GLSI-100 for HER2 Positive Breast Cancer

(FLAMINGO-01 Trial)

Recruiting at 279 trial locations

Overseen By Stephani Christensen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 3

Sponsor: Greenwich LifeSciences, Inc.

Must be taking: Trastuzumab

Must not be taking: Chemotherapy, Corticosteroids

Disqualifiers: Stage IV cancer, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 12

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new immunotherapy called GLSI-100 to determine if it can prevent breast cancer recurrence in individuals with HER2/neu positive breast cancer. Participants receive several injections over three years, with the new treatment compared to a placebo (a substance with no active drug). The trial includes those who have completed standard cancer treatments but remain at high risk of recurrence. Individuals with HER2/neu positive breast cancer, who show no signs of active cancer and have finished their initial therapies, might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving chemotherapy, investigational agents, or long-term systemic treatment with corticosteroids or other immunosuppressive therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GLSI-100 is generally well-tolerated. In one study with breast cancer patients, those treated with GLSI-100 experienced an 80% or greater reduction in cancer recurrences, suggesting the treatment is effective and safe for most patients.

Although specific side effects were not listed, GLSI-100's Phase 3 study status indicates that extensive safety information has been gathered from earlier stages. This suggests any side effects are manageable or not serious enough to halt the trial.

Additionally, GLSI-100 has received Fast Track designation from the FDA, indicating that the treatment is considered safe and has the potential to meet important medical needs. For those considering joining a trial, these points offer reassurance about the treatment's safety in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about GLSI-100 because it offers a novel approach to treating HER2/neu-positive cancers. Unlike standard treatments, which typically involve monoclonal antibodies like trastuzumab or chemotherapy, GLSI-100 is an immunotherapy that combines a peptide vaccine (GP2) with an immune-boosting agent (GM-CSF). This treatment is administered intradermally, which is a less invasive method compared to traditional intravenous therapies. By harnessing the body's immune system to specifically target and destroy cancer cells, GLSI-100 has the potential to enhance treatment effectiveness and reduce side effects associated with conventional therapies.

What evidence suggests that this trial's treatments could be effective for high-risk HER2/neu positive patients?

In a previous study, GLSI-100 showed promising results in reducing cancer recurrence for patients with high levels of HER2/neu, a protein linked to some breast cancers. After five years, those who received the treatment experienced an 80% or greater reduction in cancer recurrences. This trial will evaluate GLSI-100 in two separate arms: one for HLA-A*02 positive and HER2/neu positive subjects, and an open-label arm for non-HLA-A*02 positive and HER2/neu positive subjects. Additionally, GLSI-100 was found to be safe and showed signs of activity in fighting cancer in patients with high HER2 levels. Overall, these findings provide strong evidence that GLSI-100 might help prevent the return of cancer in certain patients. ^{6 7 8 9 10}

Who Is on the Research Team?

Mothaffar Rimawi, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

Inclusion Criteria

I have completed all recommended treatments for breast cancer that included trastuzumab.

My cancer was stage I, II, or III and still present after initial treatment, or it was stage III but fully treated with initial therapy.

My doctor has found no signs of remaining breast cancer.

Exclusion Criteria

I have no other cancers except possibly treated skin cancer or cervical cancer.

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.

I have had severe allergic reactions to certain medications or components.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Primary Immunization Series (PIS)

Participants receive 6 intradermal injections of GLSI-100 or placebo over the first 6 months

6 months

6 visits (in-person)

Booster Injections

Participants receive 5 booster intradermal injections spaced 6 months apart

2.5 years

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 years

Interim analysis planned

What Are the Treatments Tested in This Trial?

Interventions

• GLSI-100
• Placebo

How Is the Trial Designed?

Group I: GLSI-100, Open-label Experimental Treatment 1 Intervention

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)

Group II: GLSI-100 Experimental Treatment 1 Intervention

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)

Group III: 0.9% Normal Saline Placebo Group 1 Intervention

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)

Who Is Running the Clinical Trial?

Greenwich LifeSciences, Inc.

Lead Sponsor

Trials

1

Recruited

750+

Published Research Related to This Trial

Hyperimmunization with the Id-GM-CSF fusion protein successfully induced anti-GM-CSF antibodies that could neutralize GM-CSF's activity in vitro, but did not negatively impact the overall health or white blood cell counts of the mice involved in the study.

