A Phase I Safety and Feasibility Study of Cellular Immunotherapy for Extensive Stage Small Cell Neuroendocrine Prostate Cancer Using Autologous T Cells Lentivirally Transduced to Express L1CAM-Specific Chimeric Antigen Receptor

This phase I trial studies the side effects and best dose of autologous CD8+ and CD4+ lentivirally transduced to express L1CAM-specific chimeric antigen receptor (CAR) and EGFRt mutation specific T cells and to see how well they work in treating patients with small cell neuroendocrine prostate cancer (SCNPC) that has spread to nearby tissue or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's tumor cells is added to the T cells in the laboratory. Some solid tumor cells have an L1CAM protein on their surface, and T cells can be modified with a receptor, called a chimeric antigen receptor (CAR), to help recognize this protein and kill these tumor cells. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. These L1CAM mutation specific T cells may help the body's immune system identify and kill L1CAM locally advanced and unresectable or metastatic small cell neuroendocrine prostate cancers' tumor cells.

开始日期2025-04-15

申办/合作机构

Fred Hutchinson Cancer Research Center

[+1]

NCT06561347

/ Not yet recruiting临床2期IIT

A Phase 2 Multicenter Study of the Combination Zanubrutinib, Bendamustine, and Rituximab in Previously Untreated Waldenström Macroglobulinemia (ZEBRA Trial)

The purpose of this study is to determine the very good partial response (VGPR) or better rate in participants with Waldenström macroglobulinemia (WM).
The names of the study drugs involved in this study are as follows: zanubrutinib, bendamustine, and rituximab.

开始日期2024-12-01

申办/合作机构

The General Hospital Corp.

[+1]

NCT06557330

/ Not yet recruiting临床2期IIT

HM-225: Measurable Residual Disease (MRD) Guided De-intensification of Bendamustine/Rituximab (BR) for Indolent Non-Hodgkin Lymphoma

This is a phase II pilot, single arm, open label study designed to assess the efficacy, safety, and feasibility of MRD adapted duration of BR for untreated or R/R iNHL.

开始日期2024-12-01

申办/合作机构

The Fox Chase Cancer Center

[+1]

100 项与盐酸苯达莫司汀相关的临床结果

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100 项与盐酸苯达莫司汀相关的转化医学

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100 项与盐酸苯达莫司汀相关的专利（医药）

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2,872

项与盐酸苯达莫司汀相关的文献（医药）

2025-01-01·EUROPEAN JOURNAL OF HAEMATOLOGY

Reduced Intensity Conditioning Prior Autologous Stem Cell Transplantation in Elderly DLBCL Patients

Article

作者: Engelhardt, Monika ; Finke, Jürgen ; Strüßmann, Tim ; Hermes, Philipp ; Duque‐Afonso, Jesús ; Marks, Reinhard ; Ihorst, Gabriele ; Duyster, Justus

ABSTRACT:

High‐dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is widely used in patients with diffuse large B‐cell lymphoma. HDCT/ASCT is associated with increased morbidity in elderly/unfit patients. We retrospectively evaluated the use of reduced intensity conditioning in DLBCL patients. Our study included 146 patients aged 60 years and older treated at our institution between 2005 and 2019; 86 patients received standard intensity conditioning (SI group) with BEAM or TEAM (BCNU or thiotepa, etoposide, cytarabine, melphalan). Sixty patients received reduced intensity high‐dose conditioning (RI group) with BM (BCNU, melphalan, 43.3%), TM (thiotepa, melphalan, 16.7%), BCNU or busulfan thiotepa (38.4%), or bendamustine melphalan (1.7%). Median follow‐up was 62.4 months. We observed comparable toxicities in the SI and RI groups. The cumulative incidence of relapse at 3 years was higher in the RI group (30.8% vs. 23.4%, p = 0.034). There was no difference in nonrelapse mortality (NRM). In univariate analyses, SI vs. RI conditioning resulted in superior progression‐free survival (PFS) (HR 1.80 CI 1.11–2.92, p = 0.017) but not in superior overall survival (OS) (HR 1.48 CI 0.86–2.56, p = 0.152). On multivariate analysis, we observed no difference in PFS (HR 0.74 CI 0.40–1.38, p = 0.345) and a trend toward better OS with RI conditioning (HR 0.45 CI 0.22–0.94, p = 0.032). Age 60–69 versus ≥ 70 years and remission prior to ASCT were the only factors predicting better PFS. Factors associated with better OS were RI conditioning, age 60–69 versus ≥ 70 years, ECOG 0 versus ≥ 1 performance status, bulky disease, and prior lines 1 versus ≥ 2. In conclusion, RI conditioning prior to ASCT may be feasible in elderly patients and led to a comparable outcome when corrected for several significant confounders.

2025-01-01·HEMATOLOGICAL ONCOLOGY

One‐Day Brentuximab–Bendamustine (120 mg/m2) Every 21 Days is a Feasible, Safe and Effective Treatment for Relapsed/Refractory Hodgkin Lymphoma

Article

作者: Madelaine‐Chambrin, I. ; Di Blasi, R. ; Brice, P. ; Schmidt‐Hieber, C. ; Wencel, J. ; Renaud, L. ; Delory, T. ; Laroque, M‐C. ; Thieblemont, C. ; Moatti, H. ; Ravdan, O.

ABSTRACT:

Brentuximab vedotin (BV)‐bendamustine (90 or 120 mg/m2 day 1 and 2) every 28 days is an effective treatment for relapsed/refractory Hodgkin lymphoma (R/R HL) but associated to high toxicity especially for elderly patients. We conducted in St Louis Hospital, Paris, between 2015 and 2021 a retrospective single‐center analysis of 44 patients with R/R HL treated with one‐day BV‐bendamustine (120 mg/m2) every 21 days. Sixteen percent of patients were ≥ 60 years old (yo). Seventy‐three percent of patients received total number of cycles without interruption nor adaptation. No patient ≥ 70 yo required treatment interruption. Dose adjustment was necessary for 18% of patients. Infusion‐related reaction (36%) occurred always at cycle 2 and was the only cause of treatment interruption. One febrile neutropenia, one non‐documented septic shock, one pyelonephritis on transplanted kidney and one COVID complicated by cytopenias were reported. Sixteen percent patients presented a peripheral sensory neuropathy, 7% and 4% respectively grade 3–4 neutropenia and thrombocytopenia. Overall response was 84%, with 73% of complete remission. Median progression‐free survival was of 19.8 months (95% CI 13.1‐NR) and median overall survival was not reached with a median follow‐up of 31 months. We suggest that one‐day BV‐bendamustine (120 mg/m2) ever 21 days is a safe and feasible treatment for R/R HL especially for elderly patients.

2024-12-31·JOURNAL OF MEDICAL ECONOMICS

Treatment patterns, healthcare resource utilization, and costs in Medicare patients with diffuse large B-cell lymphoma: a retrospective claims analysis (2015–2020)

Article

作者: Wang, Anthony ; Chhibber, Anindit ; Mutebi, Alex ; Kalsekar, Anupama ; Liang, Chenxue ; Keshishian, Allison ; He, Jing ; Jun, Monika P. ; Wang, Tongsheng ; Rivas Navarro, Fernando

AIMS:

To understand treatment patterns, healthcare resource utilization (HCRU), and the economic burden of diffuse large B-cell lymphoma (DLBCL) in elderly adults in the US.

MATERIALS AND METHODS:

This retrospective database analysis utilized US Centers for Medicare and Medicaid Services Medicare fee-for-service administrative claims data from 2015 to 2020 to describe DLBCL patient characteristics, treatment patterns, HCRU, and costs among patients aged ≥66 years. Patients were indexed at DLBCL diagnosis and required to have continuous enrollment from 12 months pre-index until 3 months post-index. HCRU and costs (USD 2022) are reported as per-patient per-month (PPPM) estimates.

