FDA Grants Fast Track Designation to GLSI-100 in HLA-A*02+, HER2+ Breast Cancer

The FDA has granted fast track designation to GLSI-100 for the treatment of patients with HLA-A*02-positive, HER2-positive breast cancer who have completed treatment with standard-of-care HER2-targeted therapy to improve invasive breast cancer–free survival.1

The agent is currently under evaluation in the phase 3 FLAMINGO-01 trial (NCT05232916) in patients with HLA-A*02-positive, HER2-positive breast cancer.2

“Greenwich is pleased that the FDA sees the potential of GLSI-100 to change important clinical outcomes in this population of breast cancer patients.1 We continue to work earnestly to collect data to support a biologics license application filing demonstrating this benefit,” Jaye Thompson, PhD, vice president of Clinical and Regulatory Affairs at Greenwich LifeSciences, stated in a news release.

What Is GLSI-100, and What Prior Data Support the Ongoing Phase 3 FLAMINGO-01 Trial?

GP2 is a biologic 9-amino acid peptide of the HER2 protein given in combination with granulocyte macrophage colony–stimulating factor (GM-CSF), an FDA-approved immunoadjuvant, to elicit an immune response against HER2-expressing cancers.2

Interim data from the prior phase 2b trial (NCT00524277) demonstrated that the addition of GP2 to GM-CSF (GLSI-100; n = 89) led to an estimated 5-year disease-free survival (DFS) rate of 88% (95% CI, 78%-94%) vs 81% (95% CI, 69%-89%) with GM-CFS alone (n = 91; P = 0.43) in patients with clinically disease-free, node-positive, high-risk node-negative, HLA-A*02-positive, HER2-positive breast cancer.3

At the time of the analysis, the median follow-up was 34 months (range, 1-60). Although the study was deemed negative, results suggested there may have been heightened activity in patients with HER2 overexpression who received the full vaccine series. In this population, the estimated 5-year DFS rate was 100% in vaccinated patients (n = 48) vs 89% (95% CI, 71%-96%) in control patients (n = 50; P = .08).

What Is the Design of the FLAMINGO-01 Trial?

The ongoing FLAMINO-01 trial is a prospective, randomized, double-blinded, multicenter study designed to assess whether extended adjuvant therapy with GLSI-100 can improve invasive breast cancer–free survival in patients with HER2-positive breast cancer following surgery and 12 months of adjuvant trastuzumab (Herceptin)–based therapy.2

Eligible patients must have HLA-A*02-positive, HER2-positive breast cancer with residual disease after (neo)adjuvant therapy and surgery. Documented pathologic complete response must be present if the patient had stage III disease at presentation.

Patients will be randomly assigned to receive treatment with GLSI-100 or a saline placebo.

At the end of trastuzumab-based therapy, patients will receive 6 intradermal injections of GLSI-100 or saline placebo during the first 6 months followed by 5 boosters over the next 2.5 years, amounting to 11 total injections over a 3-year period. Following treatment, patients will be subject to 1 year of follow-up.

The primary objective of the study is invasive breast cancer–free survival. Secondary end points include invasive DFS, distant DFS, overall survival, and quality of life assessments. In vitro and in vivo immunologic responses to therapy will also be evaluated to understand the association between responses and clinical outcomes.

Approximately 498 patients will be enrolled. Per the study design, 28 events will need to occur to detect a hazard ratio of 0.3 in invasive DFS. An interim analysis for superiority and futility will be performed when at least 14 of these events have happened. With this sample size, the study will have 80% power if the annual event rate in the control arm is at least 2.4%.

How Will the Fast Track Designation Affect the Development of GLSI-100?

“We are excited to have received fast track designation,” Snehal S. Patel, MBA, chief executive officer of Greenwich LifeSciences, added in the news release.1 “The FDA review of our fast track application included a review of the potential of GLSI-100 as a new drug to treat serious conditions and to fill unmet medical need. By showing the potential of GLSI-100 to prevent metastatic breast cancer recurrence in the patient population that we are studying, we were able to estimate the potential lives that could be saved. The company plans to continue discussions with the FDA, and potentially the European regulatory authorities, to explore additional ways to make GP2 and GLSI-100 available to larger populations.”

References

1. Greenwich LifeSciences’ GLSI-100 granted US FDA fast track designation. News release. Greenwich LifeSciences, Inc. September 10, 2025. Accessed September 10, 2025. https://investor.greenwichlifesciences.com/news-events/press-releases/detail/102/us-fda-fast-track-designation
2. Patel S, Thompson J, Patel M, et al. 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 both neo-adjuvant and postoperative adjuvant anti-HER2 therapy: Flamingo-01. J Clin Oncol. 2025;43(suppl 16):TPS618. doi:10.1200/JCO.2025.43.16_suppl.TPS618
3. Mittendorf EA, Ardavanis A, Litton JK, et al. Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide GP2 vaccine in breast cancer patients to prevent recurrence. Oncotarget. 2016;7(40):66192-66201. doi:10.18632/oncotarget.11751