Phase 1/2 Multi-Center Study to Evaluate the Safety and Efficacy of ONCT-808 in Adult Subjects With Relapsed or Refractory Aggressive B-Cell Malignancies

This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy, ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies.

开始日期2023-05-09

申办/合作机构

Oncternal Therapeutics, Inc.

100 项与 ROR1 CAR-T (Oncternal Therapeutics) 相关的临床结果

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100 项与 ROR1 CAR-T (Oncternal Therapeutics) 相关的转化医学

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100 项与 ROR1 CAR-T (Oncternal Therapeutics) 相关的专利（医药）

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项与 ROR1 CAR-T (Oncternal Therapeutics) 相关的文献（医药）

2024-04-01·Journal for immunotherapy of cancer

Armored TGFβRIIDN ROR1-CAR T cells reject solid tumors and resist suppression by constitutively-expressed and treatment-induced TGFβ1

Article

作者: Tran, Ngoc Q ; Chand Thakuri, Bal Krishna ; Dash, Pradyot ; Schneider, Dina ; Lee, Jia-Jye ; Hu, Peirong ; Steimle, Brittany ; Tran, Tri Minh ; Nurmukhambetova, Saule

Background:

Chimeric antigen receptor (CAR) T-cell therapy target receptor tyrosine kinase-like orphan receptor 1 (ROR1) is broadly expressed in hematologic and solid tumors, however clinically-characterized ROR1-CAR T cells with single chain variable fragment (scFv)-R12 targeting domain failed to induce durable remissions, in part due to the immunosuppressive tumor microenvironment (TME). Herein, we describe the development of an improved ROR1-CAR with a novel, fully human scFv9 targeting domain, and augmented with TGFβRIIDN armor protective against a major TME factor, transforming growth factor beta (TGFβ).

Methods:

CAR T cells were generated by lentiviral transduction of enriched CD4+and CD8+T cells, and the novel scFv9-based ROR1-CAR-1 was compared with the clinically-characterized ROR1-R12-scFv-based CAR-2 in vitro and in vivo.

Results:

CAR-1 T cells exhibited greater CAR surface density than CAR-2 when normalized for %CAR+, and produced more interferon (IFN)-γ tumor necrosis factor (TNF)-α and interleukin (IL)-2 in response to hematologic (Jeko-1, RPMI-8226) and solid (OVCAR-3, Capan-2, NCI-H226) tumor cell lines in vitro. In vivo, CAR-1 and CAR-2 both cleared hematologic Jeko-1 lymphoma xenografts, however only CAR-1 fully rejected ovarian solid OVCAR-3 tumors, concordantly with greater expansion of CD8+and CD4+CAR T cells, and enrichment for central and effector memory phenotype. When equipped with TGFβ-protective armor TGFβRIIDN, CAR-1 T cells resisted TGFβ-mediated pSmad2/3 phosphorylation, as compared with CAR-1 alone. When co-cultured with ROR-1+AsPC-1 pancreatic cancer line in the presence of TGFβ1, armored CAR-1 demonstrated improved recovery of killing function, IFN-γ, TNF-α and IL-2 secretion. In mouse AsPC-1 pancreatic tumor xenografts overexpressing TGFβ1, armored CAR-1, in contrast to CAR-1 alone, achieved complete tumor remissions, and yielded accelerated expansion of CAR+T cells, diminished circulating active TGFβ1, and no apparent toxicity or weight loss. Unexpectedly, in AsPC-1 xenografts without TGFβ overexpression, TGFβ1 production was specifically induced by ROR-1-CAR T cells interaction with ROR-1 positive tumor cells, and the TGFβRIIDN armor conferred accelerated tumor clearance.

Conclusions:

The novel fully human TGFßRIIDN-armored ROR1-CAR-1 T cells are highly potent against ROR1-positive tumors, and withstand the inhibitory effects of TGFß in solid TME. Moreover, TGFβ1 induction represents a novel, CAR-induced checkpoint in the solid TME, which can be circumvented by co-expressing the TGβRIIDN armor on T cells.

