ALLO-316

如果您对创新性细胞疗法感兴趣，请联系药时代BD团队（BD@drugtimes.cn）！ 全文共932字，共0图 预计阅读时间：4分钟 当地时间2025年8月1日，Allogene Therapeutics（以下简称为“Allogene”）宣布，其在研CD19通用型CAR-T——cemacabtagene ansegedleucel（cema-cel）的ALPHA3研究中出现一例患者死亡案例！ Allogene是通用型CAR-T领域的先驱，于2017年成立，总部位于美国加州南旧金山。通过核心技术平台AIIOCAR T™，目前Allogene已建立多条通用型CAR-T管线。cema-cel是其管线中进展最快的，已处于II期临床阶段。 此次出现患者死亡案例的试验，是Allogene正在进行的 II期ALPHA3研究。Allogene公告指出，死亡案例与cema-cel无关，主要由清淋方案中CFA（环磷酰胺+ALLO-647）的ALLO-647引起。具体来看，这起严重的不良反应数据发生在患者输注后的第54天，为由肝功能衰竭引起的死亡，推测是在免疫抑制状态下发生播散性腺病毒感染所致。 为应对，Allogene目前已全面停止涉及ALLO-647的研究臂，与FDA及安全监测委员会 （DSMB） 和指导委员会协商后，准备将清淋方案换回标准清淋方案，即环磷酰胺+氟达拉滨（FC）。并将临床试验改为常规的双臂研究，试验方案为：每组（FC 治疗组 vs 观察组）纳入 110 例 LBCL（大B细胞淋巴瘤）患者，这些患者在完成一线（1L）治疗后达到完全缓解（CR）或部分缓解（PR）状态，但存在微小残留病灶（MRD）。研究的主要终点为“基于盲态独立影像评估委员会（IRC）判定的无事件生存期（EFS）”。 目前，据Allogene披露，这项无效性分析将于2026年上半年公布。对于本例患者死亡案例，Allogene总裁、首席执行官兼联合创始人David Chang博士表示：这一事件促使我们提前审查试验数据，并做出了一个果断的决定——这一决定可能最终帮助这款潜在挽救生命的疗法更快惠及患者。采用标准FC淋巴清除方案后，在门诊环境中使用cema-cel的治疗方式将简化研究流程，有望加速试验入组并优化监管审查路径，从而为患者带来治疗模式的革新。” 经历患者死亡案例后，Allogene从战略上将ALPHA3试验的清淋方案该换为标准FC方案标志着Allogene临床策略的重大调整。此后，所有开放入组的试验及研发管线项目均不再使用ALLO-647。公司正转而通过专有Dagger®平台技术推进下一代AlloCAR T候选产品，该技术旨在减少甚至可能完全替代传统淋巴清除方案。这一策略已应用于治疗晚期肾细胞癌的ALLO-316 TRAVERSE试验和治疗自身免疫性疾病的ALLO-329 RESOLUTION试验，两者均利用Dagger®技术降低对传统淋巴清除方案的依赖。 参考资料： 1.公司官网 2.其他公开资料 图片来源：即梦AI 全球首例临床改善！中山三院联合士泽生物推进通用型iPSC再生神经细胞治疗脊髓损伤 2025-08-04 云顶新耀战略增持I-Mab，成为其第一大股东 2025-08-02 艾伯维放出豪言：明年将成为业内最大的CNS公司！ 2025-08-02 版权声明/免责声明 本文为原创文章。 本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。 文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。 如有任何问题，请与我们联系。 衷心感谢! 药时代官方网站:www.drugtimes.cn 联系方式: 电话:13651980212 微信:27674131 邮箱:contact@drugtimes.cn 点击这里，查看更多精彩！

Lymphodepletion Regimen Selection Made in Conjunction with the ALPHA3 Data and Safety Monitoring Board (DSMB) and Steering Committee, and in Consultation with the FDA Following an ALLO-647-Related Death in the FCA (FC plus ALLO-647) Lymphodepletion Arm Unplanned Review of Safety and Biomarker Data with Standard FC and Cema-cel Indicates Encouraging MRD Conversion Rate and Safety Profile ALPHA3 Study Now Proceeds as a Two-Arm Randomized Study Comparing Cema-cel After Standard FC Lymphodepletion to Observation; Scheduled Futility Analysis Remains 1H 2026, as Planned Conference Call and Webcast Scheduled for Today at 8:00 AM PT/11:00 AM ET Aug. 01, 2025 -- Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) products for cancer and autoimmune disease, today announced that it has selected standard fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen to be used in its ALPHA3 study evaluating cemacabtagene ansegedleucel (cema-cel) in first-line consolidation for large B-cell lymphoma (LBCL). This lymphodepletion regimen selection was made in conjunction with the ALPHA3 Data and Safety Monitoring Board (DSMB) and Steering Committee and following consultation with the U.S. Food and Drug Administration (FDA). The arm testing FC plus ALLO-647, an anti-CD52 mAb (FCA), is now closed to further enrollment. This decision, made ahead of the scheduled futility analysis, was prompted by a Grade 5 adverse event in the FC plus ALLO-647 arm that has been attributed to the use of ALLO-647. The event occurred on Day 54 post-infusion from hepatic failure, believed to have resulted from disseminated adenovirus infection in the setting of immune suppression. This event was deemed unrelated to cema-cel. Severe viral infections have been rare across Allogene’s clinical trials. However, when present, they have been attributed to immunosuppression due in part to ALLO-647. There have been no cases of adenoviral infection or hepatic failure in any participant treated with FC lymphodepletion across Allogene’s trials. “The loss of a patient is always deeply saddening, and we extend our heartfelt condolences to the patient’s family,” said David Chang, M.D., Ph.D., President, Chief Executive Officer, and Co-Founder of Allogene. “This event, which