Treatment with the novel immunotherapy GLSI-100 led to a low recurrence rate in patients with HER2-positive breast cancer who had residual disease or a high-risk pathologic complete response (pCR) at surgery and who have completed both neoadjuvant and postoperative adjuvant trastuzumab (Herceptin)-based treatment, according to data from the open-label portion of the ongoing phase 3 FLAMINGO-01 trial (NCT05232916).
Notably, the open-label arm of the study includes patients with HLA-A*02–negative disease; the randomized, double-blinded portion of the trial is evaluating GLSI-100 vs placebo in patients with HLA-A*02–positive disease.
Results from the open-label cohort (n = 250) announced by Greenwich LifeSciences showed that the recurrence rate was less than 1% per year following the completion of the primary immunization series (PIS).
Although the open-label arm of FLAMINGO-01 does not have a comparator arm, Greenwich LifeSciences offered a comparison with previously reported data from the phase 3 KATHERINE trial (NCT01772472), which supported the May 2019 FDA approval of ado-trastuzumab emtansine (T-DM1; Kadcyla) for the adjuvant treatment of patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.2
The less than 1% recurrence rate reported with GLSI-100 reported following the completion of PIS over an average of 1.2 years of patient exposure was statistically significant compared with the 4% annual recurrence rate over 1.2 patient years with T-DM1 in the KATHERINE trial.1
Additionally, data for immune response at baseline prior to exposure to GLSI-100, increased immune response during PIS, and the safety profile of the agent trended similarly to findings for HLA-A*02–positive patients treated in FLAMINOGO-01 and a prior phase 2b trial (NCT00524277).
Although preliminary data from the open-label portion of FLAMINGO-01 have read out, the study remains blinded.
In September 2025, the FDA 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 (IBCFS).3
Open-Label, Phase 3 Data for GLSI-100 in HER2+ Breast Cancer
- GLSI-100 led to low recurrence rates in patients with HLA-A*02–negative, HER2-positive breast cancer who had residual disease or a high-risk pCR following perioperative trastuzumab-based therapy.
- The less than 1% recurrence rate compared favorably with the recurrence rates reported in the KATHERINE study, which supported the May 2019 FDA approval of adjuvant T-DM1 for patients with HER2-positive breast cancer who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment.
- The double-blinded portion of FLAMINGO-01 is ongoing, where patients with HLA-A*02–positive disease are being randomly assigned to receive GLSI-100 or placebo.
How is the FLAMINGO-01 trial designed?
FLAMINGO-01 is a prospective, randomized, double-blinded, placebo-controlled, multicenter, phase 3 trial enrolling patients with histologically confirmed HER2-positive breast cancer who completed standard-of-care neoadjuvant and adjuvant trastuzumab-based therapy.4 Patients need to have stage I to III disease with pathological evidence of residual disease in the breast or axillary lymph nodes at surgery following neoadjuvant therapy; or stage III disease with a pCR at surgery following neoadjuvant therapy.
Other key inclusion criteria comprise an ECOG performance status of 0 to 2 and adequate organ function. Patients cannot have clinical evidence of residual or persistent breast cancer. The study is also excluding patients with stage IV disease at any time and those with inflammatory breast cancer.
In the blinded portion of the study, patients with HLA-A*02–positive disease are being randomly assigned to receive GLSI-100 at 500 µg/mL plus granulocyte-macrophage colony-stimulating factor (GM-CSF) at 125 µg/mL; or placebo once per month for the first 5 months, then once every 6 months for the next 2.5 years, totaling 11 injections over 3 years. HLA-A*02–negative patients included in the open-label arm received GLSI-100 plus GM-CSF at the same dose levels and frequency as the blinded experimental arm.
IBCFS is serving as the trial’s primary end point. Secondary end points include invasive disease-free survival, disease disease-free survival, overall survival, and quality of life. Immune response outcomes are also being measured.
Approximately 500 patients will be randomly assigned between the blinded GLSI-100 and placebo arms.1 The study is powered to detect a HR of 0.3 for IBCFS, with 28 events required to trigger the analysis. An interim analysis for superiority and futility will also be conducted at 14 IBCFS events.
References
- 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://investor.greenwichlifesciences.com/news-events/press-releases/detail/117/open-label-arm-of-flamingo-01
- FDA approves ado-trastuzumab emtansine for early breast cancer. FDA. Updated May 6, 2019. Accessed March 17, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ado-trastuzumab-emtansine-early-breast-cancer
- Greenwich LifeSciences’ GLSI-100 granted US FDA fast track designation. News release. Greenwich LifeScience. September 10, 2025. Accessed March 17, 2026. https://investor.greenwichlifesciences.com/news-events/press-releases/detail/102/us-fda-fast-track-designation
- 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://clinicaltrials.gov/study/NCT05232916
