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

Study Overview
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Brief Summary
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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
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Not provided

Official Title
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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)

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: AST-301(pNGVL3-hICD)
* Drug: rhuGM-CSF
* Drug: Placebo
* Drug: Pembrolizumab
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AST-301(pNGVL3-hICD)+Chemotherapy<br>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)<br>* Q3W, 3 cycles, Plus a booster at 24 weeks post the third vaccination, Intradermal injection<br>* Other names: AST-301;Drug: rhuGM-CSF<br>* Q3W, 3 cycles, Plus a booster at 24weeks post the third vaccination, Intradermal injection<br>* Other names: Sargramostim;Drug: Pembrolizumab<br>* Q3W; IV infusion<br>* Other names: Keytruda;Drug: Capecitabine<br>* On days 1-14 (Q3W), BID ; Oral administration,<br>* Other names: Xeloda;|
| Active Comparator: Placebo + Chemotherapy<br>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<br>* Q3W, 3 cycles, Plus a booster at 24weeks post the third vaccination, Intradermal injection<br>* Other names: Sargramostim;Drug: Placebo<br>* Q3W, 3 cycles, Plus a booster at 24 weeks post the third vaccination, Intradermal injection<br>* Other names: Normal Saline;Drug: Pembrolizumab<br>* Q3W; IV infusion<br>* Other names: Keytruda;Drug: Capecitabine<br>* On days 1-14 (Q3W), BID ; Oral administration,<br>* Other names: Xeloda;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER 2 low (1+ or 2+ and non-amplified by FISH)