RESULTS:

A total of 11,893 patients received ≥1-line (L) therapy; 1,633 and 391 received ≥2 L and ≥3 L therapies, respectively. Median (Q1, Q3) age at 1 L, 2 L, and 3 L initiation, respectively, was 76 (71, 81), 77 (72, 82), and 77 (72, 82) years. The most common therapy was R-CHOP (70.9%) for 1 L and bendamustine ± rituximab for 2 L (18.7%) and 3 L (17.4%). CAR T was used by 14.8% of patients in 3 L. Overall, 39.6% (1 L), 42.1% (2 L), and 47.8% (3 L) of patients had all-cause hospitalizations. All-cause mean (median [Q1-Q3]) costs PPPM during each line were $22,060 ($20,121 [$16,676-$24,597]) in 1 L, $30,027 ($20,868 [$13,416-$31,016]) in 2 L, and $47,064 ($25,689 [$15,555-$44,149]) in 3 L, with increasing costs driven primarily by inpatient expenses. Total all-cause 3 L mean (median [Q1-Q3]) costs PPPM for patients with and without CAR T were $153,847 ($100,768 [$26,534-$253,630]) and $28,466 ($23,696 [$15,466-$39,107]), respectively.

CONCLUSIONS:

No clear standard of care exists in 3 L therapy for older adults with relapsed/refractory DLBCL. The economic burden of DLBCL intensifies with each progressing line of therapy, thus underscoring the need for additional therapeutic options.