2022-12-01·Breast cancer research : BCR

Inducible localized delivery of an anti-PD-1 scFv enhances anti-tumor activity of ROR1 CAR-T cells in TNBC

Article

作者: Muczynski, Vincent ; Della Peruta, Marco ; Nathwani, Amit Chunilal ; Patel, Dominic ; Lau, Hiu ; Miranda, Elena ; Gohil, Satyen Harish ; Evans, Rachel ; Granger, David ; Harrasser, Micaela ; Grigoriadis, Kristiana ; Grigoriadis, Anita

Abstract:

Background:

Chimeric antigen receptor (CAR)-T cells can induce powerful immune responses in patients with hematological malignancies but have had limited success against solid tumors. This is in part due to the immunosuppressive tumor microenvironment (TME) which limits the activity of tumor-infiltrating lymphocytes (TILs) including CAR-T cells. We have developed a next-generation armored CAR (F i-CAR) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), which is expressed at high levels in a range of aggressive tumors including poorly prognostic triple-negative breast cancer (TNBC). The F i-CAR-T is designed to release an anti-PD-1 checkpoint inhibitor upon CAR-T cell activation within the TME, facilitating activation of CAR-T cells and TILs while limiting toxicity.

Methods:

To bolster potency, we developed a F i-CAR construct capable of IL-2-mediated, NFAT-induced secretion of anti-PD-1 single-chain variable fragments (scFv) within the tumor microenvironment, following ROR1-mediated activation. Cytotoxic responses against TNBC cell lines as well as levels and binding functionality of released payload were analyzed in vitro by ELISA and flow cytometry. In vivo assessment of potency of F i-CAR-T cells was performed in a TNBC NSG mouse model.

Results:

F i-CAR-T cells released measurable levels of anti-PD-1 payload with 5 h of binding to ROR1 on tumor and enhanced the cytotoxic effects at challenging 1:10 E:T ratios. Treatment of established PDL1 + TNBC xenograft model with F i-CAR-T cells resulted in significant abrogation in tumor growth and improved survival of mice (71 days), compared to non-armored CAR cells targeting ROR1 (F CAR-T) alone (49 days) or in combination with systemically administered anti-PD-1 antibody (57 days). Crucially, a threefold increase in tumor-infiltrating T cells was observed with F i-CAR-T cells and was associated with increased expression of genes related to cytotoxicity, migration and proliferation.

Conclusions:

Our next-generation of ROR1-targeting inducible armored CAR platform enables the release of an immune stimulating payload only in the presence of target tumor cells, enhancing the therapeutic activity of the CAR-T cells. This technology provided a significant survival advantage in TNBC xenograft models. This coupled with its potential safety attributes merits further clinical evaluation of this approach in TNBC patients.

2021-02-01·Cancer cell1区 · 医学

Immunogenic Chemotherapy Enhances Recruitment of CAR-T Cells to Lung Tumors and Improves Antitumor Efficacy when Combined with Checkpoint Blockade

1区 · 医学

Article

作者: Sarah M. Garrison ; Valentin Voillet ; Christoph Rader ; Sushma Yechan-Gunja ; Robert H. Pierce ; Smitha P.S. Pillai ; Vishaka Muhunthan ; Jennifer M. Specht ; Carolina Berger ; A. McGarry Houghton ; Kimberly S. Smythe ; Robert A. Amezquita ; David G. Maloney ; Megha Sarvothama ; Scott N. Furlan ; Carla A. Jaeger-Ruckstuhl ; Shivani Srivastava ; Raphael Gottardo ; Stanley R. Riddell ; Sylvia M. Lee

