PO.CT01.05 · 临床试验
Preliminary delayed-type-hypersensitivity immune response results from open-label arm of on-going 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
作者与单位
摘要 Abstract
Background : This Phase III trial is a prospective, randomized, double-blinded, multi-center study ( NCT05232916 ) in HLA-A*02 patients at approximately 140 sites in the US and Europe. A third non-randomized arm of approximately 250 non-HLA-A*02 patients is now fully enrolled and preliminary immune response data is presented below. GP2 is a biologic nine amino acid peptide of the HER2/ neu protein delivered in combination with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) that stimulates an immune response targeting HER2/neu expressing cancers, the combination known as GLSI-100.
Methods : After standard of care neoadjuvant and adjuvant therapy, 6 intradermal injections of GLSI-100 will be administered over the first 6 months and 5 subsequent boosters will be administered over the next 2.5 years. The participant duration of the trial will be 3 years treatment plus 1 additional year follow-up. Immune responses to GP2 were measured over time using delayed-type-hypersensitivity (DTH) skin tests and injection site reactions (ISRs). The patient population is defined by these key eligibility criteria: 1) HER2/neu positive and HLA, 2) Residual disease or High risk pCR (Stage III at presentation) post neo-adjuvant therapy, 3) Exclude Stage IV, and 4) Completed at least 90% of planned trastuzumab-based therapy.
Results : All patients (n=247) were vaccinated with GLSI-100 and continue in treatment and follow-up. A DTH reaction (redness) was used to assess in vivo immune responses in patients. The DTH orthogonal mean was measured 48-72 hours after injection. In this preliminary data analysis, there was a significant increase in percentage of subjects experiencing a DTH reaction in month 4 or month 6 compared to baseline. The frequency of DTH reactions increased by approximately 4x from 5.2% of the patients experiencing a DTH reaction at baseline, prior to any GLSI-100 administration, to 20.4% of the patients experiencing a DTH reaction in month 4 or month 6 (McNemar, p < 0.001). The study is ongoing and data collection and cleaning continue so final results may vary.
Conclusions : The increase in the incidence of DTH reactions over time found in this preliminary analysis of GLSI-100 treated non-HLA-A*02 patients shows that GLSI-100 treatment should not be limited to the HLA-A*02 genotype. Subjects treated with GLSI-100 were increasingly able to mount an immune response to GP2 as evidenced in this preliminary data. Future investigations may explore the use of immune responses to assess: correlation of DTH to ISRs, immunogenicity of GLSI-100 by specific HLA type, timing of boosters to sustain immunity, clinical site performance, and the discontinuation of treatment for non-responders.
Funding : This trial is supported by Greenwich LifeSciences.
利益披露 Disclosure
S. S. Patel,
Greenwich LifeSciences Employment, Stock, Stock Option.
J. Thompson,
Greenwich LifeSciences Employment, Stock, Stock Option.
F. Daugherty,
Greenwich LifeSciences Independent Contractor, Stock, Stock Option.
F. Bidard,
Greenwich LifeSciences ).
GE Healthcare, Menarini Silicon Biosystems, Merck KGaA, MSD, Natera, Novartis, Personalis, Pfizer, Prolynx, Roche, SAGA Dx, Tempus ).
AstraZeneca, Daiichi-Sankyo, Lilly, Novartis, Pfizer, Roche Travel.
AstraZeneca, Daiichi-Sankyo, Lilly, Novartis, Roche Speaker.
AstraZeneca, Carrick, Daiichi-Sankyo, Hengrui, Inatherys, Lilly, Menarini Silicon Biosystems, Novartis, Pfizer, Relay Tx, Roche, Tempus Other, Advisory Boards.
W. J. Gradishar,
Greenwich LifeSciences ).
Genentech/Roche Other, IDMC.
AstraZeneca Other, IDMC.
Exact Sciences Other, Consulting/Advisory Board.
Pfizer Other, Consulting/Advisory Board.
