海报库PosterKeep
PO.CT01.05 · 临床试验

评估GLSI-100（GP2 + GM-CSF）在新辅助及术后辅助抗HER2治疗后残留病灶或高风险pCR乳腺癌患者中疗效和安全性的进行中III期研究（Flamingo-01）开放标签组迟发型超敏免疫应答的初步结果

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

海报缩略图：评估GLSI-100（GP2 + GM-CSF）在新辅助及术后辅助抗HER2治疗后残留病灶或高风险pCR乳腺癌患者中疗效和安全性的进行中III期研究（Flamingo-01）开放标签组迟发型超敏免疫应答的初步结果
编号 CT138 展板 2 时间 4/20 02:00–05:00 区域 Section 52 主讲 Snehal Patel, MS
分会场 Phase II and Phase III Clinical Trials
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作者与单位 Authors & Affiliations

Snehal S. Patel1, Jaye Thompson1, F. Joseph Daugherty1, Francois-Clement Bidard2, William J. Gradishar3, Marcus Schmidt4, Miguel Martin5, Joyce A. O’Shaughnessy6, Hope S. Rugo7, Cesar A. Santa-Maria8, Laura M. Spring9, Mothaffar F. Rimawi10

1Greenwich LifeSciences, Stafford, TX,2Institut Curie, Paris, France,3Northwestern University, Chicago, IL,4University Medical Center Mainz, Mainz, Germany,5GEICAM, Madrid, Spain,6Sarah Cannon Research Institute, Dallas, TX,7City of Hope Comprehensive Cancer Center, Duarte, CA,8Johns Hopkins University, Baltimore, MD,9Massachusetts General Hospital, Boston, MA,10Lester and Sue Smith Breast Center, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX

摘要 Abstract

中文摘要
背景：本III期试验是一项在HLA-A*02患者中开展的前瞻性、随机、双盲、多中心研究（NCT05232916），在美国和欧洲约140个中心进行。目前一个约250例非HLA-A*02患者的第三个非随机组已完全入组，下文呈现初步免疫应答数据。GP2是HER2/neu蛋白的一种九氨基酸生物肽，与粒细胞-巨噬细胞集落刺激因子（GM-CSF）联合给药，刺激靶向表达HER2/neu癌症的免疫应答，该联合方案称为GLSI-100。 方法：在标准新辅助和辅助治疗后，将在前6个月内给予6次皮内注射GLSI-100，随后在接下来的2.5年内给予5次加强针。受试者试验持续时间为3年治疗加1年额外随访。使用迟发型超敏反应（DTH）皮肤试验和注射部位反应（ISRs）随时间测量对GP2的免疫应答。患者群体由以下关键入选标准界定：1）HER2/neu阳性及HLA，2）新辅助治疗后残留病灶或高风险pCR（就诊时III期），3）排除IV期，4）完成至少90%计划的基于trastuzumab的治疗。 结果：所有患者（n=247）均接种了GLSI-100并继续治疗和随访。使用DTH反应（红斑）评估患者的体内免疫应答。在注射后48-72小时测量DTH正交均值。在本初步数据分析中，第4个月或第6个月经历DTH反应的受试者百分比较基线有显著增加。DTH反应频率增加了约4倍，从基线（任何GLSI-100给药之前）时5.2%患者经历DTH反应，增加至第4个月或第6个月时20.4%患者经历DTH反应（McNemar检验，p<0.001）。研究正在进行中，数据收集和清理仍在继续，因此最终结果可能有所不同。 结论：本项GLSI-100治疗的非HLA-A*02患者初步分析中发现的DTH反应发生率随时间增加，表明GLSI-100治疗不应局限于HLA-A*02基因型。如本初步数据所证明，接受GLSI-100治疗的受试者越来越能够对GP2产生免疫应答。未来研究可探索利用免疫应答来评估：DTH与ISRs的相关性、GLSI-100按特定HLA类型的免疫原性、维持免疫的加强针时机、临床中心表现，以及对无应答者停止治疗。 资助：本试验由Greenwich LifeSciences支持。
查看英文原文 English 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.

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