Actively Recruiting
Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer
Led by Jeeyun Lee · Updated on 2025-12-15
61
Participants Needed
1
Research Sites
113 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Despite recent advances, the prognosis of patients with advanced gastric cancer remains poor. At present, regimens that combine a platinum and fluorouracil agent either alone or in combination with a third drug such as epirubicin or taxane constitute the most effective treatment option in the first-line metastatic setting, resulting in a median OS of approximately 10 months. In the second-line setting, ramucirumab (a vascular endothelial growth factor receptor 2 antagonist) was recently approved by the United States Food and Drug Administration, and has demonstrated modest activity in patients with advanced gastric or GEJ adenocarcinoma who progressed after first-line platinum- or fluoropyrimidine-containing chemotherapy. Median OS was 5.2 months in the ramucirumab group versus 3.8 months in the placebo group. At the updated DCO of 03 June 2020 in the DS8201-A-J202 (DESTINY-Gastric01) study in HER2-positive GC or GEJ adenocarcinoma subjects assigned to T-DXd 6.4 mg/kg, T-DXd further demonstrated clinically meaningful efficacy. The median OS was 12.5 months for the T-DXd group and 8.9 months for the physician's choice group (HR = 0.60, 95% CI: 0.42, 0.86). In a prespecified subgroup analysis, the percentages of patients with an objective response were analyzed in HER2-low group. The response rate in HER2 2+ was 29% (8 of 28) with T-DXd monotherapy. Refer to the figure below for the response rate in HER2-low group in previous DESTINY trials. This is a two part, phase I/Ⅱ, open-label, single center study of afatinib in combination with T-DXd, in 2L/3L gastric cancer patients with HER2-low. The study design allows an investigation of combination dose of afatinib with T-DXd, with intensive safety monitoring to ensure the safety of the patients.
CONDITIONS
Official Title
Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients aged 19 years or older
- Histologically confirmed advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with at least one measurable lesion per modified RECIST 1.1
- HER2-low tumor status (HER2 1+ or HER2 2+ with SISH negative)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 with no deterioration before first treatment dose
- Life expectancy of at least 3 months from first dose
- Ability and willingness to comply with study treatments, visits, and examinations
- Washout period completed for prior therapies as specified (e.g., major surgery ≥4 weeks, chemotherapy ≥3 weeks)
- Adequate bone marrow, liver, and renal function within 28 days before treatment
- Female patients must use effective contraception during and for 7 months after treatment or be not of childbearing potential
- Sexually active non-sterilized males must use condoms with spermicide during and 4 months after treatment and follow contraceptive guidance
- Mandatory biopsy during screening and at disease progression
You will not qualify if you...
- History of myocardial infarction within 6 months or symptomatic congestive heart failure
- History or current interstitial lung disease or pneumonitis requiring steroids
- Pleural effusion, ascites, or pericardial effusion requiring drainage within 2 weeks before screening
- Uncontrolled infections requiring intravenous antibiotics, antivirals, or antifungals
- Active hepatitis B or C infection; only resolved or controlled cases allowed
- Untreated or symptomatic brain metastases requiring steroids or anticonvulsants
- Clinically significant corneal disease
- Prior treatment with antibody-drug conjugates containing an exatecan derivative topoisomerase I inhibitor
- Unresolved toxicities from previous cancer therapies exceeding specified criteria
- Gastrointestinal conditions preventing proper absorption of afatinib
- Active or prior autoimmune or inflammatory disorders except certain stable or controlled conditions
- Positive HIV infection or active tuberculosis
- Untreated central nervous system metastatic disease or leptomeningeal disease
- Second primary cancer except adequately treated non-melanoma skin cancer or in-situ cervical cancer with no disease for ≥3 years
- Live attenuated vaccinations within 30 days prior to study entry
- Use of medications affecting CYP enzymes with narrow therapeutic range within 2 weeks prior to afatinib
- Specific cardiac conditions including prolonged QTc, arrhythmias, uncontrolled hypertension, and heart failure
- Severe or uncontrolled systemic diseases including uncontrolled infections and severe chronic conditions
- Unresolved grade 2 or higher toxicities from previous anticancer treatments except specified exceptions
- Uncontrolled intercurrent illness or psychiatric/social conditions limiting compliance
- History of active primary immunodeficiency
- Pregnancy or breastfeeding or unwillingness to use effective contraception
- Known allergies to study drugs or excipients
- History of allogenic organ transplantation
- Significant lung diseases or prior pneumonectomy
AI-Screening
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Trial Site Locations
Total: 1 location
1
Samsung Medical Center
Seoul, South Korea
Actively Recruiting
Research Team
J
Jeeyun Lee, Ph, MD
CONTACT
J
Jeeyun Lee, Ph, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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