Adoptive therapy using chimeric antigen receptor-modified T cells (CAR-T cells) is effective in hematologic but not epithelial malignancies, which cause the greatest mortality. In breast and lung cancer patients, CAR-T cells targeting the tumor-associated antigen receptor tyrosine kinase-like orphan receptor 1 (ROR1) infiltrate tumors poorly and become dysfunctional. To test strategies for enhancing efficacy, we adapted the Kras^LSL-G12D/+;p53^f/f autochthonous model of lung adenocarcinoma to express the CAR target ROR1. Murine ROR1 CAR-T cells transferred after lymphodepletion with cyclophosphamide (Cy) transiently control tumor growth but infiltrate tumors poorly and lose function, similar to what is seen in patients. Adding oxaliplatin (Ox) to the lymphodepletion regimen activates tumor macrophages to express T-cell-recruiting chemokines, resulting in improved CAR-T cell infiltration, remodeling of the tumor microenvironment, and increased tumor sensitivity to anti-PD-L1. Combination therapy with Ox/Cy and anti-PD-L1 synergistically improves CAR-T cell-mediated tumor control and survival, providing a strategy to improve CAR-T cell efficacy in the clinic.

项与 ROR1 CAR-T (Oncternal Therapeutics) 相关的新闻（医药）

2024-12-11

·生物制药小编

危险的靶点，100%的CR

近日，默沙东公布了其ROR1—ADC药物zilovertamab vedotin+R-CHP作为弥漫性大b细胞淋巴瘤（DLBCL）一线治疗方案的Ⅱ期临床初步数据—wavine -007，结果显示，该联合方案在两个剂量组中均实现了100%的完全缓解。一位BMO Capital Markets分析师称，数据非常有竞争力，但未来安全性是个问题。疗效惊艳，安全可疑 Zilovertamab vedotin是一款靶向ROR1—ADC，是默沙东2020年收购VelosBio公司获得的资产，该试验评估了不同剂量zilovertamab vedotin联合R-CHP用以未经治疗DLBCL患者的安全性与有效性。共有36名患者入组，中位随访时间为17.6个月。试验结果显示，1.75mg/kg和2.25mg/kg剂量组的CR分别为100%，2.0mg/kg的CR略低，为93.3% 。截至数据统计时，全部患者还未达到中位缓解持续时间（DOR）。基于该结果，默沙东将1.75mg/kg作为zilovertamab vedotin的III期临床的推荐剂量。 Zilovertamab vedotin取得高CR率的另一面是令人担忧的安全性问题。该项临床中，有58%的患者出现3-4级治疗相关不良事件，11%的患者出现了严重的治疗相关不良事件，1.75mg/kg组所有患者均完成了治疗，而2.25mg/kg和2.0mg/kg剂量组分别有1例患者停药。从目前的响应率来看，zilovertamab vedotin的疗效还是非常惊艳，不过鉴于患者样本量较少，在更大规模的Ⅲ期临床中能不能维持这样的响应以及不良事件是否会升级仍值得关注。两款CAR-T的失足 ROR1是一种典型的肿瘤胚胎蛋白，通常只存在于胚胎细胞的早期发育阶段，而在成体细胞中一般不表达，但是它被癌细胞利用后会促进癌细胞的生长和扩散。目前ROR1已被发现在多种肿瘤中高表达，包括各类白血病、非霍奇金淋巴瘤、乳腺癌、肺癌及卵巢癌。有介于这种在肿瘤和正常组织之间的高度差异化表达，ROR1成为一种潜力靶点。围绕ROR1的开发汇集了CAR-T，双抗/多抗，ADC等多种技术路线。 ROR1作为ADC的一种潜力开发靶点被广泛注意到是在2020年，基石药业、默沙东、勃林格殷格翰先后通过授权/并购获得ROR1 ADC药物的相关权益。整体来看，最快的是Oncternal公司ROR1单抗Zilovertamab，进入Ⅲ期临床阶段。根据已披露的的Ⅰ/Ⅱ期临床，表达P53突变/del(17p)的CLL患者获得100%的无进展生存期（PFS），持续48个月。但是在2023年4月，Oncternal取消了Zilovertamab的优先级，关闭了其针对MCL的Ⅲ期临床和Ⅰ/Ⅱ期临床。目前已有ROR1靶向药的临床数据公布有限，就已经已有的临床数据来看，ROR1是一个安全风险比较高的靶点，两款ROR1 CAR-T皆因此折戟。 2024年6月，Lyell的ROR1 CAR-T疗法LYL797在三阴乳腺癌（TNBC）的I期临床报告了发生了一例死亡事件，还有22%的患者出现肺炎相关的剂量限制毒性，最常见的严重程度为3级或更高。4个月后，Lyell便宣布停止对LYL797的开发。Lyell的首席执行官Lynn Seely在电话会议上表示，LYL797遇到了安全问题，并且没有足够的治疗窗口。无独有偶，另一家ROR1开发公司Oncternal也报告了ROR1 CAR-T（ONCT-808）临床发生死亡案例，并且还预期ONCT-808治疗会发生不良事件。ONCT-808的临床开发已经停止，该公司正在考虑战略替代方案。参考出处 https://www.biospace.com/drug-development/merck-touts-100-complete-response-rate-for-anti-ror1-adc-as-first-line-lymphoma-treatment https://www-merck-com.libproxy1.nus.edu.sg/news/mercks-investigational-zilovertamab-vedotin-in-combination-with-r-chp-demonstrates-complete-response-rate-of-100-at-1-75-mg-kg-dose-in-phase-2-trial-of-previously-untreated-patients-with-diff/

