A Phase II Study With a Safety Run-In of the Addition of N-803, a Novel IL-15 Super-Agonist, to a Chemoimmunotherapy Backbone for the Treatment of Patients With Relapsed or Refractory Neuroblastoma

The study participant is being asked to take part in this research study because the participant has been diagnosed with neuroblastoma that did not fully respond to previous treatment (refractory), or it has returned after treatment (relapsed).
Primary Aims
* To evaluate if the administration of N-803 in combination with irinotecan, temozolomide, hu14-18K322A, and GM-CSF in patients with relapsed/refractory neuroblastoma is feasible and tolerable
* To determine if the response rate of N-803 with irinotecan, temozolomide, hu14.18K322A and GM-CSF in patients with relapsed/refractory neuroblastoma is superior to the combination of irinotecan, temozolomide, hu14.18K322A, and GM-CSF
Secondary Aims
* To describe the toxicity profile of N-803 administered with irinotecan, temozolomide, hu14.18K322A and GM-CSF
* To evaluate and compare the progression free survival (PFS) and overall survival (OS) of and between patients receiving irinotecan, temozolomide, hu14.18K322A and GM-CSF with and without N-803

开始日期2025-11-10

申办/合作机构

St. Jude Children's Research Hospital, Inc.

NCT02130869

/ Completed临床1期IIT

A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas

This is a pilot clinical trial investigating the addition of haploidentical natural killer cell infusion to autologous stem cell transplantation. This intervention will be evaluated in children with high-risk solid tumors for whom autologous transplantation is indicated. Natural killer cells from a haploidentical family member will be given after high dose chemotherapy and positively selected autologous stem cells. In patients with neuroblastoma, the anti-GD2 antibody hu14.18K322A will also be given. The effect on normal hematopoietic cell recovery will be evaluated and survival of children treated with this approach will be determined.
The investigators expect to enroll 36 participants. Haploidentical family members (donors) will also be recruited to provide natural killer cells.

开始日期2014-10-10

申办/合作机构

St. Jude Children's Research Hospital, Inc.

NCT01857934

/ Completed临床2期IIT

Neuroblastoma Protocol 2012: Therapy for Children With Advanced Stage High-Risk Neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in childhood, with nearly 50% of patients presenting with widespread metastatic disease. The current treatment for this group of high-risk patients includes intensive multi-agent chemotherapy (induction) followed by myeloablative therapy with stem-cell rescue (consolidation) and then treatment of minimal residual disease (MRD) with isotretinoin. Recently a new standard of care was established by enhancing the treatment of MRD with the addition of a monoclonal antibody (ch14.18) which targets a tumor-associated antigen, the disialoganglioside GD2, which is uniformly expressed by neuroblasts. Despite improvement in 2-year event-free survival (EFS) of 20%, more than one-third of children with high-risk neuroblastoma (HR defined in) still cannot be cured by this approach. Therefore, novel therapeutic approaches are needed for this subset of patients. This study will be a pilot Phase II study of a unique anti-disialoganglioside (anti-GD2) monoclonal antibody (mAb) called hu14.18K322A, given with induction chemotherapy.
PRIMARY OBJECTIVE:
* To study the efficacy [response: complete remission + partial remission (CR+PR)] to two initial courses of cyclophosphamide and topotecan combined with hu14.18K322A (4 doses/course followed by GM-CSF) in previously untreated children with high-risk neuroblastoma.
* To estimate the event-free survival of patients with newly diagnosed high-risk neuroblastoma treated with the addition of hu14.18K322A to treatment.
SECONDARY OBJECTIVES:
* To study the feasibility of delivering hu14.18K322A to 6 cycles induction chemotherapy and describe the antitumor activity (CR+PR) of this 6 course induction therapy.
* To estimate local control and pattern of failure associated with focal intensity modulated or proton beam radiation therapy dose delivery in high-risk abdominal neuroblastoma.
* To describe the tolerability of four doses of hu14.18K322A with allogeneic natural killer (NK) cells from an acceptable parent, in the immediate post-transplant period [day +2 - +5 after peripheral blood stem cell (PBSC) infusion] in consenting participants.
* To describe the tolerability of hu14.18K322A with interleukin-2 and GM-CSF as treatment for minimal residual disease (MRD).

开始日期2013-07-05

申办/合作机构

St. Jude Children's Research Hospital, Inc.

