CD70/CD19 CAR T(Allogene Therapeutics)

“We continue to believe cema-cel has the potential to leapfrog other autologous and allogeneic CD19 CAR-T therapies, remain competitive for longer, and expand the total addressable market,” William Blair analysts said.\n Two months after Allogene abandoned plans for its CAR-T in leukemia, analysts have suggested that fresh phase 1 data in lymphoma show the therapy can “leapfrog” the competition.The biotech had been studying the CD19 CAR-T cell therapy, called cemacabtagene ansegedleucel or cema-cel, in the phase 1 ALPHA and ALPHA2 studies of 87 heavily pretreated patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL).The updated data showed a combined overall response rate (ORR) and complete response (CR) rate that was “consistent with those observed with approved autologous CD19 CAR-T cell products for patients with R/R LBCL after two or more lines of systemic therapy,” Allogene said in a Feb. 13 post-market release.The treatment regimen that Allogene has already taken into the ALPHA3 phase 2 study of cema-cel showed the highest ORR and CR rates, of 67% and 58%, respectively, the company said.But it was the durability data that caught analysts’ attention. Patients who achieved a CR had “excellent outcomes,” according to Allogene, with a progression-free survival of 24 months and a median overall survival (OS) not reached. The median durability of response among patients receiving the phase 2 regimen was 23.1 months and the median OS for this cohort was not reached, the biotech said.“We continue to believe cema-cel has the potential to leapfrog other autologous and allogeneic CD19 CAR-T therapies, remain competitive for longer and expand the total addressable market,” William Blair analysts said in a Feb. 14 note.They also highlighted that all of the six patients with a low tumor burden had achieved a complete response. “Although we think this data point supports cema-cel’s potential as a therapeutic option in patients with minimum residual disease and its ongoing development in a frontline remission consolidation setting, we highlight the publication does not specify if any of the six patients were treated with the selected phase 2 regimen,” the analysts added.Allogene noted in its release that today’s results “represent the largest dataset of LBCL patients treated with an allogeneic CAR-T product and, with a minimum of two years of follow-up, the longest follow-up to date.”“With multiple patients in ongoing complete remissions beyond four years, the lingering question of whether an allogeneic CAR-T could deliver durable responses has now been answered,” Allogene Chief Medical Officer Zachary Roberts, M.D., Ph.D., said in the release.“Furthermore, these results provide potent evidence supporting the use of CAR-T in patients with low disease burden and the unique opportunity for the ALPHA3 trial to achieve something novel in this disease—predict and intervene before relapse,” Roberts added. “Opportunities to redefine the standard of care in oncology are rare, but if successful, ALPHA3 has the potential to achieve precisely that.”Last November, Allogene ended work on cema-cel in leukemia in the face of competition from the likes of Bristol Myers Squibb’s Breyanzi.Allogene’s pipeline also includes a CD70-targeting CAR-T called ALLO-316 that recently showed success in a phase 1 renal cell carcinoma trial as well as a CD19/CD70 dual CAR-T called ALLO-329 in preclinical development for autoimmune disease.