427

项与盐酸苯达莫司汀相关的新闻（医药）

2024-12-21

·生物制品圈

国内获批 ADC 药物

截至目前，全球获批ADC药物数量有16个，国内已获批上市十来款。根据智慧芽数据，有6个正处于上市申请阶段，进入临床试验阶段的偶联药物，处于Ⅰ期或Ⅰ/Ⅱ期的有两百多个，Ⅱ/Ⅲ期或Ⅲ期的三十多个。获批临床，及正在申请临床的均有十多个，近千个在临床前。对于ADC药物临床试验数据，国内现约一千五百条左右，其中肿瘤领域，约一千两百条，国内恒瑞医药、百利天恒、荣昌生物数据量名列前三，均近百条。国内已获批 ADC 药物恩美曲妥珠单抗（Kadcyla）恩美曲妥珠单抗是由抗 HER2 靶向药物曲妥珠单抗（人源化抗-HER2 IgG1 ），通过稳定的硫醚连接体 MCC（4-[N-马来酰亚胺甲基]环己烷-1-羧酸酯）与微管抑制药物 DM1（美坦辛衍生物）偶联而成，因此，也常被称为“T-DM1”。 MCC是一种稳定的硫醚连接体4-[N-马来酰亚胺甲基]环己烷-1-羧酸酯，为不可切割型连接子，无“旁观者效应”。曲妥珠单抗+强效化疗药DM1 图片来源：MDPI T-DM1药物结构，来源：Trastuzumab emtansine (T-DM1): a novel agent for targeting HER2+ breast cancer. 2013年2月22日在美国获批上市，用于早期和转移性HER2阳性乳腺癌的二线治疗。2020年1月21日，罗氏Kadcyla®（ado-trastuzumab emtansine，恩美曲妥珠单抗，赫赛莱®）获得国家药品监督管理局（NMPA）正式批准，是我国首个上市的抗体药物偶联物（ADC），也是全球首款被批准用于实体瘤的ADC。维布妥昔单抗（Adcetris®）注射用维布妥昔单抗（brentuximab vedotin，维布妥昔单抗，安适利®），靶向 CD30 的抗体偶联药物（ADC），由Seagen（原Seattle Genetics）原研，后来与Takeda联合开发。结构：针对CD30 靶点的本妥昔单抗Brentuximab+微管抑制剂 MMAE+二肽连接子（可被蛋白酶水解，具有一定的稳定性），随机偶联而成。作用机制：维布妥昔单抗靶向CD30阳性肿瘤细胞，并将微管破坏剂MMAE释放到肿瘤细胞内。维布妥昔单抗靶向CD30阳性肿瘤细胞，与肿瘤细胞表面CD30结合后，CD30复合物被细胞内吞，转运至溶酶体。连接桥被降解，微管破坏剂MMAE被释放到细胞内部，与细胞内的微管蛋白结合并破坏微管网络。这导致肿瘤细胞停滞在G2/M细胞周期并最终死亡。药物具有旁观者效应。 2011年8月,维布妥昔单抗(brentuximab vedotin,商品名Adcetris®)美国上市,适应症为：霍奇金淋巴瘤和系统性间变性大细胞淋巴瘤。 2020年5月,该药物以商品名安适利，获得NMPA批准国内上市（安适利® 维布妥昔单抗）。 2023年1月18日，注射用维布妥昔单抗被正式纳入国家医保，2023年3月1日开始实施，成为首个被纳入医保的CD30靶向ADC药物。纳入医保目录前，维布妥昔单抗（BV）价格为18680元/50mg/瓶，医保后价格降为7202元/50ml（降幅达54%）。奥加伊妥珠单抗/奥英妥珠单抗(Besponsa) 贝博萨(BESPONSA,通用名:奥加伊妥珠单抗,Inotuzumab Ozogamicin)，一款由美国辉瑞公司生产的靶向CD22的抗体-药物偶联物（ADC）。由靶向 CD22 的单克隆抗体（mAb）与细胞毒制剂卡奇霉素（calicheamicin）偶联。构成抗体：重组人源化免疫球蛋白G 亚型4（IgG4）kappa抗体伊珠单抗，可特异性识别人CD22； Linker：可酸解的连接子，由 4-(4'4-乙酰苯氧基)-丁酸 (AcBut) 和 3-甲基-3-巯基丁烷酰肼（被称为二甲酰肼，将 N-乙酰-γ-刺孢霉素与伊珠单抗共价结合）组成有效载荷：N-乙酰-γ-刺孢霉素，可导致双链DNA断裂小分子N-乙醯基γ-卡奇霉素是通过接头与抗体共价连接的细胞毒性剂。作用机制：ADC药物与CD22表达肿瘤细胞的结合，随后ADC-CD22复合物内化，N-乙醯基-γ-卡奇霉素二甲醯肼水解接头断裂。N-乙醯基-γ-卡奇霉素二甲基醯肼的活化诱导双链DNA断裂，随后诱导细胞周期停滞和凋亡细胞死亡。结构式： 2017年6月，奥加伊妥珠单抗首先在欧盟获批上市。 2017年08月17日，奥加伊妥珠单抗（商品名：Besponsa、Inotuzumab ozogamicin、奥加伊妥珠单抗）获美国FDA批准，适应症为：成人复发或难治性前B细胞急性淋巴细胞性白血病。 2020年12月，奥加伊妥珠单抗（曾用名：伊珠单抗奥唑米星）获NMPA批准上市，为国内首个获批上市的靶向CD22的抗体偶联药物（ADC），用于治疗复发性或难治性前体B细胞急性淋巴细胞白血病（ALL）的成年患者。 2024年，注射用奥加伊妥珠单抗参与了国谈，但未被纳入2024年医保目录。维迪西妥单抗维迪西妥单抗（RC48，爱地希）由靶向 HER2的人源化单抗、可裂解多肽 Mc-VC-PAB 连接子和细胞毒素 MMAE 通过半胱氨酸随机偶联而成的ADC药物，其 DAR值为 4。抗体：高 HER2亲和力新型人源化单抗Disitamab，EC50值为6.4pM，临床达标剂量更低。连接子：缬氨酸-瓜氨酸，具有胞内酶解特性，可实现在肿瘤细胞内精准释放高毒性的细胞毒素，降低对脱靶毒性，有望克服耐药。细胞毒素：MMAE，具有高膜穿透效应，具有较强的“旁杀效应”。作用机制：维迪西妥单抗的通过抗体部分结合至肿瘤表面的HER2 胞外结构域，在受体介导的内吞作用下，维迪西妥单抗被转运到溶酶体，连接子被酶剪切后，MMAE 细胞毒被释放到细胞内，从而破坏细胞内微管网络，致使细胞凋亡。 2021年6月9日，维迪西妥单抗获NMPA批准上市，适应症为至少接受过2种系统化疗的HER2过表达局部晚期或转移性胃癌患者。