A new strategy was developed to avoid the induction of anti-GM-CSF antibodies by using a priming dose of Id-GM-CSF followed by a boost with the Id protein alone, which still generated strong immune responses without the unwanted neutralizing antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of autoantibody responses to GM-CSF by hyperimmunization with an Id-GM-CSF fusion protein. Chen, TT., Levy, R.[2013]

In a study of 56 cancer patients, switching from granulocyte colony-stimulating factor (G-CSF) to granulocyte-macrophage CSF (GM-CSF) resulted in a higher frequency of febrile neutropenia and chemotherapy dose delays, indicating that GM-CSF may be less effective in preventing neutropenic events.

Patients treated with GM-CSF experienced more adverse events and required greater medical resources, such as transfusions and hospitalizations, compared to those treated with G-CSF, suggesting that G-CSF is the safer and more effective option for managing chemotherapy-induced neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a formulary change from granulocyte colony-stimulating factor to granulocyte-macrophage colony-stimulating factor on outcomes in patients treated with myelosuppressive chemotherapy. Wong, SF., Chan, HO.[2018]

In a study involving 35 patients (18 receiving GM-CSF and 17 controls), GM-CSF did not enhance T cell or natural killer cell recovery after allogeneic stem cell transplantation, contrary to expectations.

However, GM-CSF administration improved dendritic cell reconstitution in patients undergoing autologous stem cell transplantation, suggesting its benefits may vary based on the type of transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granulocyte-macrophage colony-stimulating factor increases the proportion of circulating dendritic cells after autologous but not after allogeneic hematopoietic stem cell transplantation. Eksioglu, EA., Kielbasa, J., Eisen, S., et al.[2018]

Granulocyte macrophage-colony stimulating factor (GM-CSF) plays a crucial role in the proliferation and differentiation of immune cells, particularly granulocytes and macrophages, indicating its importance in immune response regulation.

Preclinical studies suggest that targeting GM-CSF could be a promising therapeutic strategy for treating various inflammatory and autoimmune disorders, such as rheumatoid arthritis, with ongoing clinical trials exploring GM-CSF blockade in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GM-CSF: A Promising Target in Inflammation and Autoimmunity. Lee, KMC., Achuthan, AA., Hamilton, JA.[2020]

In a study involving 133 cancer patients, a single dose of GM-CSF given alongside the influenza vaccine did not enhance the immune response, as measured by hemagglutination inhibition assay titers.

The analysis indicated that the placebo group had a slightly better response to the vaccine, suggesting that GM-CSF does not improve vaccination efficacy in this population, particularly as response rates decline with age and higher initial antibody levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of influenza vaccine with granulocyte-macrophage colony-stimulating factor or placebo in cancer patients. Ramanathan, RK., Potter, DM., Belani, CP., et al.[2016]

CSL324, a fully human therapeutic anti-G-CSFR antibody, was found to be safe and well tolerated in cynomolgus macaques, effectively controlling G-CSF-mediated neutrophilia without causing neutropenia, even at high doses over extended periods.

The treatment did not affect normal neutrophil functions like phagocytosis and oxidative burst, suggesting that targeting G-CSFR could be a safe and effective strategy for managing neutrophilia in inflammatory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A neutralizing anti-G-CSFR antibody blocks G-CSF-induced neutrophilia without inducing neutropenia in nonhuman primates. Scalzo-Inguanti, K., Monaghan, K., Edwards, K., et al.[2018]

GM-CSF can enhance the immune response to cancer vaccines when given in low doses (40-80 micrograms for 1-5 days), but higher doses (100-500 micrograms) may lead to immune suppression, as shown in various clinical trials and animal studies.

The mixed results in clinical trials suggest that while GM-CSF can be beneficial as an adjuvant in cancer vaccination, its effects can vary significantly based on dosage, potentially due to the activation of myeloid suppressor cells that inhibit immune responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients. Parmiani, G., Castelli, C., Pilla, L., et al.[2020]

In a study involving cynomolgus monkeys, the human granulocyte colony-stimulating factor (hG-CSF) derivative KW-2228 demonstrated strong granulopoietic activity and maintained low antibody levels over multiple treatment courses, indicating its potential as a safer alternative to intact hG-CSF.

In contrast, the derivatives NC-59 and M-7 showed decreased effectiveness and increased antibody responses after repeated administration, suggesting that modifications to the N-terminal amino acids can impact both efficacy and immunogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo effect of human granulocyte colony-stimulating factor derivatives on hematopoiesis in primates. Kato, Y., Yamamoto, M., Ikenaga, T., et al.[2018]

Recombinant human GM-CSF has been shown to effectively reduce granulocytopenia depth and duration in patients undergoing cancer chemotherapy and bone marrow transplantation, leading to increased marrow cellularity and improved leukocyte responses.

