The Ongoing Investigation of GLSI-100 Continues in the Flamingo-01 Study for HER2/Neu+ Breast Cancer

Greenwich LifeSciences, Inc, the manufacturer of the immunotherapy GLSI-100, announced several updates regarding the phase 3 Flamingo-01 trial (NCT05232916), which is evaluating the HER2/neu peptide agent in patients with HER2/neu-positive primary breast cancer, according to information from a press release.¹

GLSI-100 is comprised of the biologic 9 amino acid peptide of the HER2/neu protein GP2 in combination with the FDA-approved granulocyte-macrophage colony stimulating factor (GM-CSF) sargramostim (Leukine) which stimulates an immune response directed towards HER2/neu-expressing cancers. Flamingo-01 is evaluating the use of GLSI-100 as an extended adjuvant therapy to prolong invasive disease-free survival (iDFS) in patients with HER2/neu-positive breast cancer following surgery and after the first year of treatment with any trastuzumab (Herceptin)–based therapy.²

The press release announced that the Flamingo-01 trial Data Safety Monitoring Board, which met twice in 2023, has recommended to continue the study as is without modification. No serious adverse effects (AEs) related to GLSI-100 have been reported to date.¹

Additionally, during both the 2023 San Antonio Breast Cancer Symposium and the 2023 ASCO Annual Meeting, the manufacturer of GLSI-100 met with the Flamingo-01 Steering Committee, clinicians from the United States and Europe who are participating in the study. The Steering Committee discussed unpublished findings which suggest that GP2 may bind to various HLA types and not just HLA-A*02, as well as prior data supporting a planned third arm of Flamingo-01, which was expected to enroll 100 non-HLA-A*02 patients. However, based on this updated data, this number will be expanded to 250 patients.

"Among my peers, the level of interest in the Flamingo-01 trial is very high,” Mothaffar F. Rimawi, MD, said in the press release. “The new sites in Europe will make significant contributions to the trial in terms of patient enrollment as well as overall conduct of the trial. The expansion of the unblinded non-HLA-A*02 arm is also significant as it reflects the interest among patients and investigators in exploring the activity of GLSI-100 in these patients, which may expand the patient population who could benefit from this exciting vaccine."

Rimawi is the chair of the Flamingo-01 Steering Committee; the Dan L. Duncan Professor in the Department of Medicine, Section of Hematology and Oncology; executive medical director; and associate director of clinical affairs, the Dan L Duncan Comprehensive Cancer Center, at Baylor College of Medicine, in Houston, Texas.

Flamingo-01 is prospective, randomized, double-blinded, placebo-controlled, multicenter study investigating the use of GLSI-100 in patients withHLA-A*02- and HER2/neu-positive breast cancer who are at high risk for disease recurrence; these patients will have received both neoadjuvant and postoperative adjuvant standard of care therapy. Eligible patients must have an ECOG performance status of 2 or less; adequate organ function; no clinical evidence of residual or persistent breast cancer; stage I, II, or III disease at presentation; and be able to begin study therapy within one year of completion of adjuvant trastuzumab-based therapy and any other standard therapies. Notably, the administration of study therapy concurrently with endocrine therapy is permitted.³

Once enrolled, patients in the investigational and open-label arms will receive GLSI-100, which consists of GP2 500 mcg/mL and GM-CSF 125 mcg/mL, intradermally every month for first 6 months followed by treatment every 6 months for next 2.5 years for a total of 11 intradermal injections over 3 years. In the control arm, patients will receive 0.9% normal saline placebo at the same dosing schedule.

The primary end point is iDFS. Secondary end points include distant disease-free survival, overall survival, and patient quality of life.

The study will enroll approximately 500 patients with HLA-A*02 and 250 patients with other HLA types will receive GLSI-100 in the third arm. The study has been designed to detect a hazard ratio of 0.3 in invasive breast cancer-free survival, where 28 events will be required. An interim analysis for superiority and futility will be conducted when at least half of those events occur. The sample size provides 80% power if the annual rate of events in placebo-treated patients is at least 2.4%.¹

Previously, findings from the phase 2b study portion of the study evaluating GLSI-100 were completed in 2018. The study demonstrated that no recurrences were reported in patients with HER2/neu-positive breast cancer in the adjuvant setting following a median follow-up of 5 years if patients with HLA-A*02 were treated, followed, and remained disease-free over the first 6 months, which is the time needed to achieve peak immunity (P = .0338). Additionally, treatment with GLSI-100 led to a potent immune response per local skin tests and immunological assays. Among 146 patients treated with GLSI-100 across 4 clinical trials, the agent has been well tolerated and no serious AEs have been reported.²

Flamingo-01 has approximately 30 clinical sites across 87 locations, including the largest oncology network, in the United States. In Europe, pending expected regulatory approval in 2024, this number is expected to expand to an additional 105 to 120 sites, including in Spain, France, Germany, Italy, and Poland.

"With the addition of the European sites and approximately 150 total sites, peak enrollment rates could be reached by the end of 2024 allowing for a refinement in the interim analysis,” Snehal S. Patel, chief executive officer and board member of Green LifeSciences, said in the press release. “Currently, enrollment will likely end before the interim analysis is triggered by 14 events. However, the interim analysis could be modified such that an additional sizing interim analysis is conducted before enrollment ends to reaffirm the size of the 2 randomized arms. While the hazard ratio of 0.3 assumes that the recurrence rate of the treated arm will be 30% of the recurrence rate in the placebo arm and thus a 70% reduction in recurrence rate, and while the phase II trial showed even greater reduction in recurrence rate, we are likely to see recurrences in the treated arm of the Phase III trial and have designed the trial accordingly. Using the early phase III trial data to reaffirm the size of the arms of the phase III trial may be the best information we could use to reduce risk and improve the chances of success of Flamingo-01."

References

1. Greenwich LifeSciences Provides Update on Phase III Clinical Trial, Flamingo-01. News release. Greenwich LifeSciences, Inc. February 14, 2024. Accessed February 14, 2024. https://investor.greenwichlifesciences.com/news-events/press-releases/detail/77/phase-iii-clinical-trial-flamingo-01
2. Patel SS, Thompson J, Patel ME, 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 neoadjuvant and postoperative adjuvant anti-HER2 therapy: Flamingo-01. J Clin Oncol. 2023;41(suppl 16):TPS617. doi:10.1200/JCO.2023.41.16_suppl.TPS617
3. 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 January 16, 2024. Accessed February 14, 2024. https://www.clinicaltrials.gov/study/NCT05232916