戈沙妥珠单抗戈沙妥珠单抗（Trodelvy®、Sacituzumab govitecan、IMMU-132）是全球首款获批上市的靶向 TROP-2 的抗体偶联药物（ADC），通用名为注射用戈沙妥珠单抗。结构：靶向 TROP-2 抗原的人源化 IgG1 抗体-hRS7(IgGk)，可水解的 Linker与化疗药物伊立替康（拓扑异构酶 I 抑制剂）的代谢活性产物 SN-38 偶联而成。具备旁观者杀伤效应。抗体部分：靶向 Trop 2 的人源化 hRS7 抗体； Linker：CL2A 可裂解连接子; Payload：DNA 拓扑异构酶Ⅰ抑制剂 SN-38；DAR为 7.6 图：Trodelvy 分子结构 2020年4月在美国以加速批准的方式暂时上市，用于先前已接受过至少两种疗法治疗的转移性三阴性乳腺癌（Metastatic triple-negative breast cancer，mTNBC）成人患者。 2022年，Trodelvy在新加坡获批用于治疗三阴性乳腺癌。 2022年6月7日，中国获批。泊洛妥珠单抗 Polivy 泊洛妥珠单抗（Polivy）是靶向CD79b的抗体-药物偶联物。特定蛋白质(CD79b)抗体与抗有丝分裂剂MMAE（单甲基阿司他丁E）偶联而成。作用机制：单抗与B细胞特异性表面蛋白CD79b结合后，将POLIVY泊洛妥珠单抗内化，并通过溶酶体蛋白酶切割linker，以实现MMAE的细胞内递送。MMAE结合微管，并通过抑制细胞分裂并诱导凋亡来杀死分裂中的细胞。 2019年6月，泊洛妥珠单抗（Polivy）获得FDA加速批准上市，主要与化疗药物苯达莫司汀和利妥昔单抗产品（称为“BR”组合）联合治疗成人弥漫性大B细胞淋巴瘤患者（DLBCL）； 2020年1月，Polivy在欧盟有条件的批准上市，适应症同样为成人弥漫性大B细胞淋巴瘤患者（DLBCL）的治疗。 2023年1月，Polivy®获得国家药品监督管理局（NMPA）正式批准。 Enhertu DS-8201商品名为Enhertu，靶点为HER2，由曲妥珠单抗、4肽可裂解连接子，和细胞毒药物依喜替康衍生物（拓扑异构酶1抑制剂）组成。抗体：Enhertu的抗体是人源化IgG1单克隆抗体，参照了曲妥珠单抗 (Trastuzumab, Herceptin, 赫赛汀) 相同的氨基酸序列，即赫赛汀的生物类似物连接子：DXd通过肽基间隔区 (甘氨酸-甘氨酸-苯丙氨酸-甘氨酸, Gly-Gly-Phe-Gly)与单抗共价连接 payload：采用了DNA拓扑异构酶抑制剂DXd，DXd活性是伊立替康的10倍，其毒性较小，半衰期较短，不易在体内发生蓄积。DAR高达8，高DAR搭配中等毒性Payload的组合。 DS-8201于2019年12月获美国FDA加快批准，适应症为乳腺癌，用于治疗三线治疗经治HER2阳性无法切除或转移性HER2阳性乳腺癌患者。随后欧盟和日本批准上市。 2023年2月，优赫得®（“德曲妥珠单抗”，代号DS-8201，商品名优赫得）首次获得NMPA批准国内上市，用于治疗既往接受过一种或一种以上抗HER2药物的不可切除或转移性HER2阳性成人乳腺癌患者。维恩妥尤单抗（恩诺单抗，EV，Padcev） Padcev是一款创新ADC药物，靶向连接蛋白-4（Nectin-4），由的人IgG1单克隆抗体enfortumab与细胞毒制剂MMAE(monomethyl auristatin E，单甲基奥瑞他汀E，一种微管破坏剂)偶联而成。作用机制：维恩妥尤单抗通过与表达Nectin-4蛋白的细胞结合，然后将抗肿瘤成分单甲基澳瑞他汀 E（MMAE）内化并释放到细胞中，导致细胞停止增殖（细胞周期阻滞）和程序性细胞死亡（凋亡）来发挥其抗癌活性。 2019年12月，美国FDA已批准Padcev用于治疗局部晚期或转移性尿路上皮癌患者。 2024年8月19日，注射用维恩妥尤单抗（Enfortumab Vedotin）获得中国国家药品监督管理局批准上市，是国内首款获批上市的靶向Nectin-4的ADC药物。获批适应症为治疗既往接受过PD-1/PD-L1抑制剂和含铂化疗治疗的局部晚期或转移性尿路上皮癌（mUC）患者。芦康沙妥珠单抗（sac-TMT,佳泰莱）芦康沙妥珠单抗为一款TROP2 抗体偶联药物（ADC），由具有高亲和力和靶向性的人源化抗TROP2单抗，通过稳定性经过优化的CL2A连接子与毒素小分子T030（拓扑异构酶Ⅰ抑制剂）偶联而成，药物抗体比（DAR）平均高达7.49-11 2024年11月27日，TROP2 抗体偶联药物（ADC）——芦康沙妥珠单抗，获中国药品监督管理局（NMPA）批准上市，用于治疗既往至少接受过2种系统治疗（其中至少1种治疗针对晚期或转移性阶段）的不可切除的局部晚期或转移性三阴性乳腺癌成人患者。注射用替朗妥昔单抗替朗妥昔单抗是一款CD19靶向ADC药物，由CD19单克隆抗体通过连接子与PBD（吡咯并苯并二氮杂卓）二聚体细胞毒素偶联而成。作用机制：替朗妥昔单抗与表达CD19的肿瘤细胞结合时会被细胞内化，随后释放吡咯并苯二氮杂䓬二聚体（PBD）细胞毒素。PBD与DNA小沟结合，形成强效的细胞毒性DNA链间交联，导致DNA复制停滞，阻断细胞周期从而导致肿瘤细胞死亡。 2021年4月，替朗妥昔单抗获美国FDA加速批准，用于治疗至少接受过2线及以上系统治疗的复发或难治性弥漫大B细胞淋巴瘤（r/r DLBCL）成年患者。 2022年12月，替朗妥昔单抗获得欧洲药品管理局（EMA）的附条件批准。 2024年12月10日，注射用替朗妥昔单抗（Loncastuximab tesirine）上市申请获得国家药品监督管理局批准，是国内首个获批上市的CD19 ADC药物，其适应症为单药治疗复发/难治性弥漫性大B细胞淋巴瘤(R/R DLBCL)。趋势 2025年预计将有多款ADC药物在国内获批，中国 ADC 市场有望迅速增长。 ADC交易热度维持高位,出海模式逐年丰富升级。 ADC 技术升级改造，ADC 药物和 IO 药物联用、双抗 ADC 等。识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