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项与 Daretabart 相关的文献（医药）

2026-01-21·BIOCONJUGATE CHEMISTRY

Utilization of Neutrophil Elastase Tetrapeptide Substrate as a Linker Agent for Anti-GD2 Antibody Drug Conjugates

Article

作者: Zhang, Junyi ; Zheng, Yanbo ; Gong, Jianhua ; Zheng, Yijia ; Gao, Lingli ; Yang, Jigang ; Zhang, Jiajia ; Wei, Hanrui

Disialoganglioside GD2 (GD2) is highly expressed in several tumors. While anti-GD2 antibodies and GD2-based antibody-drug conjugates (ADCs) have shown some therapeutic efficacy, their activity requires enhancement. Elastase, abundant in tumor microenvironment, has substrates that can serve as ADC linkers. Here, we constructed an anti-GD2 ADC by conjugating the anti-GD2 antibody Hu3F8 to the payload monomethyl auristatin E (MMAE) via an elastase-cleavable tetrapeptide linker (BMOA). Hu3F8 was produced using a 293F expression system, and its specific binding to GD2-positive cells was confirmed. The cytotoxicity of the ADCs was evaluated in both GD2-positive and GD2-negative tumor cell lines with or without elastase and its antitumor effects were investigated. It showed GD2-dependent cytotoxicity, with a significantly decreased IC₅₀ in GD2-positive cells upon elastase addition, while no cytotoxicity was observed in GD2-negative cells. Additionally, Hu3F8-BMOA-MMAE induced significant cell cycle arrest and apoptosis in GD2-positive cells, with stronger effects in the presence of elastase. In M21 melanoma mouse models, Hu3F8-BMOA-MMAE achieved an obvious tumor inhibition rate compared to the control. These findings demonstrate that utilizing a neutrophil elastase tetrapeptide substrate as a linker in anti-GD2 ADCs is a potential strategy for the therapy of GD2-positive tumors.

2025-08-20·BIOCONJUGATE CHEMISTRY

ImmunoPET Demonstrates that Co-Targeting GD2 and B7–H3 with Bispecific Antibodies Enhances Tumor Selectivity in Preclinical Melanoma Models

Article

作者: Erbe, Amy K. ; Medina-Guevara, Yadira ; Clemons, Nathan B. ; Hernandez, Reinier ; Sondel, Paul M. ; Engle, Jonathan W. ; Barnhart, Todd E. ; Jeffery, Justin J. ; Rosenkrans, Zachary T. ; Feils, Arika S.

Disialoganglioside 2 (GD2) is overexpressed in multiple cancers, such as melanoma and neuroblastoma, but also in peripheral nerves. To improve current GD2-targeting approaches, next-generation heterodimeric bispecific human IgG antibodies were created, each with one antibody binding fragment (Fab) arm specific for GD2 and the other Fab arm specific for B7-H3 (CD276) to drive tumor selectivity. The avidity and selectivity of our GD2-B7-H3 targeting bispecific antibodies (INV34-6, INV33-2, and INV36-6) were determined by flow cytometry and competition binding assays in GD2⁺/hB7-H3⁺ B78 cells. INV34-6 showed high avidity for GD2⁺/hB7-H3⁺ but not GD2⁺/hB7-H3^- B78 cells, contrasting with the similar cell binding to these cells observed with the anti-GD2 antibody Dinutuximab (DINU). The bispecific antibodies, DINU, and a nontargeted bispecific control (bsAb CTRL) were conjugated with deferoxamine for radiolabeling with Zr-89 (t_1/2 = 78.4 h). Positron emission tomography (PET) corroborated the in vivo avidity and selectivity of the GD2-B7-H3 targeting bispecific compared to bsAb CTRL and DINU in GD2⁺/hB7-H3⁺ and GD2⁺/hB7-H3^- B78 tumor models. PET in mice bearing the GD2⁺/hB7-H3^- and GD2⁺/hB7-H3⁺ B78 murine xenografts showed similar biodistribution in normal tissues for [⁸⁹Zr]Zr-Df-INV34-6, [⁸⁹Zr]Zr-Df-bsAb CTRL, and [⁸⁹Zr]Zr-Df-DINU. Importantly, [⁸⁹Zr]Zr-Df-INV34-6 tumor uptake was selective to GD2⁺/hB7-H3⁺ B78 over GD2⁺/hB7-H3^- B78 tumors, unlike [⁸⁹Zr]Zr-Df-DINU, which displayed elevated tumor uptake, irrespective of hB7-H3 expression. Nontargeted [⁸⁹Zr]Zr-Df-bsAb CTRL isotype control showed markedly lower uptake in all tested tumor models. Overall, bispecific antibodies binding GD2 and B7-H3 showed improved selectivity for targeting tumor cells expressing both antigens. This approach may enhance antitumor efficacy while addressing the toxicity limitations of current GD2-targeting therapies by reducing off-tumor GD2 binding in nerves.

