OncoMatch/Clinical Trials/NCT06085755
Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer
Is NCT06085755 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including Trastuzumab deruxtecan and Afatinib for stomach neoplasm.
Treatment: Trastuzumab deruxtecan · Afatinib — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Gastric Cancer
Biomarker criteria
Required: HER2 (ERBB2) low expression (HER2 1+, HER2 2+ (SISH negative)) (HER2 1+ or HER2 2+ (SISH negative))
HER2-low (HER2 1+, HER2 2+ (SISH negative))
Disease stage
Metastatic disease required
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Cannot have received: antibody-drug conjugate (exatecan derivative, topoisomerase I inhibitor)
Prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor
Lab requirements
Blood counts
Hemoglobin ≥8.0 g/dL (no transfusion within 1 week prior); ANC ≥ 1.5 x 10^9/L (no G-CSF within 2 weeks prior); Platelet count ≥100 x 10^9/L (no transfusion within 1 week prior); International normalised ratio or Prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤ 1.5 × ULN
Kidney function
Serum creatinine ≤1.5 x institutional ULN; CrCl ≥30 mL/min as determined by Cockcroft Gault (using actual body weight)
Liver function
Total bilirubin ≤ 1.5 x institutional ULN or < 3×ULN in the presence of documented Gilbert's syndrome or liver metastases at baseline; AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional ULN unless liver metastases are present in which case it must be ≤ 5x ULN; Serum albumin ≥ 2.5 g/dL
Cardiac function
Mean QTc < 470 ms; no clinically important ECG abnormalities; LVEF ≥ 55%; no symptomatic heart failure (NYHA II-IV); no recent MI, unstable angina, arrhythmia, or severe valvular disease
Patients must have acceptable bone marrow, liver and renal function measured within 28 days prior to administration of study treatment as defined below: ... See also cardiac exclusion criteria.
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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