抗体药物偶联物上市批准临床2期临床结果

2024-12-19

·ioncology

Best of ASH丨年度盘点：恶性血液病领域重磅研究进展一文全览

编者按 2024年12月7日至10日，第66届美国血液学会（ASH）年会在美国圣迭戈隆重召开，全球血液学专家学者齐聚一堂，共同对血液领域最新研究进展进行深入探讨与交流。在本届大会上，杰克逊实验室Jennifer Trowbridge博士作为科学项目联合主席，在备受期待的“Best of ASH”环节中回顾并总结了本次大会在恶性血液病研究领域所呈现的亮点内容，不仅代表了当前血液学研究的最前沿动态，也预示着未来该领域的发展方向与潜在突破。《血液时讯》特整理成文，以期与广大读者共享这场学术盛宴的丰硕成果。克隆性造血中的克隆选择与新机制 01 体内条形码CRISPR-Cas9筛选技术鉴定出Ncoa4介导的铁蛋白自噬是TET2缺陷型造血过程中的一种依赖性机制（摘要号：188） TET2基因突变在血液系统恶性肿瘤中颇为常见，然而，关于这些突变细胞如何存活并增殖的具体机制，目前医学界尚未完全明晰。Justin C.T. Loke团队成功运用条形码CRISPR-Cas9筛选技术，深入揭示了TET2缺陷造血干/祖细胞（HSPCs）的遗传依赖性。该项研究巧妙地突破了传统体内CRISPR筛选技术的局限性，创新性地采用带有条形码的单向导RNA（sgRNA），来追踪TET2缺失模型下特定克隆的适应性和扩展情况，从而提供了前所未有的深刻洞察。铁蛋白自噬是指通过溶酶体降解铁蛋白以释放铁的过程，它在维持线粒体功能方面发挥着举足轻重的作用。研究发现，NCOA4作为铁蛋白自噬过程的关键调控因子，在TET2缺陷HSPCs的遗传依赖性中扮演着至关重要的角色。在TET2缺陷的细胞中，NCOA4介导的铁蛋白自噬显著促进了线粒体ATP的生成，这一过程对于维持克隆的适应性和扩展至关重要。当NCOA4缺失时，这些克隆的增殖能力受到明显抑制，存活率也大幅下降，进一步强调了NCOA4作为潜在“合成致死”靶点的重要性。具体而言，研究中设计了一套条形码CRISPR-Cas9筛选方案，该方案涵盖了一个包含超过2000个基因的条形码CRISPR-Cas9库，并结合了尖端的sgRNA跟踪技术，从而能够以前所未有的高分辨率监测TET2野生型及缺失模型中的克隆行为。通过对克隆数量和规模进行详尽的比较分析，发现TET2缺失的细胞展现出了独特的克隆动态变化。特别是当NCOA4被删除时，TET2缺陷克隆的扩展受到了显著抑制，而野生型克隆则未受影响。这一发现提示我们NCOA4在TET2缺陷细胞中的重要性。为了进一步验证，研究者进行了单细胞RNA测序分析，结果显示，TET2缺陷的造血干/祖细胞对铁蛋白自噬途径的依赖性显著增加。当NCOA4缺失时，这些途径受到破坏，导致线粒体功能障碍及竞争适应性的丧失。功能验证实验则进一步强调了NCOA4在维持能量代谢中的关键作用：靶向NCOA4可显著减少TET2缺陷细胞中的线粒体ATP生成。除了NCOA4之外，还识别了其他可能影响TET2缺陷环境中克隆规模和数量的候选基因。这些基因在未来有可能成为辅助治疗的新靶点。值得注意的是，传统CRISPR筛选方法主要关注克隆数量的变化，可能会忽视与克隆适应性相关的重要依赖性，而通过引入条形码sgRNA，成功检测到克隆行为的细微变化，如规模和竞争优势的转变，从而提供了更全面的TET2突变造血遗传景观的见解。因此，NCOA4作为关键依赖性的识别为TET2突变驱动的克隆性造血和血液系统恶性肿瘤的治疗提供了新的治疗机会。通过抑制NCOA4介导的铁蛋白自噬，有望选择性地靶向TET2缺陷细胞，而对正常HSPCs的影响较小。这一策略有望被整合到相关疾病的治疗体系中，以减轻疾病负担，同时最大限度地降低毒性。 02 DNMT3A通过非DNA甲基化途径的端粒调控来控制造血干细胞（摘要号：25） Infencia Xavier Raj团队主导的最新研究深入探讨了DNA甲基转移酶3A（DNMT3A）在造血干细胞调控中非DNA甲基化机制的关键作用。该研究表明，即便在不涉及DNMT3A的传统DNA甲基化功能的情况下，DNMT3A缺失的HSC仍表现出显著的扩增现象，体现了存在其他调控途径在调控干细胞动态和适应性方面发挥着重要作用。研究结果揭示了几个重要发现：首先，DNMT3A缺失的HSC拥有更长的端粒，这一特征与其增强的自我更新能力和功能直接相关。这表明端粒长度是决定HSC竞争优势的关键因素之一，对其再生能力具有显著影响。其次，在端粒酶依赖的背景下，缺失DNMT3A的HSC获得了明显的竞争优势，这进一步证实了端粒生物学与干细胞调控之间存在密切的相互作用。此外，研究还强调，DNMT3A的功能不仅局限于其甲基转移酶活性，而是能够通过新的途径来调节干细胞的分化和增殖。竞争性移植实验显示，即使在甲基转移酶活性部分或完全丧失的情况下，DNMT3A缺失的HSC仍保持了卓越的功能适应性，凸显了DNMT3A改变所带来的端粒相关优势的强大作用。因此，该项研究为探索以端粒为中心的治疗干预措施在血液恶性肿瘤或干细胞功能障碍等病症中的应用提供了重要启示。同时，它也提出了关于DNMT3A所调控的替代分子途径的关键问题，这些途径可能揭示新的治疗靶点，从而进一步推动干细胞治疗方法的发展，为生物学及转化应用的深入理解开辟了新的道路。 03 工程化端粒酶RNA组分（eTERC）：一种潜在的长非编码RNA（lncRNA）药物，用于延长先天性角化不良患者干细胞的复制寿命和端粒长度（摘要号：443） Neha Nagpal与Suneet Agarwal的研究深入探索了eTERC在治疗端粒生物学相关疾病，尤其是先天性角化不良（DKC）方面的潜力。研究指出，通过有效增强端粒长度，eTERC可为缓解由端粒功能缺失引发的疾病提供一种创新的治疗策略。 TERC的缺失与多种疾病密切相关，包括但不限于骨髓衰竭、骨髓增生异常综合征/白血病、肺纤维化以及肝病等。因此，恢复TERC的功能对于治疗这些疾病至关重要。然而，传统的体外转录（IVT）TERC方法存在局限性，如RNA易降解、折叠不正确以及亚细胞定位错误等，这些问题限制了其有效延长端粒长度的能力，凸显了改进RNA设计的迫切需求。这项研究中，通过将eTERC瞬时引入DKC患者来源的诱导多能干细胞（iPSC）中，成功恢复了端粒酶活性，并显著增加了端粒长度。这一结果表明，eTERC可以功能性地整合到端粒酶复合物中，实现了在端粒延长方面的突破。此外，eTERC在增强干细胞端粒长度和复制能力方面展现出了体外（ex vivo）细胞治疗的巨大潜力，不仅为DKC治疗提供了新的思路，还可能拓展至其他与端粒功能相关的疾病领域，具有广泛的应用前景。综上，eTERC可作为治疗端粒相关疾病的变革性工具，为恢复端粒功能、改善DKC等遗传疾病开辟了一条创新的RNA基因治疗路径。急性髓系白血病的新兴治疗策略 01 靶向蛋白质降解揭示MECOM在高危急性髓系白血病中通过CEBPA位点抑制分化的作用（摘要号：953） Zeng团队的研究深入剖析了MDS1和EVI1复杂基因（MECOM）在急性髓系白血病（AML）中发挥的关键作用，揭示了其推动侵袭性、干细胞样分子程序的重要机制。该团队利用CRISPR-Cas9技术全面展示了干扰MECOM调控通路以改善AML临床结局的治疗潜力。 AML细胞具有异质性特征，其中原始的干细胞样表达程序与较差生存率密切相关。MECOM、GATA2等特定的基因改变定义为AML的高危亚组，这些患者表现出尤为侵袭性的疾病特征。通过CRISPR-Cas9筛选，研究团队鉴定了MECOM在AML细胞中直接调控的顺式调控元件（CREs），并发现其中一个特定的CEBPA顺式调控元件受到MECOM的抑制，从而维持了AML细胞的高危、干细胞样状态。进一步研究表明，靶向MECOM抑制的CEBPA顺式调控元件可以重新激活CEBPA的表达，进而促进AML细胞的分化。体内模型显示，这一干预措施显著降低了白血病细胞负荷，并伴随着分化标志物的改善。此外，来自原发AML患者样本的数据也证实了MECOM对CEBPA的抑制作用在不同AML亚型中具有一致性。通过重激活CEBPA顺式调控元件，观察到CD34表达的提高，进一步支持了其在靶向AML干细胞样状态中的治疗相关性。综上所述，该研究成果为探索MECOM靶向疗法在AML中的应用提供了坚实的理论基础和实践框架，为攻克高危AML开辟了创新性的治疗路径，有望为改善患者预后提供新的策略和方法。 02 针对突变型钙网蛋白肿瘤的首创CAR-T疗法的开发及其在相关人体组织环境中的评估（摘要号：871）在针对由钙网蛋白突变（mutCALR）驱动的骨髓性肿瘤的研究中，CAR-T细胞疗法展现了令人瞩目的成果，标志着精准免疫治疗领域的重要进步。该研究表明，CAR-T细胞疗法不仅具有高度特异性和高效性，而且能够与现有的治疗方法协同作用，为耐药病例提供了新的治疗选择。首先，CAR-T细胞疗法展示了其选择性清除携带mutCALR的造血干细胞的能力，在不同等位基因频率背景下，实现了60%～70%的杀伤效率。这一高特异性与高效性意味着该疗法能够在不损害正常组织的情况下，有效地靶向并消除肿瘤细胞，从而提高治疗的安全性和有效性。其次，研究发现艾曲波帕在增强mutCALR/TPO-R表达方面表现出显著优势，这与罗普司亭的作用形成对比。