prompted an early review of the trial data, compelled us to make a decisive choice - one that may ultimately help bring this potentially life-saving therapy to patients more quickly. The ability to administer cema-cel following standard FC lymphodepletion in an outpatient setting will simplify study treatment and has the potential to accelerate trial enrollment and streamline regulatory review, ultimately transforming care for patients.” The adoption of standard FC in the ALPHA3 trial marks a key shift in Allogene’s clinical strategy. As a result, no trials open to enrollment or pipeline programs include ALLO-647. Instead, the Company is advancing its next-generation AlloCAR T product candidates using the proprietary Dagger® Platform Technology, which is designed to minimize or potentially eliminate the need for standard lymphodepletion. This approach is showcased in the ALLO-316 TRAVERSE trial for advanced renal cell carcinoma and the ALLO-329 RESOLUTION trial for autoimmune diseases, both of which leverage the Dagger® Technology to reduce reliance on traditional lymphodepletion strategies. The amended ALPHA3 trial now proceeds as a randomized study with two arms, comparing cema-cel after standard FC lymphodepletion to observation, the current standard of care. Statistical design of the trial and the prespecified study conduct remain the same. The next milestone will be the futility analysis comparing MRD conversion and is expected to occur 1H 2026. To date, over 50 clinical sites are activated across the United States and Canada, including community cancer centers and major academic institutions. Allogene will host a live conference call and webcast today at 8:00 a.m. PT / 11:00 a.m. ET to discuss this recent update. If you would like the option to ask a question on the conference call, please use this link to register. Upon registering for the conference call, you will receive a personal PIN to access the call, which will identify you as the participant and allow you the option to ask a question. The listen-only webcast will be made available on the Company's website at www.allogene.com under the Investors tab in the News and Events section. Cemacabtagene ansegedleucel, or cema-cel, is a next generation anti-CD19 AlloCAR T™ investigational product for the treatment of large B cell lymphoma (LBCL). The ALPHA3 pivotal Phase 2 trial in first line (1L) consolidation for the treatment of LBCL launched in June 2024. Allogene has oncology rights to cema-cel in the US, EU and UK with options for rights in China and Japan. Over 60,000 patients are expected to be treated for LBCL annually in the US, the EU and the UK. While first line (1L) R-CHOP or other chemoimmunotherapy is effective for most patients, approximately 30% who initially respond will relapse and require subsequent treatment. The current standard of care after 1L treatment has been simply to “watch and wait” to see if the disease relapses. The pivotal Phase 2 ALPHA3 study takes advantage of cema-cel as a one-time, “off-the-shelf” treatment that can be administered immediately upon discovery of MRD following six cycles of R-CHOP or other chemoimmunotherapy, positioning it to become the standard “7th cycle” of frontline treatment available to all eligible patients with MRD. Allogene Therapeutics, with headquarters in South San Francisco, is a clinical-stage biotechnology company pioneering the development of allogeneic chimeric antigen receptor T cell (AlloCAR T™) products for cancer and autoimmune disease. Led by a management team with significant experience in cell therapy, Allogene is developing a pipeline of “off-the-shelf” CAR T cell product candidates with the goal of delivering readily available cell therapy on-demand, more reliably, and at greater scale to more patients. The content above comes from the network. if any infringement, please contact us to modify.