Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Gastric Cancer (Conerstone3)

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer
• Intervention / Treatment: Drug: AST-301; Drug: rhuGM-CSF

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Minghua Huang, MD; Phone Number: 82-2-2038-2347; Email: mhhwang@astonsci.com
• Study Contact Backup: Name: Hun Jung, MD, PhD; Phone Number: 82-2-2038-2347; Email: jhun@astonsci.com

Study Locations

• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
    • Contact: I-CHEN WU, MD
  • Taichung, Taiwan, 40705
    • Recruiting
    • Taichung Veterans General Hospital
    • Contact: SHAO-CIAO LUO, MD
  • Taichung, Taiwan, 404
    • Recruiting
    • China Medical University Hospital
    • Contact: LI-YUAN BAI, MD
  • Tainan, Taiwan, 710
    • Recruiting
    • Chi Mei Medical Center
    • Contact: YIN-HSUN FENG, MD
  • Taipei, Taiwan, 112
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: MING-HUANG CHEN, MD
  • Taoyuan, Taiwan, 333
    • Recruiting
    • Chang Gung Memorial Hospital LinKou
    • Contact: WEN-CHI CHOU, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Aston Sci. Inc.
• Investigators: Study Director: Hun Jung, MD, jhun@astonsci.com

Study record dates

Study Major Dates

• Study Start (Actual): July 4, 2023
• Primary Completion (Estimated): October 15, 2025
• Study Completion (Estimated): June 15, 2026

Study Registration Dates

• First Submitted: September 6, 2022
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 8, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Sargramostim
• Other Study ID Numbers: PN-301-22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes