Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer

Sponsor
Jeeyun Lee
Study ID
NCT06085755
Phase
PHASE1/PHASE2
Status
Recruiting
Apply to this trial

Conditions

  • Stomach Neoplasm

Eligibility Criteria

Sex
ALL
Age
19 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Trastuzumab deruxtecan — DRUG
    Trastuzumab deruxtecan will be administered 6.4mg/kg or 5.4mg/kg iv infusion q 3weeks as one cycle.
  • Afatinib — DRUG
    Afatinib will be administered orally 20mg \~40mg once a day or three times a week(Monday, Wednesday, Friday \[MWF\]) or twice weekly (Monday, Thursday \[MT\]) for 3weeks as one cycle.

Study Details

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.

Key Dates

Start date
Sep 30, 2024
Status verified
Dec 2025
Primary completion
Dec 31, 2025
Completion
Dec 31, 2026

Study Design

Enrollment
61 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Trastuzumab deruxtecan + Afatinib
    The first part (PART A) will be in combination with T-DXd the starting dose of 20 mg afatinib MWF will be escalated to reach a maximum tolerated dose in patients with advanced gastric cancer patients with HER2-low, as defined by dose-limiting toxicity. The second part (PART B) will be expansion cohort, in which Afatinib will be taken in combination with T-DXd according to the recommended Phase 2 dose(RP2D) confirmed through Part A from cycle 1.

Primary Outcome Measure

Adverse events by NCI-CTCAE v5.0 [ Time Frame: through study completion, an average of 30 months ]

Central Contacts