2025-06-20·Theranostics

GD2-mediated impairment of macrophage phagocytosis drives pulmonary metastasis in osteosarcoma

Article

作者: Ge, Jun ; Song, Zhuorun ; Zhou, Quan ; He, Yunfei ; Wang, Chunjie ; Yang, Huilin ; Ding, Peng ; Zhang, Zeng ; Liu, Tao ; Yang, Peng ; Hou, Guanghui ; Lu, Shunyi ; Wu, Jichuan

Rationale: The lung is the most common site of metastasis in osteosarcoma, with pulmonary dissemination accounting for most of the disease-related mortality. Despite its clinical significance, the underlying mechanisms is poorly defined. Methods: To investigate the clinical relevance of GD2, we performed GD2 immunofluorescence staining on a cohort of human tumor samples. To explore the functional role of GD2 in lung metastasis, we employed an intravenous injection model and an intratibial injection model using U2OS and 143B cells respectively. To elucidate how GD2 regulates osteosarcoma lung metastasis, we carried out an in vitro flow-based phagocytosis assay. Results: We identify the disialoganglioside GD2 as a key mediator of osteosarcoma lung metastasis through impairing macrophage phagocytic function. Mechanistically, GD2 interacts with SIGLECE in mice (or SIGLEC7 in humans) on the cell surface of macrophages, leading to the activation of SH2-containing protein tyrosine phosphatase 2 (SHP2), which in turn suppresses macrophage phagocytic function. Notably, co-treatment with an anti-GD2 antibody and the SHP2 inhibitor SHP099 resulted in a synergistic reduction of lung metastasis. Conclusion: Our findings uncover a mechanism of osteosarcoma lung metastasis and highlight the GD2-SIGLEC-SHP2 axis as a promising therapeutic target.