▎药明康德内容团队编辑 本期看点 1. 靶向TROP2的抗体偶联药物（ADC）OQY-3258在1期临床试验中表现亮眼，在初治三阴性乳腺癌患者中达到100%疾病控制率（DCR）。 2. 潜在“first-in-class”β连环蛋白多肽拮抗剂ST316在1期临床试验中获得作用机制验证。 3. 双功能性抗体疗法ficerafusp alfa与PD-1抑制剂pembrolizumab联用，在治疗二线及以上鳞状细胞肛管癌（SCAC）患者的1/1b期临床试验中，达到25.0%的确认客观缓解率（ORR）。 药明康德内容团队整理 ST316：公布1期临床试验数据 Sapience Therapeutics公司汇报了在研潜在“first-in-class”β连环蛋白（catenin）多肽拮抗剂ST316的1期临床试验安全性和生物标志物数据。ST316通过破坏β连环蛋白与BCL9的相互作用，抑制Wnt/β-连环蛋白信号通路。 数据显示，在所有测试剂量下，ST316均表现出良好的安全性和耐受性。接受ST316单药治疗的患者中所观察到的长期疾病稳定（SD）与ST316早期抗肿瘤活性信号相一致。接受治疗后，在7例接受评估的患者中，有4例显示β连环蛋白从细胞核转移至细胞质/膜，表明ST316能够进入肿瘤组织并成功与靶点结合。在1期试验中，ST316显著降低了患者的免疫抑制细胞表达，显示出潜在的免疫调节效应。 ETH47：公布1期临床试验顶线结果 Ethris公司宣布，其主打mRNA候选药物ETH47，在健康受试者中的进行的1期临床试验中获得积极的顶线数据。 ETH47旨在靶向哮喘急性加重的上游触发因素，它编码的干扰素λ（IFNλ）是一种在呼吸道抗病毒免疫中起关键作用的蛋白。本次试验数据显示，ETH47在鼻腔衬液中剂量依赖性诱导了IFNλ的产生，并且显著激活鼻拭子样本中抗病毒干扰素刺激基因mRNA的表达。 安全性方面，ETH47在所有剂量水平上均表现出良好的安全性和耐受性。无严重或重度不良事件，也无因不良事件导致的试验中断。未检测到mRNA、IFNλ蛋白或专有脂类化合物的全身性吸收，这有效降低了脱靶效应的风险。 OQY-3258：1期临床试验结果公布 Vincerx Pharma和Oqory公司公布了在研抗体偶联药物OQY-3258用于治疗实体瘤患者的1a/1b期临床试验结果。OQY-3258又名ESG401，是一款靶向TROP2的抗体偶联药物。截至2024年8月，约150名实体瘤患者入组这一临床试验，在多种乳腺癌亚型患者中观察到可喜结果。 在初治三阴性乳腺癌患者中（n=25），确认ORR为76%，疾病控制率为100%，中位缓解持续时间（DOR）和无进展生存期（PFS）尚未达到。截至2025年1月的最新数据显示确认ORR提高到80%。在HR阳性/HER2阴性乳腺癌患者中，确认ORR为39%，DCR为78%。中位PFS为7.4个月。 Ficerafusp alfa（BCA101）：公布1/1b期临床试验数据 Bicara Therapeutics公司公布了在研双功能性抗体疗法ficerafusp alfa与PD-1抑制剂pembrolizumab联用，治疗二线及以上鳞状细胞肛管癌患者的1/1b期临床试验的扩展队列试验数据。 截至2024年12月5日，确认的ORR为25.0%（7/28例），其中包括6例部分缓解（PR）和1例完全缓解（CR）。此外，还有1例患者正在等待确认PR。中位PFS为2.9个月，在可评估的27例患者中，12个月的无进展生存率为40.7%。 SAB-142：1期临床试验结果公布 SAB BIO公司公布了在研人类抗胸腺细胞免疫球蛋白疗法SAB-142在健康志愿者中进行的1期临床试验的积极顶线结果。这一研究达到安全性和药代动力学活性的主要终点，支持SAB-142进入2b期临床开发阶段，用于治疗1型糖尿病。 1期临床试验数据显示，SAB-142表现出良好的安全性特征，支持长期给药。并且生物标志物研究显示SAB-142表现出持久的免疫调节作用。SAB-142是一种人类多克隆免疫球蛋白，可针对多种杀伤胰岛β细胞的免疫细胞，调节它们的活性，从而起到保护胰岛β细胞的作用。 TX45：公布1b期临床试验数据 Tectonic Therapeutic宣布，其主打候选药物TX45在1b期急性血流动力学临床试验中取得积极中期数据。在患有2型肺动脉高压合并射血分数保留型心力衰竭（PH-HFpEF）的患者中，单次静脉输注TX45可显著改善左心室功能和肺部血流动力学。 在整个研究人群中，TX45使肺毛细血管楔压（PCWP）降低17.9%，PCWP已被证明与患者的运动耐受、发病率和死亡率相关。在合并毛细血管前肺动脉高压和毛细血管后肺动脉高压（CpcPH），且患者肺血管阻力（PVR）升高的患者亚组中，TX45使PVR降低超过30%，这一指标同PCWP一样，与患者的运动耐受及生存预后密切相关。 TX45是一款长效Fc-款松弛素（relaxin）融合蛋白。它的独特作用机制不仅改善肺部血流动力学，还能增强左心室功能。现有的肺动脉高压药物主要为肺血管扩张剂，尚未在PH-HFpEF患者中显示对左心室功能的改善。Tectonic Therapeutic官网表示，TX45具有成为“best-in-class”疗法的潜力。 CELZ-201-DDT：公布1/2期临床试验初步数据 Creative Medical Technology Holdings公司宣布，其基于干细胞的创新疗法CELZ-201-DDT，在治疗退行性椎间盘疾病（DDD）导致的慢性背痛的1/2期临床试验中取得积极的初步数据。首批患者共10例患者中8例接受CELZ-201-DDT的治疗，2例接受安慰剂治疗。 安全性数据显示：未发生剂量限制性毒性，无严重不良事件。盲态数据分析显示，CELZ-201-DDT在缓解背痛和恢复功能方面表现出可喜的治疗潜力。在对首批数据进行全面安全性评估后，独立数据安全监测委员会（DSMB）建议按计划推进临床试验至下一患者队列。 CELZ-201-DDT是Creative Medical Technology Holdings研发的基于干细胞的治疗产品，旨在修复受损椎间盘组织、减轻慢性背痛并恢复患者功能。 ALLO-329：IND申请获FDA许可 Allogene Therapeutics公司宣布，在研同种异体CAR-T细胞疗法ALLO-329用于治疗多种自身免疫性疾病的1期临床篮子试验的IND申请已经获得美国FDA的许可。这项名为RESOLUTION的1期篮子试验将在系统性红斑狼疮、特发性炎症性肌病和系统性硬化症患者中评估ALLO-329的疗效和安全性，预计在2025年年中展开。 ALLO-329是一款靶向CD19和CD70两个靶点的CAR-T细胞疗法，可靶向CD19阳性B细胞和CD70阳性激活T细胞。这一策略可能同时针对B细胞和T细胞功能失常，从而带来更好的治疗效果。