Eli Lilly Other, Consulting/Advisory Board.
Menarini/Stemline Other, Consulting/Advisory Board.
Celcuity Other, Consulting/Advisory Board.
Arvinas Other, Consulting/Advisory Board.
Esai Other, Consulting/Advisory Board.
M. Schmidt,
AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Eurobio, Exact Sciences, Gilead, Lilly, Menarini-Stemline, Molecular Health, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche Other, Personal fees.
straZeneca, BioNTech, Eisai, Genentech, the German Breast Group, Novartis, Palleos, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche ).
Patents EP 2390370 B1 and EP 2951317 B1 Other, Inventor on patents EP 2390370 B1 and EP 2951317 B1.
M. Martin,
Greenwich LifeSciences Other, Consultant/Advisor.
Roche, PUMA and Novartis ).
AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology, Daiichi Sankyo and Pfizer Other, consulting/advisory fees.
AstraZeneca, Lilly, Amgen, Roche/Genentech, Novartis, and Pfizer Other, speakers’ honoraria.
J. A. O’Shaughnessy,
Greenwich LifeSciences Other, Honoraria.
Agendia Other, Honoraria.
Amgen Biotechnology Other, Honoraria.
AstraZeneca Other, Honoraria.
Bristol Myers Squibb Other, Honoraria.
Daiichi Sankyo Other, Honoraria.
Eisai Other, Honoraria.
G1 Therapeutics Other, Honoraria.
Genentech Other, Honoraria.
Gilead Sciences Other, Honoraria.
Eli Lilly Other, Honoraria.
Merck Other, Honoraria.
Novartis Other, Honoraria.
Pfizer Other, Honoraria.
Pierre Fabre Pharmaceuticals Other, Honoraria.
Puma Biotechnology Other, Honoraria.
Roche Other, Honoraria.
Sanofi Other, Honoraria.
Seagen Other, Honoraria.
Mersana; Stemline-Menarini; Jazz Pharmaceuticals; Summitt; BioNTech; Ellipses; TerSera Therapeutics; J&J; Duality; Natera; Guardant; Tempus; Exact Sciences; Hibercell; AADI Bioscience Other, Honoraria.
H. S. Rugo,
Greenwich LifeSciences ), Other.
Napo, Bristol Myers Squibb, Helsinn, and BioNTech Other, Consulting or advisory role.
AstraZeneca, Gilead Sciences, Inc., Lilly, Merck & Co., Daiichi Sankyo, Inc., Novartis Pharmaceuticals, Pfizer Other, Institutional research funding.
F. Hoffman-La Roche/Genentech, Stemline Therapeutics, and Ambryx; and institutional research funding to City of Hope from Bicycle Therapeutics, F. Hoffman-La Roche/Genentech Other, Institutional research funding.
Merck & Co.; Stemline Therapeutics Other, Institutional research funding.
C. A. Santa-Maria,
Greenwich LifeSciences ).
Merck, BMS, Pfizer, Astazeneca/Daiichi ,Celldex, Bicycle Therapeutics, Genetech, Greenwich Life Sciences, Gilead ).
Immunomic Therapeutics, Astrazeneca, Daiichi, Natera Other, Consulting.
L. M. Spring,
Novartis; Daiichi Pharma; Astra Zeneca; Eli Lilly; Precede; Seagen; Pfizer; Gilead Other, Consultant/advisory board.
Merck; Genentech; Gilead; Eli Lilly; Astra Zeneca; Greenwich LifeSciences ).
M. Rimawi,
Daiichi Sankyo Other, Consulting/Honorarium.
AstraZeneca Other, Consulting/Honorarium.
Genentech Other, Consulting/Honorarium.
Novartis Other, Consulting/Honorarium.
Pfizer Other, Consulting/Honorarium.
Greenwich LifeSciences ).
Tempus Other, Consulting/Honorarium.
Stemline Other, Consulting/Honorarium.
Gilead Other, Consulting/Honorarium.