项与 Daretabart 相关的新闻（医药）

2026-04-24

·国际干细胞与免疫细胞研究

生存率77%+癌标降96%+十线耐药仍CR！国研NK弯道超车，横扫肺癌/乳腺癌/肠癌/淋巴瘤等

点击蓝字关注我们 NK细胞被誉为人体抗肿瘤、抗感染的免疫第一道防线，1975年被科学家正式发现鉴定，是先天免疫里不可或缺的抗癌主力军。2026年2月，ASCO重磅指南更新，正式将NK细胞疗法纳入晚期肺癌二线及以上标准治疗方案，再度引爆行业关注。不止国际认可，我国NK细胞临床研究早已硕果累累：暨南大学和广州复大肿瘤医院团队针对复发乳腺癌、晚期非小细胞肺癌等癌种均斩获亮眼疗效，为万千肿瘤患者开辟全新康复出路，点亮生命曙光！人体自带的抗癌精锐NK细胞，全方位围剿癌细胞何谓NK细胞疗法？ PART 01 自然杀伤细胞（简称NK细胞）是一类独特的淋巴细胞亚群，体积大于T淋巴细胞和B淋巴细胞，且含有独特的细胞质颗粒。作为先天免疫的核心力量，NK细胞具备直接杀灭癌细胞的能力，其优势在于无需依赖MHC-I分子和抗体，就能精准识别并清除肿瘤细胞。除直接杀伤外，NK细胞还能通过独特的免疫调节功能间接助力抗癌。它可调控树突状细胞、巨噬细胞、T细胞、B细胞等多种免疫细胞的功能，促使这些细胞相互作用，产生多种细胞因子、生长因子和趋化因子；同时，NK细胞分泌的细胞因子还能调节B细胞产生抗肿瘤抗体的过程。更值得一提的是，NK细胞杀死癌细胞后，癌细胞会将癌抗原递呈给树突状细胞，促进其成熟并启动抗原呈递；而活化的NK细胞还能裂解正在吞噬加工外源抗原的外周树突状细胞，释放更多抗原细胞碎片，进一步强化机体抗肿瘤免疫反应，全方位围剿癌细胞。 ▼NK细胞正在绞杀癌细胞 ▲图源“Isaac Chan, M.D,Ph.D”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除注：蓝色肿瘤类器官，在被红色NK细胞包围。 NK细胞在血液肿瘤及实体瘤领域“大展拳脚” PART 02 近二十年来，NK细胞疗法在肿瘤治疗领域逐渐崭露头角，尤其在血液肿瘤治疗中展现出巨大潜力。相较于传统治疗手段，NK细胞疗法不仅安全性更高、适用范围更广，这一优势在实体瘤治疗领域同样得到充分体现。目前，全球范围内正紧锣密鼓开展超过100项NK细胞疗法相关临床研究，聚焦不同来源的NK细胞，全力挖掘其治疗潜能。其中，在乳腺癌、肝癌、消化道肿瘤等实体瘤治疗中，NK细胞疗法已取得振奋人心的临床成果，让他们在抗癌路上拥有了更多可能。 · 泛癌症范畴内，NK细胞治疗的癌症类型 · ▲图源“cell”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除我国两款NK细胞研究双双出圈，解锁肺癌/乳腺癌治疗新方案复大研究登国际顶刊！NK联合疗法治肺癌，全方位碾压单一治疗，一例肿瘤直接“腰斩”，从3.5cm缩小至1.3cm PART 01 广州复大肿瘤医院一项研究（NCT02845856）显示，NK细胞联合西妥昔单抗可作为晚期非小细胞肺癌（NSCLC）患者的放化疗替代方案，能显著延长患者生存期，相关成果发表于《美国癌症研究杂志》。该研究纳入54例晚期EGFR过表达NSCLC患者，分为两组（各27例），即A组（采用NK细胞联合西妥昔单抗治疗）、B组（单独使用西妥昔单抗治疗）。结果显示：A组临床疗效及患者生活质量、免疫功能均显著优于B组（P< 0.05）： 1、临床有效率方面：A组4例达部分缓解（PR）、17例达病情稳定（SD）。 2、生活质量上：治疗后A组KPS评分提高≥10分者占74.7%，远高于B组的51.9%，治疗前两组KPS评分分别为73.7±6.4（A组）、72.8±7.5（B组），3个月后分别提升至82.96±13.03、75.78±14.83。 3、生存期方面：A组中位总生存时间（OS）为9.5个月（详见下图B）、中位无进展生存时间（PFS）6个月，均优于B组的7.5个月（OS）、4.5个月（PFS）（详见下图A）。 ▲图源“Am J Cancer Res”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除值得一提的是，一位53岁IVA期NSCLC男性患者，经该联合方案治疗后肿瘤显著缩小，CT扫描显示其右肺肿瘤从治疗前的3.5×3.5 cm，缩小至1.7×1.3 cm（详见下图）。 ▲图源“Am J Cancer Res”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除暨南大学重磅研究！NK细胞强势狙击复发性乳腺癌，治疗2个月病灶大幅消退 PART 02 暨南大学研究团队开展的一项“NK细胞治疗复发性乳腺癌临床研究（NCT02853903）”中，共纳入36例病理确诊的复发性乳腺癌患者，其中一位46岁患者的显著疗效引发关注。该患者治疗前后的影像学变化尤为典型：治疗前CT扫描显示，其右乳存在8.0×3.8×5.7cm的软组织肿块，边界模糊，增强CT呈中度不均匀强化；腋窝可见多处肿大淋巴结，最大者约2.9×1.7×3.8cm（详见下图A）。