FDA Lifts Clinical Hold on Phase 3 Study of GLSI-100 in HER2/Neu+ Breast Cancer

The FDA has removed the clinical hold on the phase 3 FLAMINGO-01 clinical trial (NCT05232916), which is evaluating the use of the HER2-/neu peptide GLSI-100 as treatment of patients with HER2/neu-positive primary breast cancer, according to an announcement by Greenwich LifeSciences, Inc.¹

The clinical hold was placed due to concerns about the manufacturing and pharmacy process for GLSI-100. Discussions between Greenwich LifeSciences, Inc. and the FDA, as well as testing of the GP2 in the pharmacy process have addressed the FDA’s initial concern. Additional testing of the pharmacy process will be conducted by the company. Clinical trial site visits have been initiated and further updates on the FLAMINGO-01 trial will be reported at a later date, according to the company.

FLAMINGO-01 is a randomized, multicenter, placebo-controlled, phase 3 study evaluating the efficacy and safety of GLSI-100. The primary end point of the study is invasive breast cancer-free survival and the secondary end points include invasive disease-free survival, distant disease-free survival, overall survival, and quality of life. The study will also explore immune response measurement between month 1 and 48.²

The study will include 3 treatment arms. In the first experimental arm, immunotherapy with GLSI-100 500 mcg/mL GP2 and 125 mcg/ML granulocyte-macrophage colony-stimulating factor (GM-CSF) will be administered intradermally to patients with HLA-A*02-positive and HER2/neu-positive breast cancer. The dosing schedule for GLSI-100 in the first experimental arm will be every month for the first 6 months followed by every 6 months for the next 2.5 years.

In the second experimental arm, the same dose of GLSI-100 will be administered to patients with non-HLA-A*02 positive and HER2/neu-positive breast. The second experimental arm will also follow the same dosing schedule as the first. In the comparator arm, patients with HLA-A*02-positive and HER2/neu-positive breast cancer will receive 0.9% normal saline intradermally every month for first 6 months, then every 6 months for next 2.5 years.

To be eligible for inclusion in the study, patients are required to have HLA-A*02-positive disease unless they are being enrolled in the third non-HLA-A*02 arm. Patients must also have histologically confirmed disease, no clinical evidence of residual or persistent breast cancer, an ECOG performance status of 0-2, adequate organ function, and be stage I-III at presentation. Female patients must have a negative pregnancy test or evidence of post-menopausal status. All patients must agree to use contraception during the study.

FLAMINGO-01 prohibits the enrollment of patients with stage IV cancer or metastatic breast cancer. In addition, patients with inflammatory breast cancer, history of immunodeficiency, or active autoimmune disease, history of serious allergic reactions, presence of other malignancies, active infection, and/or known HIV infection are ineligible to enroll. The study also excludes individuals who had received other investigational agents, chemotherapy, or who require systemic treatment with corticosteroids or other immunosuppressive therapy.

Recruitment for the FLAMINGO-01 study is pending at centers in California, New York, and Texas.

_REFERENCE:

_{1. Greenwich LifeSciences announces removal of clinical hold permitting phase III clinical trial to proceed. News release. Greenwich LifeSciences. July 12, 2022. Accessed July 13, 2022. https://bit.ly/3P772Ai}

_{2. 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.gov. Updated June 30, 2022. Accessed July 13, 2022. https://bit.ly/3IA1vQh}