then every 3 months for 2 years, and every 6 months in year 3.
Visits at 30 days post-treatment, then every 3 months for 2 years, and every 6 months in year 3
Trial Site Locations
Total: 1 location
1
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
3
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