抗体药物偶联物免疫疗法细胞疗法临床2期临床结果

2024-10-28

·佰傲谷BioValley

核心管线挣扎无效，不详的ROR1

ROR1 CAR-T细胞疗法LYL797，在报告了临床死亡事件后，研发公司Lyell Immunopharma努力挣扎了4个月后，最终还是宣布停止对其的开发。又一领先的ROR1 CAR-T管线停止，预示着ROR1靶点的不详。患者死亡事件 2024年6月，Lyell报告了LYL797在三阴乳腺癌（TNBC）的I期临床中发生了一例死亡事件。延伸阅读：实体瘤CAR-T患者死亡，股价跌去36% LYL797是一款基于Lyell公司专有的Gen-R技术平台开发的ROR1靶向CAR-T细胞，经过体外重编程使T细胞过表达蛋白质c-JUN，从而实现延缓衰竭并保持抗肿瘤功能。在一项针对三阴乳腺癌的I期临床中，一名患者在第41天出现5级呼吸衰竭后死亡。此外，22%的患者中出现肺炎相关的剂量限制毒性，最常见的严重程度为3级或更高。出现死亡事件的可能原因是ROR1靶点。虽然ROR1在正常的肺部细胞中几乎不表达，但是在一些肺癌中呈现出异常高表达，而考虑到乳腺癌的特殊位置，一些患者实际上已经出现了乳腺癌的肺转移情况，这也使得一些患者出现肺部受累的情况。 LYL797挣扎无效实际上，LYL797的这例死亡事件并没有引起美国FDA的警惕，临床并未暂停。Lyell公司仅是对临床进行了调整。 Lyell公司在2024年8月发布的第二季度财报中，还报告了LYL797的临床开发计划，包括针对三阴性乳腺癌（TNBC）或非小细胞肺癌（NSCLC）的临床继续进行，扩大标签至卵巢癌和子宫内膜癌，以及下半年提交针对多发性骨髓瘤和慢性淋巴细胞白血病的第二个IND。很明显，死亡事件一开始并未打击到Lyell公司对于LYL797的信心。同时，该公司以TNBC研究的最高剂量队列中，40%的客观缓解率和60%的临床获益率，作为宣传的主要数据。然后，期间不知道发生了什么，在距第二季度财报发布2个月多后，Lyell公司突然宣布要停止对LYL797的开发工作。 Lyell公司的首席执行官Lynn Seely在电话会议上，表明LYL797遇到了安全问题，并且没有“足够广泛的治疗窗口”。另外，同时被放弃的还包括LYL845在内的TIL项目，停止LYL845的原因很明确，因为临床数据不符合持续开发的预期标准，导致其他TIL项目也一同被放弃了。仍然死磕ROR1 小编猜测，LYL797的安全问题主要还是归因于，ROR1靶点比较难把控。无独有偶，另一家ROR1开发公司Oncternal也报告了ROR1 CAR-T（ONCT-808）临床发生了死亡案例，同时预期ONCT-808治疗会发生不良事件。ONCT-808的临床已经停止，同时该公司现在正在考虑战略代替方案....... 延伸阅读： 2个核心管线同时暴雷，首席医疗官出走 ROR1 CAR-T：临床数据出炉但是，ROR1开发难度高也不好使。在LYL797失败后，Lyell公司仍然在死磕ROR1 CAR-T。因为Lyell公司在管线重组以后，新的核心管线赫然是以LYL797为基础开发的下一代的ROR1 CAR-T疗法LYL119。