NCT06085755

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

Ph 1/2 Study of Trastuzumab Deruxtecan(T-DXd) and Afatinib Combination in HER2-low Advanced Gastric Cancer(VIKTORY-2)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 61 (estimated)
• Sponsor: Jeeyun Lee · Academic / Other
• Sex: All
• Age: 19 Years
• Healthy volunteers: Not accepted

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/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.

Detailed description

Patients who 2nd and 3rd line and expected propositions with histologically confirmed metastatic and/or recurrent gastric adenocarcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion according to the RECIST 1.1 are eligible. Adequate hematologic function, hepatic function, and renal function are required. Patients with other concurrent uncontrolled medical diseases and/or other tumors are also excluded. 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. PK samples will be collected at designated points, in both Part A and Part B. Tumor evaluation using modified RECIST 1.1 will be conducted at screening (within 28 days prior to first dose) and every 6 weeks relative to the date of first dose, up to week 40, then every 12 weeks until objective disease progression.

Conditions

• Stomach Neoplasm

Interventions

Type	Name	Description
DRUG	Trastuzumab deruxtecan	Trastuzumab deruxtecan will be administered 6.4mg/kg or 5.4mg/kg iv infusion q 3weeks as one cycle.
DRUG	Afatinib	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.

Timeline

• Start date: 2024-09-30
• Primary completion: 2025-12-01
• Completion: 2026-12-01
• First posted: 2023-10-17
• Last updated: 2025-12-15

Locations

1 site across 1 country: South Korea