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] SAB BIO Announces Positive Topline Phase 1 Clinical Results. Retrieved January 28, 2025, from https://www.globenewswire.com/news-release/2025/01/28/3016248/0/en/SAB-BIO-Announces-Positive-Topline-Phase-1-Clinical-Results-with-Potentially-Disease-Modifying-T1D-Therapy-SAB-142.html [2] Allogene Therapeutics Secures U.S. FDA IND Clearance for ALLO-329, Advancing its Next-Generation Allogeneic CAR T into Autoimmune Diseases. Retrieved January 28, 2025, from  https://www.globenewswire.com/news-release/2025/01/28/3016394/0/en/Allogene-Therapeutics-Secures-U-S-FDA-IND-Clearance-for-ALLO-329-Advancing-its-Next-Generation-Allogeneic-CAR-T-into-Autoimmune-Diseases.html [3] Vincerx Pharma, Inc. and Oqory, Inc. Highlight Promising Data for Oqory’s TROP2 Antibody Drug Conjugate, OQY-3258. Retrieved January 29, 2025, from https://investors.vincerapharma.com/news-releases/news-release-details/vincerx-pharma-inc-and-oqory-inc-highlight-promising-data-oqorys [4] Bicara Therapeutics Presents Phase 1/1b Dose Expansion Results with Ficerafusp Alfa in Advanced Squamous Cancer of the Anal Canal at the 2025 ASCO Gastrointestinal Cancers Symposium. Retrieved January 29, 2025, from https://ir.bicara.com/news-releases/news-release-details/bicara-therapeutics-presents-phase-11b-dose-expansion-results [5] GT Biopharma Announces First Patient Dosed in Phase 1 Trial of GTB-3650, Second-Generation TriKE for the Treatment of Hematologic Malignancies. Retrieved January 29, 2025, from https://www.gtbiopharma.com/news-media/press-releases/detail/288/gt-biopharma-announces-first-patient-dosed-in-phase-1-trial [6] Sapience Therapeutics Presents ST316 Phase 1 Dose Escalation Data at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium. Retrieved January 29, 2025, from https://sapiencetherapeutics.com/sapience-therapeutics-presents-st316-phase-1-dose-escalation-data-at-the-2025-american-society-of-clinical-oncology-asco-gastrointestinal-gi-cancers-symposium/ [7] Tectonic Therapeutic Announces Positive Interim Data from Phase 1b Trial for TX45 in Patients with Group 2 Pulmonary Hypertension in HFpEF. Retrieved January 30, 2025, from https://www.globenewswire.com/news-release/2025/01/30/3017839/0/en/Tectonic-Therapeutic-Announces-Positive-Interim-Data-from-Phase-1b-Trial-for-TX45-in-Patients-with-Group-2-Pulmonary-Hypertension-in-HFpEF.html [8] Tubulis Announces First Patient Dosed in Phase I/IIa Trial Evaluating ADC TUB-030 in Advanced Solid Tumors. Retrieved January 30, 2025, from https://www.businesswire.com/news/home/20250130888316/en [9] Creative Medical Technology Holdings Announces Positive Initial Safety, Tolerability, and Efficacy Data from First Cohort in Phase 1/2 Trial of CELZ-201-DDT for Chronic Back Pain. Retrieved January 30, 2025, from https://www.globenewswire.com/news-release/2025/01/30/3018142/0/en/Creative-Medical-Technology-Holdings-Announces-Positive-Initial-Safety-Tolerability-and-Efficacy-Data-from-First-Cohort-in-Phase-1-2-Trial-of-CELZ-201-DDT-for-Chronic-Back-Pain.html [10] Ethris Presents Positive Topline Phase 1 Data with mRNA Lead Candidate ETH47 for Uncontrolled Asthma. Retrieved January 30, 2025, from https://www.businesswire.com/news/home/20250130943965/en [11] Owkin Announces First Patient Dosed in Phase I AI-optimized Clinical Trial of OKN4395, a First-in-Class EP2/EP4/DP1 Triple Inhibitor for Patients with Solid Tumors. Retrieved January 30, 2025, from https://www.businesswire.com/news/home/20250130436779/en 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新