Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Patients With Breast Cancer (Cornerstone001)

A Phase 2 Study to Evaluate the Efficacy and Safety of an Adjuvant Therapeutic Cancer Vaccine (AST-301, pNGVL3-hICD) in Patients With HER2 Low Breast Cancer (Cornerstone-001)

The purpose of this study is to evaluate the efficacy and safety of an adjuvant treatment of therapeutic cancer vaccine (AST-301, pNGVL3-hICD) in patients with HER2-low expression (IHC 1+ or 2+ and ISH-) and hormone receptor-negative(ER-, PR-) breast cancer with residual disease after neoadjuvant treatment.

Patients will be randomized 1:1 to either the Experimental arm (combination of AST-301/rhuGM CSF and standard adjuvant therapy) or the Control arm (combination of placebo/rhuGM CSF and standard adjuvant therapy). Standard adjuvant chemotherapy will be pembrolizumab or capecitabine.

Adjuvant therapy will be administered in compliance with the NCCN guideline for breast cancer (Version 8, 2021), and IP (AST-301) will be administered 3 times every 3 weeks in the adjuvant treatment period, with a booster administered at 24 weeks (±7 days) post the third dose of IP administration.

Survival follow up will be performed to determine invasive Disease Free survival(iDFS).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: AST-301(pNGVL3-hICD); Drug: rhuGM-CSF; Drug: Pembrolizumab; Drug: Capecitabine; Drug: Placebo

Detailed Description

Not provided

• Study Type: Interventional
• Enrollment (Estimated): 146
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eunkyo Joung, CMO; Phone Number: 02-2038-2347; Email: eunkyo.joung@astonsci.com
• Study Contact Backup: Name: Aston Sci. Inc,; Email: astonsci@astonsci.com

Study Locations

• Taiwan
  • Changhua City, Taiwan, 500
    • Recruiting
    • Changhua Christian Hospital
    • Contact: SHOU-TUNG CHEN, MD
  • Kaohsiung, Taiwan, 80756
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
    • Contact: MING-FENG HOU, MD
  • Taichung City, Taiwan, 404
    • Recruiting
    • China Medical University Hospital
    • Contact: LIANG-CHIH LIU, MD
  • Tainan, Taiwan, 710
    • Recruiting
    • Chi Mei Medical Center
    • Contact: NAI-WEN KANG, MD
  • Taipei City, Taiwan, 112
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: LING-MING TSENG, MD
  • Taipei City, Taiwan, 112
    • Recruiting
    • National Taiwan University Hospital
    • Contact: CHIUN-SHENG HUANG, MD
  • Taipei city, Taiwan, 11259
    • Recruiting
    • Koo Foundation Sun Yat-Sen Cancer Center
    • Contact: CHI-FENG CHUNG, MD
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Recruiting
      • Ironwood Cancer and Research Centers
      • Contact: KALMADI SUJITH, MD
  • California
    • La Jolla, California, United States, 92037
      • Not yet recruiting
      • Scripps Health
      • Contact: MOHAMMED JALOUDI, MD
  • Florida
    • Tampa, Florida, United States, 33612
      • Not yet recruiting
      • Moffitt Cancer Center
      • Contact: Aixa Soyano, MD
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • University of Illinois Cancer Center
      • Contact: VIJAYAKRISHNA GADI, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Nebraska Cancer Specialist
      • Contact: SARAH CREAMER, MD
  • Ohio
    • Canton, Ohio, United States, 44718
      • Recruiting
      • Gabrail Cancer Center Research
      • Contact: NASHAT Y GABRAIL, MD
    • Columbus, Ohio, United States, 43623
      • Not yet recruiting
      • The Ohio State University Comprehensive Cancer Center
      • Contact: Kai Johnson, MD
    • Toledo, Ohio, United States, 43623
      • Recruiting
      • Toledo Clinic Cancer Center
      • Contact: Rex Mowat, MD
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Cancer Institute
      • Contact: SASHA STANTON, MD
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • University of Washington
      • Contact: Mary Nora Disis, MD

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Has a residual invasive cancer in the breast(non-pCR) after neoadjuvant treatment
• Has stage I, II, or III disease prior to surgery per American Joint Committee on Cancer (AJCC)
• HER 2 1+ by IHC or HER2 2+by IHC without gene amplification by ISH, as defined by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• Hormone receptor (ER and PR) negative by ASCO/CAP guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Demonstrates adequate organ function.

