Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Gastric Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 2 Study to Evaluate the Safety and Immunological Efficacy of Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Patients With HER2 Expressing Gastric Cancer (CORNERSTONE-003)

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: AST-301
* Drug: rhuGM-CSF


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Phase 2, open label, randomized, early proof-of-concept study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Total 300 μg of AST-301<br>AST-301/rhuGM-CSF (3-week interval, 3 cycles in total) | Drug: AST-301<br>* 100 μg<br>* Other names: pNGVL3-hICD;Drug: rhuGM-CSF<br>* 100 μg<br>* Other names: Sargramostim;|
| Experimental: Total 600 μg of AST-301<br>AST-301/rhuGM-CSF (3-week interval, 6 cycles in total) | Drug: AST-301<br>* 100 μg<br>* Other names: pNGVL3-hICD;Drug: rhuGM-CSF<br>* 100 μg<br>* Other names: Sargramostim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | To assess the safety of AST-301 administered in gastric cancer patients. | up to 20 weeks | 
| Immunologic efficacy of AST-301 immunization | AST-301 specific interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISpot) assay | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1year Disease-Free Survival rate (DFS rate) | disease free survival rate at 1 year | 12 months | 
| Disease-Free Survival rate (DFS rate) at end of study (EOS) | disease free survival at end of study | Overall study period approximately 31 months | 
| Compare immunogenicity of AST-301 between Arm 1 and Arm 2 | AST-301-specific IFN γ response by ELISpot assay | 52 weeks | 
| Change in central memory T-cell populations between Arm 1 and Arm 2 | Central memory T-cell (cluster of differentiation 4 (CD4) + and cluster of differentiation 8 (CD8) +) by a flow cytometry analysis | 52 weeks |