Novel Immunotherapy Reduces Breast Recurrence Rates in Non-HLA-A*02 Population

A continued reduction in breast recurrence rate was noted in the non-HLA-A*02 arm of the phase 3 FLAMINGO-1 trial (NCT05232916) assessing GLSI-100, a novel immunotherapy, in patients with HER2/neu primary breast cancer, according to a press release from Greenwich LifeSciences.¹

Since the most recent update 6 months ago, the recurrence rate was less than 1% per year in patients with non-HLA-A*02 disease who were treated with GLSI-100, after the completion of the primary immunization series. A Kaplan-Meier curve is not possible for this arm of the analysis because there was no direct placebo comparator arm for the non-HLA-A*02 arm. After GLSI-100 administration, the majority of patients also received ado-trastuzumab emtansine (TDM-1; Kadcyla).

After the data cutoff, the recurrence rate in patients treated with GLSI-100 in the non-HLA-A*02 arm after completion of the primary immunization series over an average of 1.2 years of patient exposure remained significantly smaller than the 4% annual recurrence rate observed in the phase 3 KATHERINE study (NCT01772472), which assessed T-DM1 over a similar time period. The annual recurrence rate was 0.7% vs 4%, with an 83% reduction in recurrence rate and Chi Square (P <.0005).

The primary immunization series has been completed in virtually all patients in the non-HLA-A*02 arm, which includes the first 6 monthly vaccinations in the study. In the non-HLA-A*02 patient database, approximately 110 patient-years are added every 6 months.

Future updates may be presented at upcoming medical conferences.

In the overall FLAMINGO-1 trial, over 1000 patients have been screened, with that amounting to a current screen rate of approximately 800 patients per year. In the non-HLA-A*02 arm, 250 patients have been fully enrolled, and all have received GLSI-100. The primary immunization series includes the first 6 GLSI-100 injections over the first 6 months. This is required for peak protection and followed by 5 booster injections that are given every 6 months to help prolong immune response, leading to longer-term protection.

Of note, after 5 years of follow-up, there was an 80% or greater reduction in cancer recurrence in patients who were HER2/neu 3+ and treated with GLSI-100. These patients were disease-free over the first 6 months. Investigators believe 6 months is the time period required to reach peak immunity for maximum efficacy and protection.

The primary end point of the trial was invasive breast cancer-free survival.² Secondary end points included invasive disease-free survival, distant disease-free survival, and overall survival. Other pre-specified end points included immune response measurements.

GLSI-100 was administered to those in the HLA-A*02 and non-HLA-A*02 arms intradermally every month for the first 6 months, followed by every 6 months for the next 2.5 years, which equated to 11 intradermal injections over 3 years.

Patients were included in treatment if they were HLA-A*02–positive unless enrolled on the non-HLA-A*02 arm, had histologically confirmed HER2/neu positive primary breast cancer for all tumors biopsied, completed neoadjuvant and adjuvant trastuzumab-based treatment, had stage I to III disease at presentation with pathologic evidence of residual invasive carcinoma in the breast or axillary nodes, and had no clinical evidence of residual or persistent breast cancer per treating physician assessment.

Patients were excluded from treatment if they had stage IV cancer or metastatic breast cancer at any time, inflammatory breast cancer, receipt of other investigational agents, receipt of chemotherapy, or required long-term systemic treatment with corticosteroids or other immunosuppressive therapy.

In September 2025, GLSI-100 was given fast track designation by the FDA for patients with HER2-positive breast cancer who are HLA-A*02-positive and have completed standard-of-care HER2-targeted therapy to improve invasive breast cancer-free survival.³

References

1. Greenwich LifeSciences provides update showing continued reduction in recurrence rate in the open label arm of FLAMINGO-01. News release. Greenwich LifeSciences. March 17, 2026. Accessed March 17, 2026. https://tinyurl.com/372js77p
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 October 3, 2025. Accessed March 17, 2026. https://tinyurl.com/3fdjv2us
3. Greenwich LifeSciences’ GLSI-100 granted US FDA fast track designation. News release. September 10, 2025. Accessed March 17, 2026. https://tinyurl.com/2c5yzhcc