Ignite Creation Date:
2024-05-06 @ 7:39 PM
Last Modification Date:
2024-10-26 @ 3:11 PM
Study NCT ID:
NCT06085755
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-14
First Post:
2023-09-10
Brief Title:
Trastuzumab DeruxtecanT-DXd and Afatinib Combination in HER2-low Advanced Gastric Cancer
Sponsor:
Jeeyun Lee
Organization:
Samsung Medical Center
Study Overview
Official Title:
Ph 12 Study of Trastuzumab DeruxtecanT-DXd and Afatinib Combination in HER2-low Advanced Gastric CancerVIKTORY-2
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 52 months in the ramucirumab group versus 38 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 64 mgkg T-DXd further demonstrated clinically meaningful efficacy The median OS was 125 months for the T-DXd group and 89 months for the physicians choice group HR 060 95 CI 042 086 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 IⅡ open-label single center study of afatinib in combination with T-DXd in 2L3L 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
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 64 mgkg T-DXd further demonstrated clinically meaningful efficacy The median OS was 125 months for the T-DXd group and 89 months for the physicians choice group HR 060 95 CI 042 086 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 IⅡ open-label single center study of afatinib in combination with T-DXd in 2L3L 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 andor recurrent gastric adenocarcinoma an Eastern Cooperative Oncology Group performance status of 0 or 1 and at least one measurable lesion according to the RECIST 11 are eligible Adequate hematologic function hepatic function and renal function are required Patients with other concurrent uncontrolled medical diseases andor 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 doseRP2D 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 11 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
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 doseRP2D 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 11 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None