艾曲波帕的应用不仅提升了CAR-T细胞对mutCALR阳性细胞的识别和攻击能力，还在治疗晚期骨髓纤维化（加速期和急变期；AP/BP MF）中提高了整体疗效。此外，正在接受JAK抑制剂治疗患者的CAR-T细胞仍保留其功能性，这提示了CAR-T疗法在耐药病例中的潜在应用价值。对于那些对传统治疗反应不佳或产生耐药性的患者，CAR-T细胞疗法可成为一种有效的补充手段，整合到现有的治疗方案中，提供更多的治疗选项。最后，mutCALR被鉴定为一种肿瘤特异性新抗原，是目前处于I期临床试验中的单克隆抗体和双特异性T细胞疗法的有价值靶点。这一发现强调了mutCALR在精准医学中的重要性，并为开发更高效的个性化治疗策略奠定了基础。综上所述，这项研究不仅证明了CAR-T细胞疗法在mutCALR驱动型肿瘤治疗方面的潜力，还为未来探索更多基于免疫治疗的创新疗法提供了重要的参考依据。随着研究的深入和技术的进步，相信针对mutCALR的CAR-T细胞疗法将为这类疾病患者带来更为光明的治疗前景。多发性骨髓瘤和骨髓增殖性肿瘤的预防和干预治疗 01 达雷妥尤单抗单药治疗与积极监测在高危冒烟型多发性骨髓瘤患者中的比较：AQUILA研究的主要结果（摘要号：773） Meletios-Athanassios Dimopoulos团队开展的AQUILA研究，为我们提供了关于高危冒烟型多发性骨髓瘤（SMM）管理的重要见解。AQUILA研究是一项大型的随机III期临床试验，其核心目的在于对比达雷妥尤单抗（DARA）单药治疗与积极监测两种策略在高危SMM患者中的应用效果，并着重评估二者对疾病进展状况以及安全性方面的影响。研究于23个国家的124个医疗中心招募了390例患者，随机分配接受DARA单药治疗或积极监测。主要终点是无进展生存期（PFS），次要终点包括总体缓解率（ORR）、转为多发性骨髓瘤的一线治疗时间以及安全性。研究显示，与积极监测组相比，接受DARA治疗的患者其疾病进展风险降低约50%（HR：0.49；95%CI：0.36–0.67），中位PFS尚未达到，而积极监测组中位PFS为41.5个月。此外，DARA组显著减少了根据SLiM-CRAB标准所定义的骨病以及其他疾病相关事件的发生。安全性方面，DARA组仅有5.7%的患者因不良事件停止治疗。其中，较为常见的不良事件主要包括高血压（5.7%）和肺炎（3.6%），未发现新的安全性问题。综上所述，AQUILA强调了DARA在延缓高危惰性多发性骨髓瘤进展过程中的潜力，为该疾病领域提供了一种极为重要的治疗选择。同时，该研究也进一步支持了早期干预SMM的益处，并确保了治疗的安全性和耐受性。这些发现为优化患者管理方案提供了强有力的证据，有望推动高危SMM治疗策略的进一步发展。淋巴细胞白血病和淋巴瘤的标准治疗考虑因素 01 固定疗程的阿可替尼+维奈克拉±奥妥珠单抗，与化疗免疫疗法在慢性淋巴细胞白血病一线治疗中的比较：多中心、开放标签、随机、III期AMPLIFY试验的中期分析（摘要号：1009）在慢性淋巴细胞白血病（CLL）的治疗进程中，Jennifer R. Brown团队开展的AMPLIFY试验具有里程碑式的重要意义，其为CLL治疗领域带来了关键的进展。AMPLIFY试验作为一项III期研究，致力于全面对比不同治疗方案在CLL治疗中的疗效与安全性。具体而言，该研究将两种固定疗程治疗方案，即阿可替尼（acalabrutinib）、维奈克拉（venetoclax）和奥妥珠单抗（obinutuzumab）联合治疗方案（AVO）以及阿可替尼和维奈克拉联合治疗方案（AV），与传统的化学免疫疗法（氟达拉滨+环磷酰胺+利妥昔单抗[FCR]/苯达莫司汀+利妥昔单抗[BR]）进行了深入比较。研究显示，AV和AVO方案在PFS和OS方面均展现出相较于传统疗法的显著优势。在PFS方面，AV组的HR达到0.65（95%CI：0.30-0.87，P=0.0038），AVO组的HR更是低至0.42（95%CI：0.30-0.59，P<0.0001）。在OS方面，即便在排除与COVID-19相关的死亡数据后，AV和AVO方案依然表现卓越。其中，AVO方案在36个月时的OS率高达97.5%，AV方案也达到了96.2%，相比之下，传统的FCR/BR方案的OS率仅为93.7%。安全性方面，AV和AVO方案展现出了良好的耐受性。尤为重要的是，其心脏不良事件的发生率较低，这一特性成功地解决了以往BTK抑制剂的相关缺点，使得AV和AVO方案能够适用于更为广泛的患者群体，为不同病情和身体状况的患者提供了可行的治疗选择。综上所述，AMPLIFY试验的研究意义深远而重大，强调了以固定疗程为目标的靶向治疗策略在实现CLL患者持续缓解病情的同时，能够显著降低长期毒性风险。这一有力的证据进一步巩固了靶向疗法在重塑初治CLL标准治疗模式中的核心地位，为未来CLL治疗策略的优化和发展提供了坚实的依据，有望推动临床实践朝着更精准、更有效的方向迈进。 02 伊布替尼联合利妥昔单抗方案在既往未经治疗的老年套细胞淋巴瘤患者中优于利妥昔单抗联合化疗方案：ENRICH研究结果（摘要号：235） David John Lewis团队主导的ENRICH研究是一项重要的III期随机研究，深入探讨了伊布替尼联合利妥昔单抗（IR）与免疫化疗（R-化疗）在未经治疗的老年套细胞淋巴瘤（MCL）患者中的疗效和安全性，旨在针对这一侵袭性淋巴瘤，特别是老年患者的治疗策略提供详尽且优化的数据支持。研究显示，IR方案在延长PFS方面展现出了显著优势：与R－化疗相比，IR组中位PFS达65.3个月，而R-化疗组为42.4个月，彰显了IR方案在控制疾病进展方面的潜力。在安全性方面，IR方案的不良事件特征与伊布替尼的已知副作用一致，但相较于R－化疗，其血液毒性更低，显著减少了贫血、白细胞减少等副作用的发生。这对于体质较弱、更易受化疗毒性影响的老年患者而言尤为重要。同时，在生活质量（QOL）方面，IR组患者在治疗初期即表现出明显改善，并持续至整个治疗过程中。与R-化疗相比，IR组在减轻治疗相关疲劳、疼痛及生活干扰方面展现出显著优势，有望优化老年患者的治疗体验。此外，IR方案在多种患者群体中均表现出一致的疗效，尤其在非母细胞样和Ki67指数较低的患者中显得尤为突出，通常这些患者预后较差，但在IR方案治疗下仍能获得显著的生存获益和生活质量改善。在R-CHOP方案亚组中，IR的疗效尤为显著，与苯达莫司汀-R亚组相比，其PFS显著延长，提示不同的初始治疗方案可能会影响后续治疗的疗效。因此，ENRICH试验的结果不仅肯定了IR方案在未经治老年MCL患者中的潜在标准治疗地位，更在延长PFS、降低毒性及改善生活质量方面提供了全新的治疗选择，不仅为未来IR方案的广泛推广奠定了坚实基础，同时也推动了对MCL高危患者更安全、更有效治疗方法的深入探索。 03 成人复发/难治性转化性惰性淋巴瘤患者接受CD19 CAR-T细胞疗法的真实世界结果（摘要号：524） Swetha Kambhampati Thiruvengadam团队开展的这项研究，为我们揭示了CD19 CAR-T细胞疗法在治疗转化型惰性非霍奇金淋巴瘤（tiNHL）患者中的变革性潜力。tiNHL作为高风险亚组，源于惰性非霍奇金淋巴瘤向侵袭性大B细胞淋巴瘤的恶性进展，患者常常面临疾病控制效果差、化疗耐药以及OS较低的挑战。研究结果表明，在CD19 CAR-T治疗后，tiNHL患者实现了比原发性aLBCL更高的CR率，且PFS和OS与原发性病例相当，表明CD19 CAR-T疗法在该类患者中具有显著的疗效。在安全性方面，细胞因子释放综合征（CRS）和免疫效应细胞相关神经毒性综合征（ICANS）的出现时间更晚，严重程度更低，且ICANS相关的糖皮质激素需求较低，进一步证实了CD19 CAR-T疗法的良好安全性。此外，该研究还确定了影响CD19 CAR-T治疗PFS的关键风险因素，包括乳酸脱氢酶（LDH）水平升高、晚期疾病状态、≥3线的既往治疗方案、近期苯达莫司汀治疗史、中枢神经系统（CNS）受累以及桥接治疗。这些风险因素的识别为临床医生提供了优化患者管理的重要指导。总体而言，这项研究进一步巩固了CD19 CAR-T疗法在满足tiNHL患者未被满足治疗需求中的关键作用，尤其是对于那些不具备上述不良风险因素的患者，CD19 CAR-T疗法展现出显著的治疗优势。总结在本次“Best of ASH”环节中，对一系列推动血液系统恶性肿瘤管理进程的重要研究进行了全面且深入的回顾。这些研究着重凸显了靶向疗法以及创新药物组合所蕴含的变革性潜力，它们在改善疗效方面取得了令人瞩目的显著成果，为血液系统恶性肿瘤患者的治疗带来了新的希望与可能。与此同时，众多研究团队高度关注并突出了降低治疗相关毒性的重要意义，且预防性策略与早期干预理念正逐步融入临床实践的主流，这些趋势深刻体现了血液学领域向精准医学方向转变的决心。未来治疗决策有望更加优先考量疗效与患者生活质量之间的平衡，力求在确保疾病有效控制的同时，最大程度减轻患者因治疗而承受的负担，提升其生活品质。这些研究成果不仅为将前沿研究成果整合至日常临床实践提供了清晰明确的路径，更为构建以患者结局和福祉为首要考量、高度个性化的治疗模式奠定了坚实的基础，对未来领域治疗和管理具有深远的指导意义。（来源：《肿瘤瞭望–血液时讯》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