Lyell公司表示，LYL119能够在更低剂量下产生更好的疗效，并具有更广泛的治疗窗口。 ROR1 CAR-T的下一代产品LYL119在c-JUN过表达的基础上还增添了多项技术，例如敲除NR4A3基因进一步减少T细胞凋亡和衰竭，采用Stim-R™技术来强化信号转导，采用该公司的Epi-R™技术生产具有持久干细胞特性的T细胞。最后在本身的技术之外，还结合了来自哈佛大学Wyss研究所的T细胞增强支架技术来强化临床获益，这种技术提供了一种能够模拟人体淋巴系统的支架材料，这种支架材料可以携带激活CAR-T需要的IL-2以及CAR-T上的CD3受体和CD28受体。目前，该公司已经完成了LYL119的IND提交，预计将于今年或明年初启动针对铂类耐药卵巢癌或复发/难治性子宫内膜癌的1期临床。 CD19/CD20 CAR-T也挺香另一个好消息是，Lyell公司也没有头铁到眼里只有ROR1。在自身管线或是因为安全性、或是因为疗效被放弃，只剩下一根独苗LYL119后，Lyell公司将目光放到了外部，瞄准了一家小型CAR-T研发公司ImmPACT Bio，并以3000万美元现金和3750万股Lyell普通股对ImmPACT Bio进行收购。被Lyell公司看中的是ImmPACT管线内一款CD19/CD20 CAR-T细胞候选产品IMPT-314。ImmPACT的其他管线（包括Claudin 18.2 CAR-T）优先级并不高。 IMPT-314是一款自体的、CD19/CD20双特异性CAR-T细胞，被开发用于治疗B细胞淋巴瘤和自身免疫性疾病。Lyell公司将优先开发IMPT-314的B细胞淋巴瘤适应症。 IMPT-314目前正在进行临床研究，预计将于今年晚些时候发布IMPT-314针对大B细胞淋巴瘤的临床数据。IMPT-314的关键试验预计将于2025年启动。根据Lyell公司第二季度财报，截止2024年6月30日，拥有现金、现金等价物和有价证券4.911亿美元。尽管收购ImmPACT需要花费一定现金，但是Lyell公司删减了管线的开发工作，仅剩2条临床管线，这使得Lyell公司的现金流支持公司运营至2027年。小结虽然但是，Lyell公司一口气停了好几个内部管线的开发，包括LYL797和全部的TIL项目，还是令人对其的研发实力产生质疑。这一点也反应到了股市上，Lyell公司的股票持续下跌，截止本文发布前，已经跌至1美元以下，报9.27美分/股。参考资料： 1.https://ir.lyell.com/news-releases/news-release-details/lyell-immunopharma-acquire-immpact-bio-and-prioritizes-its 2.https://ir.lyell.com/news-releases/news-release-details/lyell-immunopharma-reports-business-highlights-and-financial-5 本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

