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

NCT05163223 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: PN-301-21
• Study Type: interventional
• Target: 10
• Locations: 2 countries
• Sites: 17

Brief Summary

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).

Conditions

Breast Cancer

Keywords

HER 2 low (1+ or 2+ and non-amplified by FISH)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• AST-301 specific T cell immune responses

  Up to approximately 82 weeks

• Change in central memory T cell populations

  Up to approximately 82 weeks

• Distant Recurrence-Free Survival rate, dRFS rate

  Overall study period approximately up to 4 years

• Number of participants with treatment-related adverse events as assessed by CTCAE

  Overall study period approximately up to 4years

Study Arms (2)

AST-301(pNGVL3-hICD)+Chemotherapy

EXPERIMENTAL

* AST-301/rhuGM-CSF (q 3 weeks, 3 cycles) + Standard adjuvant therapy\* * A booster (AST-301/rhuGM-CSF) at 24 weeks post the third vaccination * Standard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)

Biological: AST-301(pNGVL3-hICD); Drug: rhuGM-CSF; Drug: Pembrolizumab; Drug: Capecitabine

Placebo + Chemotherapy

ACTIVE COMPARATOR

* Placebo/rhuGM-CSF (q 3 weeks, 3 cycles) + Standard adjuvant therapy\* * A booster (Placebo/rhuGM CSF) at 24 weeks post the third vaccination * Standard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)

Drug: rhuGM-CSF; Drug: Placebo; Drug: Pembrolizumab; Drug: Capecitabine

Interventions

AST-301(pNGVL3-hICD) BIOLOGICAL

Q3W, 3 cycles, Plus a booster at 24 weeks post the third vaccination, Intradermal injection

Also known as: AST-301

AST-301(pNGVL3-hICD)+Chemotherapy

rhuGM-CSF DRUG

Q3W, 3 cycles, Plus a booster at 24weeks post the third vaccination, Intradermal injection

Also known as: Leukine, Sargramostim

AST-301(pNGVL3-hICD)+Chemotherapy; Placebo + Chemotherapy

Placebo DRUG

Q3W, 3 cycles, Plus a booster at 24 weeks post the third vaccination, Intradermal injection

Also known as: Normal Saline

Placebo + Chemotherapy

Pembrolizumab DRUG

Q3W; IV infusion

Also known as: Keytruda

AST-301(pNGVL3-hICD)+Chemotherapy; Placebo + Chemotherapy

Capecitabine DRUG

On days 1-14 (Q3W), BID ; Oral administration,

Also known as: Xeloda

AST-301(pNGVL3-hICD)+Chemotherapy; Placebo + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Aston Sci. Inc.: lead

Study Sites (17)

Ironwood Cancer and Research Centers

Chandler, Arizona, 85224, United States

Location

Scripps Health

La Jolla, California, 92037, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

Nebraska Cancer Specialist

Omaha, Nebraska, 68130, United States

Location

Gabrail Cancer Center Research

Canton, Ohio, 44718, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43623, United States

Location

Toledo Clinic Cancer Center

Toledo, Ohio, 43623, United States

Location

Providence Cancer Institute

Portland, Oregon, 97213, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Changhua Christian Hospital

Changhua, 500, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 404, Taiwan

Location

Chi Mei Medical Center

Tainan, 710, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center

Taipei, 11259, Taiwan

Location

National Taiwan University Hospital

Taipei, 112, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

sargramostim; Saline Solution; pembrolizumab; Capecitabine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2021
• First Posted: December 20, 2021
• Study Start: February 28, 2022
• Primary Completion: May 31, 2024
• Study Completion: May 31, 2024
• Last Updated: June 17, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (7); US (10)