经NK细胞治疗2个月后，影像学复查显示肿块缩小至6.8×3.5×5.8cm，强化程度减弱为轻度不均匀；腋窝肿大淋巴结亦显著缩小（详见下图B），展现出NK细胞疗法在复发性乳腺癌中的潜在抗肿瘤活性。 ▲图源“Dovepress”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 NK细胞还可用于治疗这些癌种，逐一攻破淋巴瘤、肠癌、神经母细胞瘤等 NK细胞打破难治白血病30年治疗僵局！58.3%患者起效，移植后1年OS高达60% PART 01 复发/难治性急性髓系白血病（R/RAML）患者预后较差，中位生存期仅3-8个月，30余年来预后无显著改善。对于这类患者，挽救治疗的根本目的是最大限度地控制病情，以便进行异基因造血干细胞移植（AHSCT）的巩固治疗，后者仍有可能让部分患者达到临床治愈。本文报告《美国血液学杂志》上一项I期临床试验结果，旨在评估单倍体FC21扩增NK细胞治疗R/RAML的安全性与可行性。该研究共纳入12例难治性AML患者（6例原发性难治、6例复发，含5例移植后复发），中位年龄60岁，多为高疾病风险，既往中位治疗5次，入组时中位骨髓原始细胞47%；采用氟达拉滨/阿糖胞苷方案治疗后，输注6次NK细胞。结果显示：58.3%患者（7例）对治疗有反应（4例CR、3例CRi，1例CR伴MRD阴性），中位最佳疗效时间48天（范围：16-83天）。 ▲图源“Am J Hematol”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除中位随访52个月（范围49–55个月），全队列1年总生存率(OS)为41.7%（95%CI：15.25–66.53），无事件生存率(EFS)为25%（95%CI：6.01–50.48）。CR/CRi患者及接受AHSCT患者1年OS分别达57.14%和60%，显著高于无反应及未移植患者（p值均<0.01，详见下图C）。 ▲图源“Am J Hematol”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 AACR重磅案例：AFM13联合NK细胞，拯救十线耐药淋巴瘤，从全身转移到完全缓解！ PART 02 2022年美国癌症研究学会（AACR）年会上，一例经AFM13NK细胞治疗后达到完全缓解的高度难治性霍奇金淋巴瘤病例引发广泛关注。该患者为37岁男性，既往接受十线治疗（包括派姆单抗、高剂量化疗/自体干细胞移植、ABVD、GDP方案等），疾病仍持续进展，影像学显示全身弥漫性淋巴结受累，并伴肺及骨骼转移。患者以最后希望入组接受异体NK细胞+AFM13联合治疗。 AFM13是全球首创四价双特异性先天免疫细胞衔接器，可特异性结合CD30阳性肿瘤细胞，桥接并激活NK细胞与巨噬细胞，通过先天免疫系统精准杀伤肿瘤幸运的是，该患者在治疗后，竟奇迹般地获得了完全缓解（CR），全身病灶显著消退（详见下图）！ ▲图源“AFFIMED”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除高危神经母细胞瘤迎来NK联合突围方案，61.5%有效率+1年生存率77%！ PART 03 高危神经母细胞瘤是一种极具侵袭性的儿童肿瘤，恶性程度高、预后凶险。抗GD2单克隆抗体可靶向结合肿瘤表面GD2抗原，与GM-CSF、IL-2、异维A酸联用已纳入该病标准治疗。临床常规多在肿瘤负荷较低时使用抗GD2单抗，规避化疗免疫抑制削弱抗体杀伤作用；但已有研究证实，肿瘤体积偏大时，单抗与化疗联用仍有显著协同抗癌效果。《临床癌症研究》发布一项临床试验（NCT01576692），首次探索人源化抗GD2单克隆抗体（hu14.18K322A）+细胞毒性化疗+NK细胞，联合治疗复发/难治性神经母细胞瘤的效果。该研究共入组13例既往多线治疗失败的神经母细胞瘤患儿，多数曾接受抗GD2单抗、清髓化疗及自体干细胞移植，最终11例完成异基因NK细胞输注。临床结果亮眼：总有效率（ORR）达61.5%（4例完全缓解，1例非常好的部分缓解，3例部分缓解，5例病情稳定），CR/VGPR率（完全缓解/非常好的部分缓解率）达38.5%；治疗期间无患者病情进展，有症状患儿均得到明显改善。中位疾病进展时间（TTP）为274天（范围：239-568天），1年生存率（OS）高达77%（95%CI，48-93%），且体内呈现明显免疫激活状态。 ▲截图源自“AACR” 综上，相较于既往单纯化疗15%–50%的缓解率、极少完全缓解的现状，本联合方案在多线耐药患儿中仍能实现更高缓解率与长期生存获益。十线耐药也能CR！NK+αβT细胞助高龄肠癌患者逆袭，肿瘤标志物断崖式暴跌96%，生存逼近2.6年 PART 04 《转化肿瘤学研究》刊发了一个“应用NK+αβT细胞联合免疫治疗，助晚期结直肠癌患者实现术后完全缓解”的典型临床案例。该患者是一位81岁女性，因不明原因暗红色便血就医，最终确诊为结直肠癌；合并20年高血压、10年骨质疏松。