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)
Overview
- Phase
- Phase 2
- Intervention
- AST-301(pNGVL3-hICD)
- Conditions
- Breast Cancer
- Sponsor
- Aston Sci. Inc.
- Enrollment
- 10
- Locations
- 17
- Primary Endpoint
- 2-year invasive disease free survival rate (iDFS)
- Status
- Terminated
- Last Updated
- last year
Overview
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).
Detailed Description
Not provided
Investigators
Eligibility Criteria
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.
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
Arms & Interventions
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 vaccination * Standard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)
Intervention: AST-301(pNGVL3-hICD)
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 vaccination * Standard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)
Intervention: rhuGM-CSF
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 vaccination * Standard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)
Intervention: Pembrolizumab
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 vaccination * Standard adjuvant therapy will be pembrolizumab or capecitabine (q 3 weeks)
Intervention: Capecitabine
Placebo + Chemotherapy
* 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)
Intervention: rhuGM-CSF
Placebo + Chemotherapy
* 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)
Intervention: Placebo
Placebo + Chemotherapy
* 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)
Intervention: Pembrolizumab
Placebo + Chemotherapy
* 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)
Intervention: Capecitabine
Outcomes
Primary Outcomes
2-year invasive disease free survival rate (iDFS)
Time Frame: Overall study period approximately up to 4years (End of study in this study is defined as 2years frm the date of last Patient In.
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)
Secondary Outcomes
- Change in central memory T cell populations(Up to approximately 82 weeks)
- Number of participants with treatment-related adverse events as assessed by CTCAE(Overall study period approximately up to 4years)
- Distant Recurrence-Free Survival rate, dRFS rate(Overall study period approximately up to 4 years)
- AST-301 specific T cell immune responses(Up to approximately 82 weeks)