Phase 3 Study to Evaluate the Efficacy and Safety of HER2/Neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/Neu Positive Subjects

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blinded, placebo-controlled, multi-center, Phase 3 study of GLSI-100 immunotherapy in HLA-A*02 positive and HER2/neu positive subjects who are at high risk for disease recurrence and have completed both neoadjuvant and postoperative adjuvant standard of care therapy. Treatment consists of 6 intradermal injections, Primary Immunization Series (PIS), over the first 6 months of treatment and 5 booster intradermal injections spaced 6 months apart. A third open-label arm will explore GLSI-100 immunotherapy in non-HLA-A*02 positive and HER2/neu positive subjects.

Official Title
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A Randomized, Multicenter, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of HER2/Neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/Neu Positive Subjects With Residual Disease or High-Risk PCR After Both Neoadjuvant and Postoperative Adjuvant Trastuzumab-based Therapy (FLAMINGO-01)

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: Placebo
* Biological: GLSI-100


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HLA-A*02-positive, unless being enrolled in the third non-HLA-A*02 arm Histologically confirmed diagnosis of HER2/neu positive primary breast cancer Completion of both neoadjuvant and adjuvant trastuzumab-based standard of care breast cancer therapy Stage I, II, or III at presentation with pathologic evidence of residual invasive carcinoma in the breast or axillary lymph nodes (residual disease) at surgery following completion of neoadjuvant therapy -OR- Stage III at presentation with pathologic complete response (pCR) at surgery following completion of neoadjuvant therapy The subject can begin study therapy within one year of completion of adjuvant trastuzumab-based therapy and any other standard therapies, but, study therapy can be administered concurrently with endocrine therapy. No clinical evidence of residual or persistent breast cancer per treating physician assessment ECOG 0-2 Adequate organ function Negative pregnancy test or evidence of post-menopausal status If of childbearing potential, willing to use a form of highly effective contraception Exclusion Criteria: Stage IV cancer or metastatic breast cancer at any time Inflammatory breast cancer Receiving other investigational agents Receiving chemotherapy Requiring long-term systemic treatment with corticosteroids or other immunosuppressive therapy History of immunodeficiency or active autoimmune disease A history of serious allergic reactions, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factors such as sargramostim, yeast-derived products, or any component of the investigational product Other malignancies except adequately treated in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin Active infection Known HIV infection with a detectable viral load within 6 months of the anticipated start of treatment. Note: Subjects on effective antiretroviral therapy with an undetectable viral load within 6 months of the anticipated start of treatment are eligible for this trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: HLA-A*02 subjects will be randomized to GLSI-100 or placebo. Treatment consists of 6 intradermal injections, Primary Immunization Series (PIS), over the first 6 months of treatment and 5 booster intradermal injections spaced 6 months apart. A third open-label arm will explore GLSI-100 immunotherapy in non-HLA-A*02 positive and HER2/neu positive subjects.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 0.9% Normal Saline<br>0.9% normal saline in HLA-A*02 positive and HER2/neu positive subjects administered intradermally every month for first 6 months then every 6 months for next 2.5 years (11 intradermal injections over 3 years) | Biological: Placebo<br>* 0.9% Normal Saline<br>|
| Experimental: GLSI-100<br>GLSI-100 immunotherapy in HLA-A*02 positive and HER2/neu positive subjects administered intradermally every month for first 6 months then every 6 months for next 2.5 years (11 intradermal injections over 3 years) | Biological: GLSI-100<br>* 500 mcg/mL GP2 and 125 mcg/mL GM-CSF<br>|
| Experimental: GLSI-100, Open-label<br>Open-label arm: GLSI-100 immunotherapy in non-HLA-A*02 positive and HER2/neu positive subjects administered intradermally every month for first 6 months then every 6 months for next 2.5 years (11 intradermal injections over 3 years) | Biological: GLSI-100<br>* 500 mcg/mL GP2 and 125 mcg/mL GM-CSF<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Breast Cancer-free Survival (IBCFS) | IBCFS is defined as the time from the first dose of study medication until the date of ipsilateral invasive breast cancer recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, or any cause mortality. | Median 4 years of follow-up (interim analysis planned) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease-free Survival (IDFS) | IDFS is defined as the time from the first dose of study medication until the date of ipsilateral invasive breast cancer recurrence, ipsilateral local-regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, or any cause mortality. | Median 4 years of follow-up (interim analysis planned) | 
| Distant Disease-free Survival (DDFS) | DDFS will be defined as the time from the first dose of study medication to the time of distant disease recurrence or death. | Median 4 years of follow-up (interim analysis planned) | 
| Overall Survival | Overall survival will be defined as the time from the first dose of study medication until death from any cause. | Median 4 years of follow-up (interim analysis planned) | 
| Quality of Life Questionnaire Core 30 (QLQ-C30) | European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) | Baseline and 36 months | 
| Quality of Life FACT-GP5 | FACT-GP5 to assess global side effect impact | Baseline and 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2/neu positive, Residual disease, pCR, Extended adjuvant, GP2, Immunotherapy, HLA type