肠镜见不规则肿块占据肠腔2/3，无法穿刺活检；肿瘤标志物显著升高，癌胚抗原（CEA）48.13ng/mL、CA199达75.86U/mL、CA125达64.13IU/mL，影像学确诊直肠乙状结肠占位伴肝脏多发转移（详见下图A）。患者行腹腔镜肠道肿瘤+左肝转移灶切除术，术中清除浅表肝转移灶，但部分深部低密度病灶无法完整切除。术后病理提示分化型腺癌侵及浆膜、伴淋巴结转移，肝内病灶为肿瘤转移，手术切缘未见癌细胞残留。术后予卡培他滨辅助化疗，CEA一度降至19.52ng/mL，短期内却快速反弹。后续入组接受6疗程NK+αβT细胞静脉输注免疫治疗。疗效数据十分亮眼：首次细胞输注后CEA即明显回落，由14.7ng/mL降至6.1ng/mL；4个疗程后更是降至1.9ng/mL，恢复至正常参考水平。影像复查显示肝转移灶大幅缩小、密度趋近正常肝组织（详见下图B、C），原最大13.44mm×10.81mm病灶已不可测量，临床评估达到。 ▼该患者肝转移灶过继免疫治疗前（图A）、治疗后（图B）CT扫描及增强CT扫描（图C） ▲图源“TCR”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除更为惊喜的是，经19个月长期随访，患者无复发、无明显并发症；该疗法总有效率（ORR）达83.3%，中位无进展生存期（PFS）达567天，总生存期（OS）长达966天（≈2.6年）。综上，该案例充分印证：过继性细胞免疫联合辅助化疗，可为晚期结直肠癌患者提供安全、有效的全新治疗路径。小编寄语 NK细胞可在第一时间发现并启动机体的免疫防御机制，及时发现并将癌细胞扼杀在“摇篮”，是公认的人体抗癌第一道防线，可达到长期抗肿瘤免疫。小编也希望这篇文章能让更多癌友，了解NK细胞的前沿进展，并期待NK细胞在临床应用中能获得更多的突破，为预防肿瘤复发及转移助上一臂之力！如果您对目前的治疗方案不满意，或想寻求NK细胞、CAR-NK细胞等国内外其他抗癌新技术的帮助，可扫文末二维码，将住院经历、治疗经历、近期病理检查结果等资料，提交至国际干细胞与免疫细胞研究医学部，进行初步评估或申请国内外专家会诊。参考资料 [1]Liang S,et al.Cetuximab combined with natural killer cells therapy: an alternative to chemoradiotherapy for patients with advanced non-small cell lung cancer (NSCLC). Am J Cancer Res. 2018 May 1;8(5):879-891. https://pmc.ncbi.nlm.nih.gov/articles/PMC5992505/ [2]Ciurea SO,et al.Results of a phase I trial with Haploidentical mbIL-21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML. Am J Hematol. 2024 May;99(5):890-899. https://pmc.ncbi.nlm.nih.gov/articles/PMC12577216/ [3]Federico SM,et al.A Pilot Trial of Humanized Anti-GD2 Monoclonal Antibody (hu14.18K322A) with Chemotherapy and Natural Killer Cells in Children with Recurrent/Refractory Neuroblastoma. Clin Cancer Res. 2017 Nov 1;23(21):6441-6449. https://pmc.ncbi.nlm.nih.gov/articles/PMC8725652/#T5 [4]Li S,et al. Significant clinical response of advanced colorectal cancer to combination therapy involving capecitabine and adoptive cell transfer therapy: a case report[J]. Translational Cancer Research, 2019, 8(2): 693. https://tcr.amegroups.org/article/view/27354/html [5]https://www.affimed.com/affimed-announces-oral-presentation-of-phase-1-2-data-from-afm13-in-combination-with-allogeneic-nk-cells-at-the-2023-ash-annual-meeting/ 本文为“国际干细胞与免疫细胞研究”原创，转载需授权干细胞与免疫细胞研究入群免费领取抗癌细胞资讯｜新技术｜新药研发｜权威专家资料求分享求收藏求点击求在看