免疫疗法财报临床1期细胞疗法临床申请

2024-10-25

·GlobeNewswire-Health Care

Oncternal Therapeutics Announces Updated Safety and Efficacy Data for Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer

Oct. 22, 2024 -- Oncternal Therapeutics, Inc. (Nasdaq: ONCT) (the “Company”) today announced updated data from its Phase 1/2 Study of ONCT-534 for the treatment of patients with relapsed or refractory metastatic Castration-Resistant Prostate Cancer (mCRPC). Based on initial pharmacokinetic results, two additional dosing cohorts with twice daily (BID) oral dosing of ONCT-534 had been incorporated in the Phase 1/2 study ONCT-534-101 (NCT05917470). Overall, fifteen patients received ONCT-534 once daily (QD) in six dosing cohorts and six patients received ONCT-534 BID in two dosing cohorts. Based on a data cut off of September 30, 2024, the BID dosing schedule was well tolerated, with no related Grade 3 or higher toxicities. One patient, who experienced a rising PSA on ONCT-534 at 160 mg BID, had a subsequent 50% reduction in PSA after four weeks of ONCT-534 at 300 mg BID, and at the same time the CAT Scan showed a 16% reduction in target lesions compared to baseline. Enumeration and biomarker analysis of circulating tumor cells (CTCs) showed promising effects on expression of androgen receptor (AR)-regulated genes, and AR nuclear translocation in six additional patients. CTC analysis also showed that some patients who did not respond to ONCT-534 had prostate cancer that had developed neuroendocrine features, which are associated with AR independent disease. “While we still believe the decision to discontinue the ONCT-534-101 clinical trial remains the correct one in the current biotechnology environment, the updated clinical results highlight the potential of ONCT-534 in prostate cancer. We believe there is value in exploring BID dosing further, as well as studying ONCT-534 in earlier lines of therapy for advanced prostate cancer,” said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. “We continue to explore strategic alternatives for our product candidates, including ONCT-534, ONCT-808, zilovertamab and ONCT-216 in an ongoing effort to maximize value to our shareholders.” Oncternal Therapeutics is a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies for the treatment of patients with cancers that have critical unmet medical need. Oncternal pursues drug development targeting promising, yet untapped biological pathways implicated in cancer generation or progression, focusing on hematological malignancies and prostate cancer. More information on our company and programs is available at https://oncternal.com/. ONCT-534 is an investigational dual-action androgen receptor inhibitor (DAARI) with demonstrated preclinical activity in prostate cancer models against both unmutated androgen receptor (AR), and against multiple forms of AR mutation and aberration. It is a potential treatment for patients with mCRPC with unmet medical need because of resistance to androgen receptor pathway inhibitors, including those with AR amplification, mutations in the AR ligand binding domain (LBD), or splice variants with loss of the AR LBD. It was investigated in Study ONCT-534-101 (NCT05917470) for the treatment of patients with mCRPC who are resistant to current AR pathway inhibitors. ONCT-808 is an investigational autologous chimeric antigen receptor T (CAR T) cell therapy that targets Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using the binding domain from zilovertamab. ONCT-808 has demonstrated activity in preclinical models against multiple hematological malignancies and solid tumors and has been shown to be specific for cancer cells expressing ROR1. Oncternal has developed a robust and reproducible manufacturing process that has the potential to reduce the time patients must wait for their individual CAR T therapy to be produced compared with currently approved CAR T products. It was investigated in Study ONCT-808-101 (NCT05588440) with relapsed or refractory aggressive B-cell lymphoma, including patients who have failed previous CD19 CAR T treatment. Zilovertamab (previously called cirmtuzumab and UC-961) is an investigational monoclonal antibody designed to inhibit the function of Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1). Zilovertamab has been evaluated in Phase 1/2 Study CIRM-0001 (NCT03088878) in combination with ibrutinib for the treatment of patients with mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL) and marginal zone lymphoma (MZL), which resulted in 100% progression free survival (PFS) at 48 months in CLL patients whose tumors harbored del(17p)/p53 mutation, a population underserved by current treatment options. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to zilovertamab for the treatment of CLL and MCL. The results of an investigator-sponsored, Phase 1b clinical trial of zilovertamab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced, unresectable breast cancer were recently published (Shatsky 2023). Zilovertamab was evaluated in an investigator-initiated Phase 1b study of zilovertamab in combination with docetaxel in patients with metastatic castration-resistant prostate cancer (NCT05156905), and an investigator-initiated Phase 2 clinical trial of zilovertamab in combination with venetoclax, a Bcl-2 inhibitor, in patients with relapsed/refractory (R/R) CLL (NCT04501939). ONCT-216 (previously called TK216) is an investigational targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as acute myeloid leukemia (AML), diffuse large B cell lymphoma (DLBCL), and prostate cancer. In preclinical models, ONCT-216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease Designation, Orphan Drug Designation and Fast Track Status to ONCT-216 for the treatment of Ewing sarcoma. The results of a Phase 1/ 2 clinical trial of ONCT-216 in patients with Ewing sarcoma (NCT02657005) were recently published (Myers 2024). The content above comes from the network. if any infringement, please contact us to modify.

