Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer (NCT06085755) | Clinical Trial Compass
RecruitingPhase 1/2
Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer
South Korea61 participantsStarted 2024-09-30
Plain-language summary
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/â…¡, 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.
Who can participate
Age range19 Years
SexALL
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Inclusion criteria
✓. Provision of fully informed consent prior to any study specific procedures.
✓. Patients must be ≥ 19 years of age
✓. Has a pathologically documented advanced or metastatic adenocarcinoma of gastric or gastroesophageal junction with at least one measurable lesion according to the modified RECIST 1.1 are eligible
✓. HER2-low (HER2 1+, HER2 2+ (SISH negative))
✓. Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.
✓. ECOG performance status 0-1 with no deterioration between screening and the first dose of study treatment.
✓. Patients must have a life expectancy ≥ 3 months from proposed first dose date.
✓. Patients must have had a washout period of 2 weeks for any prior therapy prior to the start of study drug. The following intervals between the end of the prior treatment and first dose of study drug must be observed:
Exclusion criteria
What they're measuring
1
Adverse events by NCI-CTCAE v5.0
Timeframe: through study completion, an average of 30 months
2
ORR (Objective response rate)
Timeframe: through study completion, an average of 30 months
✕. Medical history of myocardial infarction within 6 months before registration, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV, Section 17.4), troponin levels consistent with myocardial infarction as defined according to American College of Cardiology (ACC) guidelines, unstable angina, or serious cardiac arrhythmia requiring treatment.
✕. History of (non-infectious) ILD / pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
✕. Has a pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). (Drainage and CART are not allowed within 2 weeks prior to screening assessment)
✕. Has uncontrolled infection requiring IV injection of antibiotics, antivirals, or antifungals.
✕. Active hepatitis B or C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1. Subjects with past or resolved hepatitis B virus (HBV) infection who are anti-HBc positive (+) are eligible only if they are HBsAg negative (-). Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
✕. Has clinically active brain metastases, defined as untreated and symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Subjects with treated brain metastases that are no longer symptomatic and who do not require treatment with steroids for at least three weeks may be included in the study if they have recovered from the acute toxic effect of radiotherapy. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy and study enrollment/randomization.
✕. Has clinically significant corneal disease in the opinion of the investigator.
✕. Prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.