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 Trial)

Recruiting in Palo Alto (17 mi)

+229 other locations

Overseen by Mothaffar Rimawi, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the treatment GLSI-100, which includes GM-CSF, in clinical trials?

Research shows that GM-CSF, a component of GLSI-100, can enhance immune responses when used at low doses in cancer vaccine trials, although results have been mixed. It has also been found to reduce infection rates in patients undergoing cancer treatment by boosting white blood cell production. ^{1 2 3 4 5}

Is GLSI-100 (GP2 + GM-CSF) safe for humans?

GM-CSF, a component of GLSI-100, is generally safe when used at appropriate doses, with mild to moderate side effects like fever and rash in 20-30% of patients. High doses can cause more severe reactions, so careful monitoring is needed, especially in certain patient groups. ^{6 7 8 9 10}

How does the drug GLSI-100 differ from other treatments for this condition?

GLSI-100 is unique because it includes GM-CSF, which can enhance immune responses by increasing certain immune cells, but its effects can vary depending on the dosage and frequency of administration. This makes it different from other treatments that may not use GM-CSF as an adjuvant to boost the immune system. ^{1 2 9 11 12}

Research Team

Mothaffar Rimawi, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• GLSI-100 (Cancer Vaccine)
• Placebo (Other)

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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 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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

GM-CSF: A Promising Target in Inflammation and Autoimmunity. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized trial of influenza vaccine with granulocyte-macrophage colony-stimulating factor or placebo in cancer patients. [2016]

4. United States pubmed.ncbi.nlm.nih.gov

Induction of autoantibody responses to GM-CSF by hyperimmunization with an Id-GM-CSF fusion protein. [2013]

5. United States pubmed.ncbi.nlm.nih.gov

Effects of granulocyte-macrophage colony-stimulating factor in iatrogenic myelosuppression, bone marrow failure, and regulation of host defense. [2021]

6. England pubmed.ncbi.nlm.nih.gov

A neutralizing anti-G-CSFR antibody blocks G-CSF-induced neutrophilia without inducing neutropenia in nonhuman primates. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

The side-effect profile of GM-CSF. [2019]

8. United States 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. [2018]

9. Switzerland pubmed.ncbi.nlm.nih.gov

In vivo effect of human granulocyte colony-stimulating factor derivatives on hematopoiesis in primates. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Clinical applications of the myeloid growth factors. [2017]

11. Netherlands 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. [2007]

12. England 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. [2018]