Key Exclusion Criteria:

• Has a history of hypersensitivity or other contraindications to rhGM-CSF
• Has a history of invasive malignancy ≤5 years prior to first administration of investigational drug except for adequately treated non-melanoma skin cancer or carcinoma in situ.
• Is on immune suppression therapy or has a history of immune suppression therapy ≤4 weeks prior to the first administration of investigational drugs
• 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: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AST-301(pNGVL3-hICD)+Chemotherapy; AST-301/rhuGM-CSF (q 3 weeks, 3 cycles) + Standard adjuvant therapy*; A booster (AST-301/rhuGM-CSF) at 24 weeks post the third vaccinationStandard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)	Biological: AST-301(pNGVL3-hICD); Q3W, 3 cycles, Plus a booster at 24 weeks post the third vaccination, Intradermal injection; Other Names: AST-301; Drug: rhuGM-CSF; Q3W, 3 cycles, Plus a booster at 24weeks post the third vaccination, Intradermal injection; Other Names: Leukine; Sargramostim; Drug: Pembrolizumab; Q3W; IV infusion; Other Names: Keytruda; Drug: Capecitabine; On days 1-14 (Q3W), BID ; Oral administration,; Other Names: Xeloda
Active Comparator: Placebo + Chemotherapy; Placebo/rhuGM-CSF (q 3 weeks, 3 cycles) + Standard adjuvant therapy*; A booster (Placebo/rhuGM CSF) at 24 weeks post the third vaccinationStandard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)	Drug: rhuGM-CSF; Q3W, 3 cycles, Plus a booster at 24weeks post the third vaccination, Intradermal injection; Other Names: Leukine; Sargramostim; Drug: Pembrolizumab; Q3W; IV infusion; Other Names: Keytruda; Drug: Capecitabine; On days 1-14 (Q3W), BID ; Oral administration,; Other Names: Xeloda; Drug: Placebo; Q3W, 3 cycles, Plus a booster at 24 weeks post the third vaccination, Intradermal injection; Other Names: Normal Saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year invasive disease free survival rate (iDFS)	iDFS event is defined as Ipsilateral breast tumor recurrence Local/regional invasive recurrence Distant recurrence Invasive contralateral breast cancer Death (from breast cancer/non-breast cancer cause/unknown cause) Secondary primary invasive cancer (non-breast)	Overall study period approximately up to 4years (End of study in this study is defined as 2years frm the date of last Patient In.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AST-301 specific T cell immune responses	Immune response will be assessed by IFN-gamma enzyme-linked immune absorbent spot (ELISpot) assay	Up to approximately 82 weeks
Change in central memory T cell populations	Assessment by FACS	Up to approximately 82 weeks
Distant Recurrence-Free Survival rate, dRFS rate	dRFS rate at the end of study	Overall study period approximately up to 4 years
Number of participants with treatment-related adverse events as assessed by CTCAE	To assess safety of AST-301 administered in breast cancer patients.	Overall study period approximately up to 4years

Collaborators and Investigators

• Sponsor: Aston Sci. Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2022
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 2, 2021
• First Submitted That Met QC Criteria: December 6, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): July 20, 2023
• Last Update Submitted That Met QC Criteria: July 18, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: HER 2 low (1+ or 2+ and non-amplified by FISH)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Capecitabine; Pembrolizumab; Sargramostim
• Other Study ID Numbers: PN-301-21

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