临床结果孤儿药快速通道免疫疗法

100 项与 ROR1 CAR-T (Oncternal Therapeutics) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
B细胞恶性肿瘤	临床2期	美国	Oncternal Therapeutics, Inc.	2023-05-09
非霍奇金淋巴瘤	临床2期	美国	Oncternal Therapeutics, Inc.	2022-10-05
血液肿瘤	临床前	-	Oncternal Therapeutics, Inc.	-
实体瘤	临床前	-	Oncternal Therapeutics, Inc.	-

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临床结果

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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


NCT05588440 (ONCT-808-101, CTgov)	临床1/2期	B细胞恶性肿瘤	9	CAR T Cells+ONCT-808 (ONCT-808 1x10^6 CAR T Cells/kg)	餘顧淵製糧選壓築獵鏇(廠築醖齋觸鏇淵齋鹹願) = 憲鏇艱積構鏇觸網齋憲範壓積壓窪鏇醖鬱廠獵 (鏇遞遞遞餘艱網齋鹽構, 廠鏇廠鑰襯範壓獵遞衊 ~ 襯廠蓋齋糧顧夢選蓋鏇) 更多	-	2024-12-05
NCT05588440 (ONCT-808-101, CTgov)	临床1/2期	B细胞恶性肿瘤	9	CAR T Cells+ONCT-808 (ONCT-808 3x10^6 CAR T Cells/kg)	餘顧淵製糧選壓築獵鏇(廠築醖齋觸鏇淵齋鹹願) = 醖顧鬱膚膚遞獵糧齋齋範壓積壓窪鏇醖鬱廠獵 (鏇遞遞遞餘艱網齋鹽構, 鑰繭醖築鹽蓋夢齋範繭 ~ 繭壓壓選築遞製繭願夢) 更多	-	2024-12-05
NCT05588440 (ONCT-808-101, Corporate Publications) 人工标引	临床1/2期	侵袭性 B 细胞非霍奇金淋巴瘤	3	ONCT-808	獵鏇窪築憲憲鏇鏇鏇鹹(觸鹹鹹膚壓壓鹹餘醖鹽) = included decreased blood counts, pneumonia and Grade 1-2 cytokine release syndrome (CRS) as of a 4 December 2023 data cutoff 願膚醖蓋繭襯餘繭憲鹽 (蓋鹹糧艱鏇鹽餘顧艱憲 )	积极	2023-12-26
SITC2023	N/A	ROR1	-	ONCT-808	餘淵積製繭夢憲齋顧鑰(壓網衊淵鹽鑰醖膚網糧) = 繭壓淵簾窪製鹽獵壓獵鏇願簾壓糧齋獵憲簾製 (醖餘壓衊選夢網獵觸夢 )	积极	2023-11-02