基因疗法核酸药物

2024-12-18

·PRNewswire

Cancer Care Disruptions Highlight Growing Demand for Innovative Oncology Treatments

USA News Group Commentary Issued on behalf of Oncolytics Biotech Inc. VANCOUVER, BC, Dec. 18, 2024 /PRNewswire/ -- USA News Group News Commentary – The American Cancer Society recently released its Advances in Oncology – 2024 Research Highlights report that highlighted how their scientists continued to set the standard for research and innovation over the course of the year. However, along with the report's optimism, the American Cancer Society also recently released a study finding that early-onset colorectal cancer cases are surging globally, signaling an alarming trend. A new article published in Nature showed that the COVID-19 pandemic severely disrupted cancer care, causing delays in diagnosis, treatment, and screening services, which likely led to more advanced disease stages, poorer survival outcomes, and significant challenges in accurately interpreting long-term cancer survival data. In the world of oncology, there are still several challenges that need to be addressed and new treatments to be rolled out, but thankfully, there have been several recent developments coming out from innovators, including O ncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), Cardiff Oncology, Inc. (NASDAQ: CRDF), OS Therapies, Inc. (NYSE-American: OSTX), Checkpoint Therapeutics, Inc. (NASDAQ: CKPT), and Eli Lilly and Company (Lilly) (NYSE: LLY). The article continued: Not long ago, the American Cancer Society sounded the alarm on a surging rise in cancer diagnoses and fatalities among younger. For the industry targeting the alarming issue, analysts at Exactitude Consultancy project the Cancer Immunotherapy Market to expand at a 12.84% CAGR, reaching $258.22 billion by the end of 2031, further solidifying oncology as a dynamic and evolving sector. Oncolytics Biotech® to Present Promising Pelareorep Data in Pancreatic and Anal Cancers at ASCO GI Symposium Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, today announced the presentation of two data sets through two abstracts showcasing pelareorep's potential in difficult-to-treat gastrointestinal cancers, which were accepted and will be presented at the 2025 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco January 23-25, 2025. "We are enthusiastic about pelareorep's applicability across multiple gastrointestinal cancer indications, including pancreatic and anal cancer," said Tom Heineman, M.D., Ph.D., Chief Medical Officer of Oncolytics. "Pelareorep engages patients' immune systems to help make commonly used chemotherapies and checkpoint inhibitors, such as atezolizumab, more effective in fighting cancer. This offers the promise of delaying disease progression and improving survival in patients with these devasting diseases. Given the versatility of pelareorep, we see multiple clinical and regulatory options for bringing this promising medicine to patients." Oncolytics will present two key data sets from the GOBLET study, with preliminary safety and tumor response results for the relapsed anal carcinoma cohort treated with pelareorep and atezolizumab presented in Poster Session C on January 25, 2025, from 7:00 to 7:55 a.m. PT. Additionally, results from the safety run-in phase for first-line metastatic pancreatic ductal adenocarcinoma patients treated with pelareorep, modified FOLFIRINOX, with and without atezolizumab will be presented in Poster Session B on January 24, 2025, from 11:30 a.m. to 1:00 p.m. PT. Both abstracts will be available on the ASCO Gastrointestinal Cancers Symposium website at 5:00 p.m. ET on January 21, 2025. CONTINUED… Read this and more news for Oncolytics Biotech at: In other recent industry developments and happenings in the market include: Cardiff Oncology, Inc. (NASDAQ: CRDF), a clinical-stage biotechnology company leveraging PLK1 inhibition to develop novel therapies across a range of cancers, recently announced positive initial data from CRDF-004, a randomized, Phase 2 clinical trial evaluating onvansertib in combination with standard-of-care (SoC) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC). Efficacy and safety data are for all evaluable patients as of a November 26, 2024, data cut-off date, and all efficacy data are determined by a blinded, independent central review (BICR) of each patient's tumor scan. "We are highly encouraged by the robust efficacy signal and favorable safety profile observed with onvansertib plus standard-of-care from the first 30 evaluable patients in our randomized first-line RAS-mutated mCRC CRDF-004 trial," said Fairooz Kabbinavar, MD, FACP, Chief Medical Officer of Cardiff Oncology. "Our data shows an objective response rate of 64% in patients receiving the 30 mg dose of onvansertib in combination with standard of care, significantly higher than the 33% objective response rate observed in the control arms of standard of care alone. In addition, as can be seen in the spider plots, we are observing deeper tumor response in patients receiving the 30mg dose of onvansertib compared to those receiving the 20mg dose with similar safety profiles for both doses." OS Therapies, Inc. (NYSE-American: OSTX), a clinical-stage cancer immunotherapy and antibody-drug conjugate biotechnology company, recently reported its Q3 2024 financial results for the quarter and provided a business update. Within the quarter, OS Therapies completed dosing all patients in its potentially pivotal Phase 2b clinical trial of OST-HER2 for resected, recurrent osteosarcoma and is preparing to release topline data in December. The company also joined Johnson & Johnson's JLABS program, completed its IPO on the NYSE American, and is in active discussions with the FDA regarding Breakthrough Therapy Designation for OST-HER2. "The third quarter was pivotal for OS Therapies as we completed our initial public offering and finished dosing the final patient enrolled in our Phase 2b clinical trial of OST-HER2 in resected, recurrent osteosarcoma," said Paul Romness, MHP, Chairman and CEO of OS Therapies. "We are now looking forward to releasing topline data in December and then engaging with the FDA regarding getting this potentially life-saving cancer immunotherapy to patients that have no other potential treatment options as quickly as possible." Checkpoint Therapeutics, Inc. (NASDAQ: CKPT), a commercial-stage immunotherapy and targeted oncology company focused on novel treatments for patients with solid tumor cancers, recently announced that the FDA approved its UNLOXCYT™ (cosibelimab-ipdl) for the treatment of adults with metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC who are not candidates for curative surgery or curative radiation. UNLOXCYT is the first and only programmed death ligand-1 (PD-L1) blocking antibody to receive FDA marketing approval for this indication. "[This] FDA approval of UNLOXCYT – the first marketing approval for our company – is a significant milestone both for Checkpoint and for patients with advanced cSCC," said James Oliviero, President and CEO of Checkpoint. "This approval marks Checkpoint's transformation to a commercial-stage company, with the opportunity to compete in a U.S. market estimated to exceed $1 billion annually, where we believe UNLOXCYT offers a differentiated treatment option versus available therapies by binding to PD-L1, rather than programmed death receptor-1 (PD-1), to release the inhibitory effects of PD-L1 on the anti-tumor immune response. Additionally, UNLOXCYT has demonstrated the ability to induce antibody-dependent cell-mediated cytotoxicity (ADCC), another potential differentiating feature of the drug compared to existing marketed therapies for patients with cSCC." Eli Lilly and Company (Lilly) (NYSE: LLY), a medicine company turning science into healing to make life better for people around the world, recently announced results from its Phase 3 BRUIN CLL-321 trial, which tested pirtobrutinib, a next-generation treatment for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously been treated with a similar type of drug. The study showed that pirtobrutinib significantly reduced the risk of disease progression or death by 46% compared to standard treatments (idelalisib plus rituximab or bendamustine plus rituximab). These promising results were presented at the 66th American Society of Hematology (ASH) Annual Meeting. "BRUIN CLL-321 is the only randomized CLL or SLL study ever conducted exclusively in the BTK-inhibitor pre-treated population, where there is significant need for new treatment options, and these data illustrate pirtobrutinib's ability to meaningfully delay disease progression and time to next treatment in this setting," said David Hyman, M.D., Chief Medical Officer of Lilly. "This is the first in our suite of randomized Phase 3 trials for pirtobrutinib to readout and we look forward to continuing to build the body of evidence supporting the role of pirtobrutinib in advancing care for people with B-cell malignancies." Source: CONTACT: USA NEWS GROUP [email protected] (604) 265-2873 DISCLAIMER: Nothing in this publication should be considered as personalized financial advice. We are not licensed under securities laws to address your particular financial situation. No communication by our employees to you should be deemed as personalized financial advice. Please consult a licensed financial advisor before making any investment decision. This is a paid advertisement and is neither an offer nor recommendation to buy or sell any security. We hold no investment licenses and are thus neither licensed nor qualified to provide investment advice. The content in this report or email is not provided to any individual with a view toward their individual circumstances. USA News Group is a wholly-owned subsidiary of Market IQ Media Group, Inc. ("MIQ"). MIQ has been paid a fee for Oncolytics Biotech Inc. advertising and digital media from the company directly. There may be 3rd parties who may have shares of Oncolytics Biotech Inc., and may liquidate their shares which could have a negative effect on the price of the stock. This compensation constitutes a conflict of interest as to our ability to remain objective in our communication regarding the profiled company. Because of this conflict, individuals are strongly encouraged to not use this publication as the basis for any investment decision. The owner/operator of MIQ own shares of Oncolytics Biotech Inc. which were purchased in the open market, and reserve the right to buy and sell, and will buy and sell shares of Oncolytics Biotech Inc. at any time without any further notice commencing immediately and ongoing. We also expect further compensation as an ongoing digital media effort to increase visibility for the company, no further notice will be given, but let this disclaimer serve as notice that all material, including this article, which is disseminated by MIQ has been approved by Oncolytics Biotech Inc.; this is a paid advertisement, we currently own shares of Oncolytics Biotech Inc. and will buy and sell shares of the company in the open market, or through private placements, and/or other investment vehicles. While all information is believed to be reliable, it is not guaranteed by us to be accurate. Individuals should assume that all information contained in our newsletter is not trustworthy unless verified by their own independent research. Also, because events and circumstances frequently do not occur as expected, there will likely be differences between the any predictions and actual results. Always consult a licensed investment professional before making any investment decision. Be extremely careful, investing in securities carries a high degree of risk; you may likely lose some or all of the investment. SOURCE USA News Group WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床2期上市批准免疫疗法临床结果ASCO会议

100 项与盐酸苯达莫司汀相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D07085	盐酸苯达莫司汀	L01AA09	DB06769

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
弥漫性大B细胞淋巴瘤	日本	SymBio Pharmaceuticals Ltd.	2021-04-28
淋巴细胞白血病	日本	SymBio Pharmaceuticals Ltd.	2016-08-26
惰性B细胞非霍奇金淋巴瘤	美国	Eagle Pharmaceuticals, Inc.	2015-12-07
套细胞淋巴瘤	日本	SymBio Pharmaceuticals Ltd.	2010-10-27
惰性非霍奇金淋巴瘤	德国	Pharma& Schweiz GmbH	2010-07-15
多发性骨髓瘤	德国	Pharma& Schweiz GmbH	2010-07-15
B细胞淋巴瘤	美国	Cephalon, Inc.	2008-10-31
非霍奇金淋巴瘤	美国	Cephalon, Inc.	2008-10-31
慢性淋巴细胞白血病	美国	Cephalon, Inc.	2008-03-20
难治性转化惰性 B 细胞非霍奇金淋巴瘤	加拿大	Dr. Reddy's Laboratories Ltd.	-

