Gastric Cancer
Conditions
Brief summary
The purpose of this early proof-of-concept study to evaluate the safety and immunologic efficacy of AST-301 in gastric cancer patients with HER2 expression (including both HER2 low expression and overexpression) who have completed the standard adjuvant treatment (including those who discontinued the standard adjuvant treatment due to intolerance). Participants will be randomized 1:1 to either Arm 1 (Q3W, 3 cycles), or Arm 2 (Q3W, 6 cycles) of the study. Safety Monitoring Committee (SMC) will oversee safety of study at 25% (6 participants), 50% (12 participants), and 75% (18 participants) of participants receive at least 1 dose of AST-301 and survival follow up will be performed to determine disease-free survival (DFS).
Detailed description
Participants will provide informed consent and will undergo Pre-Screening/Screening procedures before taking part in the study. Participants will be in Arm 1 and Arm 2 will be conducted in parallel. AST-301 will be administrated every 3 weeks for a total of 3 immunizations in Arm 1 and a total of 6 immunizations in Arm 2. * Arm 1: 3 immunizations of AST-301 admixed with immunoadjuvant recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) administered at 3-week intervals. (Total 300 μg of AST-301) * Arm 2: 6 immunizations of AST-301 admixed with immunoadjuvant recombinant human granulocyte-macrophage colony stimulating factor (rhuGM-CSF) administered at 3-week intervals. (Total 600 μg of AST-301) Randomization will be stratified according to HER2 expression (HER2 low expression or HER2 overexpression). For both Arm 1 and Arm 2 of the study there will be a Pre-screen period, followed by study periods: a Screening Period (Day -28 to Day -1), a Treatment Period (3 cycles/Arm 1 and 6 cycles/Arm 2), an end of treatment (EOT) visit and follow-up visits.
Interventions
DRUGAST-301
100 μg
DRUGrhuGM-CSF
100 μg
Sponsors
Aston Sci. Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 2, open label, randomized, early proof-of-concept study
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Underwent a curative surgery with standard lymph node dissection (confirmed with no residual tumor, R0 resection) and have completed standard adjuvant treatment * Has stages II or III according to the 8th edition of the American Joint Committee on Cancer (AJCC) * HER2 low expression and HER2 overexpression diagnosed according to the 2016 College of American Pathologists (CAP)/American Society for Clinical Pathology (ASCP)/American Society of Clinical Oncology (ASCO) guidelines * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 * Demonstrates adequate organ function. Key
Exclusion criteria
* Has a history of hypersensitivity or other contraindications to rhuGM-CSF * Has a history of other malignancies ≤5 years prior to first administration of Investigational Product (IP) except for adequately treated non-melanoma skin cancer or epithelial carcinoma without evidence of disease. * Has received systemic immunosuppressants or were treated with systemic immunosuppressants ≤4 weeks prior to the first administration of Investigational Product (IP). * Has a history of autoimmune disease or inflammatory disease * Has active infection including tuberculosis, hepatitis B, hepatitis C or human immunodeficiency virus (HIV) infection * Is pregnant or breastfeeding or expecting to conceive children
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0. | up to 20 weeks | To assess the safety of AST-301 administered in gastric cancer patients. |
| Immunologic efficacy of AST-301 immunization | 52 weeks | AST-301 specific interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISpot) assay |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1year Disease-Free Survival rate (DFS rate) | 12 months | disease free survival rate at 1 year |
| Disease-Free Survival rate (DFS rate) at end of study (EOS) | Overall study period approximately 31 months | disease free survival at end of study |
| Compare immunogenicity of AST-301 between Arm 1 and Arm 2 | 52 weeks | AST-301-specific IFN γ response by ELISpot assay |
| Change in central memory T-cell populations between Arm 1 and Arm 2 | 52 weeks | Central memory T-cell (cluster of differentiation 4 (CD4) + and cluster of differentiation 8 (CD8) +) by a flow cytometry analysis |
Countries
Taiwan
Contacts
STUDY_DIRECTORHun Jung, MD
jhun@astonsci.com
Outcome results
None listed