The use of GM-CSF is associated with a lower incidence of infections compared to historical controls, suggesting it may enhance chemotherapy delivery and improve patient outcomes, although further large-scale studies are needed to confirm its impact on morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of granulocyte-macrophage colony-stimulating factor in iatrogenic myelosuppression, bone marrow failure, and regulation of host defense. Gutterman, J., Vadhan-Raj, S., Logothetis, C., et al.[2021]

Recombinant human GM-CSF significantly increased monocyte numbers in rhesus macaques by an average of 32-fold, indicating its potential as an adjuvant to enhance immune responses in vaccine studies.

However, the development of neutralizing antibodies against human GM-CSF after initial treatment suggests that species-specific GM-CSF is necessary for effective immunomodulation in primates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of neutralising antibodies restricts the use of human granulocyte/macrophage colony stimulating factor for vaccine studies in rhesus macaques. Eisenblätter, M., Stahl-Hennig, C., Kuate, S., et al.[2007]

Granulocyte colony-stimulating factor (G-CSF) has been shown to effectively reduce the duration of severe neutropenia and lower the risk of infections in patients undergoing cytotoxic chemotherapy, with minimal associated toxicity.

Granulocyte macrophage colony-stimulating factor (GM-CSF) increases various white blood cell types in patients with conditions like AIDS and aplastic anemia, but its use is limited by dose-related toxicity, with maximum tolerated doses ranging from 16 to 32 micrograms/kg/day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of the myeloid growth factors. Glaspy, JA., Golde, DW.[2017]

GM-CSF is effective in preventing or reversing neutropenia, with a recommended dose of 5-10 micrograms/kg/day administered via intravenous infusion or subcutaneous injection, leading to predominantly mild-to-moderate side effects in 20-30% of patients.

High doses of GM-CSF can cause severe adverse effects, including a 'first-dose reaction' in some patients, but with careful monitoring and appropriate dosing, the overall benefit-to-risk ratio has significantly improved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The side-effect profile of GM-CSF. Stern, AC., Jones, TC.[2019]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.17_suppl.LBA550

Evaluation of booster injections in maintaining peak ... Boosters were administered to 53 HER2 3+ patients (54%). The median peak ISR during the PIS in GLSI-100 treated patients was 92.1 mm versus 60.5 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05232916

NCT05232916 | Phase 3 Study to Evaluate the Efficacy ... Phase 3 Study to Evaluate the Efficacy and Safety of HER2/​Neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/​Neu Positive Subjects (FLAMINGO-01). ClinicalTrials ...

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P5-07-22/752663/Abstract-P5-07-22-Phase-III-study-to-evaluate-the

Phase III study to evaluate the efficacy and safety of GLSI-100 ... Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5323226/

Primary analysis of a prospective, randomized, single- ... This trial confirmed that the GP2 vaccine is safe and suggests that vaccination may have clinical activity, particularly in patients with HER2 overexpression.

5. greenwichlifesciences.com greenwichlifesciences.com/clinical-trials/completed-phase-iib-clinical-trial/

Completed Phase IIb Clinical Trial After 5 years of follow-up, there was an 80% or greater reduction in cancer recurrences in the HER2/neu 3+ patients who were treated with GLSI-100 and, followed ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS618

Phase III study to evaluate the efficacy and safety of GLSI ... Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05232916

NCT05232916 | Phase 3 Study to Evaluate the Efficacy ... 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 ...

8. investor.greenwichlifesciences.com investor.greenwichlifesciences.com/news-events/press-releases/detail/94/label-safety-data-from-flamingo-01

Greenwich LifeSciences Provides Update on Open Label ... After 5 years of follow-up, there was an 80% or greater reduction in cancer recurrences in the HER2/neu 3+ patients who were treated with GLSI- ...

9. esmoopen.com esmoopen.com/article/S2059-7029(23)00572-0/fulltext

122TiP Phase III study to evaluate the efficacy and safety of ... 122TiP Phase III study to evaluate the efficacy and safety of GLSI-100 (GP2 + GM-CSF) in breast cancer patients with residual disease or high-risk PCR after ...

10. onclive.com onclive.com/view/fda-grants-fast-track-designation-to-glsi-100-in-hla-a-02-her2-breast-cancer

FDA Grants Fast Track Designation to GLSI-100 in HLA-A* ... GLSI-100 targets HLA-A*02-positive, HER2-positive breast cancer, aiming to improve invasive breast cancer–free survival post-standard therapy.