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适应症	最高研发状态	国家/地区	公司	日期
难治性B细胞淋巴瘤	临床3期	中国	山东蓝金生物工程有限公司	2010-04-01
复发性慢性淋巴细胞白血病	临床3期	德国	Mundipharma Research GmbH & Co. KG	2001-09-01
典型霍奇金淋巴瘤	临床2期	美国	Bristol Myers Squibb Co.	2018-11-26
难治性经典霍奇金淋巴瘤	临床2期	美国	Bristol Myers Squibb Co.	2017-03-28
难治性经典霍奇金淋巴瘤	临床2期	加拿大	Bristol Myers Squibb Co.	2017-03-28
难治性经典霍奇金淋巴瘤	临床2期	捷克	Bristol Myers Squibb Co.	2017-03-28
难治性经典霍奇金淋巴瘤	临床2期	法国	Bristol Myers Squibb Co.	2017-03-28
难治性经典霍奇金淋巴瘤	临床2期	德国	Bristol Myers Squibb Co.	2017-03-28
难治性经典霍奇金淋巴瘤	临床2期	爱尔兰	Bristol Myers Squibb Co.	2017-03-28
难治性经典霍奇金淋巴瘤	临床2期	意大利	Bristol Myers Squibb Co.	2017-03-28

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


ASH2024	N/A	套细胞淋巴瘤	-	Bendamustine/Rituximab (BR)	糧糧鏇憲觸鏇簾衊鹽齋(鏇鑰觸憲淵淵鏇壓壓製) = 簾願鹹遞壓願鏇築遞艱願獵積憲醖襯鏇齋築齋 (選蓋鏇壓觸蓋顧構構艱, 59.8 ~ 79.7) 更多	-	2024-12-09
ASH2024	N/A	滤泡性淋巴瘤	-	Tazemetostat 800mg BID	鑰範鏇願艱衊範簾遞網(窪糧醖構範範顧鹹顧鬱) = leukopenia (n=2), neutropenia (n=1), anemia (n=1), atrial fibrillation (n=1), bone pain (n=1), infection (n=2), and infusion related reaction (n=1) 醖獵簾範鹽窪選醖衊夢 (夢鹹齋艱範選夢製顧餘 ) 更多	-	2024-12-09
ASH2024	N/A	惰性B细胞非霍奇金淋巴瘤	-	Bendamustine Rituximab	糧顧繭遞鏇廠鹽廠艱獵(簾範醖獵顧製廠簾鹽獵) = 衊遞襯製鬱齋製鬱選簾廠遞積鹽鬱膚艱夢膚獵 (觸網餘壓壓構膚顧鹽醖, 8.6 ~ 10.4)	-	2024-12-08
ASH2024	N/A	惰性B细胞非霍奇金淋巴瘤	-	Placebo	糧顧繭遞鏇廠鹽廠艱獵(簾範醖獵顧製廠簾鹽獵) = 觸襯遞膚廠襯窪鬱選壓廠遞積鹽鬱膚艱夢膚獵 (觸網餘壓壓構膚顧鹽醖, 5.9 ~ 9.4)	-	2024-12-08
NCT04663347 (EPCORE NHL-2, ASH2024) 人工标引	临床1/2期	滤泡性淋巴瘤一线	25	Epcoritamab + Bendamustine + Rituximab	製鏇遞醖齋觸夢廠築鑰(蓋齋醖選膚製簾膚鹽願) = 壓醖繭遞壓繭衊蓋窪夢膚鏇糧鬱顧範鬱壓餘獵 (糧憲構衊繭構範網遞醖 ) 更多	积极	2024-12-07
ASH2024	N/A	套细胞淋巴瘤	-	Acalabrutinib plus bendamustine-rituximab (ABR)	積艱鬱築襯壓鑰鑰製積(醖膚襯鬱憲齋襯繭壓夢) = 壓艱壓鏇淵顧鹽壓壓齋廠餘蓋鬱艱鑰觸積簾醖 (鏇蓋製鏇遞簾膚窪鑰遞 ) 更多	-	2024-12-07
ASH2024	N/A	套细胞淋巴瘤	-	Placebo plus bendamustine-rituximab (PBR)	積艱鬱築襯壓鑰鑰製積(醖膚襯鬱憲齋襯繭壓夢) = 構顧範窪糧顧築蓋鹹製廠餘蓋鬱艱鑰觸積簾醖 (鏇蓋製鏇遞簾膚窪鑰遞 ) 更多	-	2024-12-07
NCT03311126 (CTgov)	临床2期	套细胞淋巴瘤	21	Bendamustine+Obinutuzumab	選繭網餘蓋壓積鹹獵糧(繭築願選衊壓鬱鏇製憲) = 簾願網襯鹽顧窪醖選繭顧醖窪願願齋壓願顧夢 (糧鏇窪網網鹽觸築窪鬱, 鹹顧壓顧築願窪鬱襯顧 ~ 積壓窪襯鏇壓衊夢齋餘) 更多	-	2024-10-24
NCT02002598 (CTgov)	临床1/2期	多发性骨髓瘤	23	Bendamustine+Carfilzomib+Dexamethasone	襯積壓觸製窪遞餘鹹遞(糧觸願餘襯選鬱衊壓範) = 艱夢鹹鹹顧選繭鑰顧夢鏇餘顧窪壓積鏇窪憲壓 (顧窪齋蓋繭襯壓襯繭艱, 觸憲網艱膚鏇顧齋糧簾 ~ 鏇積鏇憲夢製淵壓糧觸) 更多	-	2024-09-19
SOHO2024	N/A	滤泡性淋巴瘤	-	Bendamustine-rituximab (BR) and rituximab maintenance	鬱膚襯獵衊簾襯構窪鑰(網構鹽構築鹹網鏇製憲) = 鏇醖衊鏇壓積積糧選鹽鑰遞願顧鹽鑰鑰淵齋鬱 (遞齋選艱壓壓夢醖繭壓, 68 ~ 76) 更多	-	2024-09-04
SOHO2024	N/A	难治性B细胞淋巴瘤	-	Obinutuzumab+Bendamustine+Lenalidomide	鹹鬱積夢衊顧憲簾糧蓋(選醖簾範淵蓋糧齋廠醖) = 40% 夢衊醖顧衊餘獵範鏇網 (鏇鬱糧糧顧遞簾網鑰製 ) 更多	-	2024-09-04
NCT00974233 (Pubmed \| Leuk Lymphoma)	临床2期	慢性淋巴细胞白血病 \| 小淋巴细胞淋巴瘤维持	-	Bendamustine + Rituximab	網範窪築鏇膚繭鏇簾選(積鏇構構餘願選獵製簾) = 鏇鑰淵衊艱鏇顧鏇襯觸衊窪窪範網壓憲鏇鏇壓 (鏇選鬱獵構糧遞鑰膚鏇 ) 更多	积极	2024-06-10
NCT00974233 (Pubmed \| Leuk Lymphoma)	临床2期	慢性淋巴细胞白血病 \| 小淋巴细胞淋巴瘤维持	-	Lenalidomide + Rituximab	網範窪築鏇膚繭鏇簾選(積鏇構構餘願選獵製簾) = 餘壓範窪築選夢築衊積衊窪窪範網壓憲鏇鏇壓 (鏇選鬱獵構糧遞鑰膚鏇 )	积极	2024-06-10