2026-04-14

·BioSpace

Renaissance Pharma Limited, an Essential Pharma company, secures FDA Fast Track Designation and IND clearance for Daretabart (hu1418K322A) in high-risk neuroblastoma

FDA grants Fast Track Designation for Daretabart (hu1418K322A), recognising the significant unmet medical need in high-risk neuroblastoma and enabling access to accelerated and rolling review FDA clearance of IND application enables initiation of the SHINE Phase II/III clinical trial in relapse and refractory patients with high-risk neuroblastoma First commercial-scale GMP batch of Daretabart (hu1418K322A) successfully manufactured Programme builds on positive Phase II data which demonstrated overall survival rate of 86.0% UK – 14 April 2026 – Renaissance Pharma Limited, an Essential Pharma company focused on development stage assets, today announces that the US Food and Drug Administration (FDA) has granted Fast Track Designation for Daretabart (hu1418K322A), a novel anti-GD2 monoclonal antibody in development for the treatment of high-risk neuroblastoma (HRNB), a rare paediatric cancer. The designation recognises the significant unmet medical need in HRNB and will support more frequent interactions with the FDA throughout development, as well as eligibility for accelerated and rolling review. The company also confirms it has received IND clearance from the FDA, enabling initiation of the SHINE Phase II/III clinical trial in relapse or refractory children with HRNB in the United States. The first commercial-scale Good Manufacturing Practice (GMP) batch of Daretabart (hu1418K322A) has also been successfully manufactured for use in the SHINE trial. Daretabart (hu1418K322A) is being developed by Renaissance Pharma under an exclusive license agreement with St. Jude Children's Research Hospital, a global leader in pediatric cancer research and treatment. The antibody targets GD2, a cell surface antigen highly expressed on neuroblastoma cells. By binding to GD2, Daretabart (hu1418K322A) is designed to enhance immune-mediated tumour cell killing, while incorporating novel structural modifications intended to improve tolerability profile. The programme builds on encouraging Phase II data evaluating Daretabart (hu1418K322A) as part of first-line therapy and in the post-consolidation setting for patients with HRNB. The study demonstrated a three-year event-free survival (EFS) rate of 73.7% and an overall survival (OS) rate of 86.0%. These results were published in the Journal of Clinical Oncology in December 2021. The successful manufacture of the first commercial-scale GMP batch marks a key operational milestone and underscores Renaissance Pharma’s commitment to ensuring reliable, high-quality supply as the programme advances. This achievement supports ongoing clinical development and represents an important step towards future commercial readiness. Simon Ball, Interim CEO of Essential Pharma and Director of Renaissance Pharma Limited said : “ Daretabart has the potential to make a real difference for children with high-risk neuroblastoma, a disease where outcomes remain deeply inadequate despite intensive treatment. FDA Fast Track Designation is an important external validation of that potential, and together with IND clearance and our ability to manufacture at commercial scale, reflects the strength and maturity of this programme. Having worked exceptionally hard behind the scenes for a number of months, it is with great excitement that we announce this update today. We are executing at pace, and look forward to sharing data from the SHINE trial as it progresses. Today’s news brings us another step closer to delivering Daretabart as a meaningful new treatment option for children facing this aggressive cancer.” References 1 Furman WL, McCarville B, Shulkin BL, Davidoff A, Krasin M, Hsu CW, et al. Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. Journal of Clinical Oncology [Internet]. 2022 Feb 1;40(4):335–44. Available from: 2 News Medical Life Sciences. European scientists target high-risk childhood cancer with liquid biopsy. Available from: St. Jude Children’s Hospital. - About Renaissance Pharma Renaissance Pharma Limited, an Essential Pharma company, focused on development stage assets, is currently focused on improving treatment options within rare paediatric diseases. Lead candidate – Daretabart (hu1418K322A) is targeting the treatment of neuroblastoma. About Essential Pharma Essential Pharma is a global pharmaceutical company developing and delivering medicines for patients in niche populations. Our growing product portfolio reaches patients in approximately 70 countries and covers multiple therapy areas with a particular focus on speciality medicines used to treat rare diseases and cardiorespiratory disease. Our first development-stage asset, managed through our wholly owned subsidiary, Renaissance Pharma Limited, is an anti-GD2 antibody for the treatment of high-risk neuroblastoma – Daretabart (hu1418K322A). We challenge convention and work smarter to help ensure patients in small, underserved or rare disease populations have access to the medicines they need. For more information, visit About Neuroblastoma Neuroblastoma represents 7-10% of all childhood cancers and is the most common extracranial cancer in children and the most common cancer in children under one year of age. Each year, more than 1,500 people are diagnosed in Europe and 800 in the United States. Approximately half of all neuroblastoma patients have high risk (HRNB) disease which has an overall five-year survival of ~50%. The current standard of care is intensive and multimodal, including chemotherapy, surgery, radiotherapy, stem cell transplantation and anti-GD2 monoclonal antibody (mAb) treatment. Despite these interventions, a significant unmet medical need remains for more effective and better-tolerated treatments for HRNB 1,2 CONTACTS Essential Pharma Simon Ball Interim Chief Executive Officer Tel: +44 (0)1784 477 167 Email: info@essentialpharmagroup.com ICR Healthcare Tracy Cheung/Chris Welsh Email: Essentialpharma@icrhealthcare.com

2026-04-14

·allsci.com

Renaissance Pharma’s daretabart GD2-targeted mAb gains FDA Fast Track for high-risk neuroblastoma

Renaissance Pharma Ltd, a wholly owned subsidiary of Essential Pharma and headquartered in the UK, announced that the US FDA has granted Fast Track Designation for Daretabart (hu1418K322A), a GD2-targeted monoclonal antibody, for the treatment of high-risk neuroblastoma (HRNB). The company simultaneously confirmed Investigational New Drug (IND) clearance, enabling US initiation of the SHINE Phase II/III trial in relapsed or refractory paediatric HRNB patients. Daretabart is developed under an exclusive licence from St. Jude Children’s Research Hospital. Fast Track Designation gives Renaissance Pharma more frequent interactions with the FDA throughout development and eligibility for rolling and accelerated review of any future marketing application. The designation does not itself confer approval or alter the evidentiary standard required. The clinical rationale for the designation draws on a Phase II study of the antibody — then designated hu14.18K322A — evaluating it as first-line and post-consolidation therapy in HRNB patients. Updated results, published in the Journal of Clinical Oncology in February 2022, reported a three-year event-free survival (EFS) rate of 73.7% and an overall survival (OS) rate of 86.0%. No data cutoff date or patient number was disclosed in the press release for this study. The SHINE trial, now cleared to enrol in the United States, targets a narrower population: children with relapsed or refractory HRNB. Daretabart binds GD2, a disialoganglioside cell-surface antigen expressed at high density on neuroblastoma cells. The antibody is designed to enhance immune-mediated tumour cell killing. Renaissance Pharma states that the molecule incorporates structural modifications intended to improve its tolerability profile relative to earlier-generation anti-GD2 antibodies, though no technical characterisation of those modifications — such as Fc engineering specifics or comparative binding data — was disclosed in the announcement. The company also confirmed that the first commercial-scale Good Manufacturing Practice (GMP) batch of Daretabart has been produced for use in the SHINE trial. Research context Neuroblastoma accounts for 7%-10% of all childhood cancers and is the most common extracranial solid tumour in children under one year of age. Approximately 800 new cases are diagnosed annually in the United States and more than 1,500 in Europe. Roughly 50% of all neuroblastoma patients present with high-risk disease, which carries a five-year overall survival rate of approximately 50% despite multimodal treatment — comprising induction chemotherapy, surgery, high-dose consolidation with autologous stem cell rescue, radiotherapy, and maintenance immunotherapy. The current standard of care in HRNB already includes anti-GD2 monoclonal antibody therapy. Dinutuximab (Unituxin, United Therapeutics) received FDA approval in 2015 for pediatric patients with HRNB who had achieved at least a partial response to prior first-line multiagent, multimodal therapy. Dinutuximab beta (Qarziba, EUSA Pharma) holds European approval. Both agents target GD2 and are associated with infusion-related pain, a consequence of GD2 expression on peripheral nerve fibres. Renaissance Pharma’s claim that Daretabart incorporates modifications to improve tolerability positions the antibody as a potential successor in the same mechanistic class, though head-to-head comparative data are not yet available. The relapsed or refractory HRNB setting targeted by the SHINE trial remains without a dedicated approved therapy, and response rates to salvage regimens in this population are low. The five-year survival for patients who relapse after standard therapy is estimated at below 10% in published literature, establishing the basis for the FDA’s recognition of unmet medical need in granting Fast Track status. Leave a Reply Cancel reply Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

100 项与 Daretabart 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
高风险神经母细胞瘤	临床2期	美国	St. Jude Children's Research Hospital, Inc.	2013-07-05
淋巴瘤	临床1期	美国	St. Jude Children's Research Hospital, Inc.	2014-10-10
尤文肉瘤	临床1期	美国	St. Jude Children's Research Hospital, Inc.	2008-10-08
黑色素瘤	临床1期	美国	St. Jude Children's Research Hospital, Inc.	2008-10-08
难治性神经母细胞瘤	临床1期	美国	St. Jude Children's Research Hospital, Inc.	2008-10-08
难治性骨肉瘤	临床1期	美国	St. Jude Children's Research Hospital, Inc.	2008-10-08

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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


NCT01857934 (CTgov)	临床2期	神经母细胞瘤 \| 高风险神经母细胞瘤	153	hu14.18K322A (NB2012 Therapy (Including Induction, Consolidation, and MRD) Antibody (hu14.18K322A))	獵鏇遞網廠齋獵鏇範構 = 蓋簾蓋膚襯築蓋範鑰鏇鏇積糧餘蓋鹽觸艱齋遞 (鹽憲壓獵餘鑰製窪鏇簾, 艱鏇衊齋醖鬱製築網淵 ~ 壓醖構鏇夢簾夢齋構廠)	-	2023-02-24
NCT01857934 (CTgov)	临床2期	神经母细胞瘤 \| 高风险神经母细胞瘤	153	NB2012+hu14.18K322A (NB2012 Therapy (Including Induction, Consolidation, and MRD) Plus Antibody (hu14.18K322A))	積觸鏇餘願鑰鹹窪遞積 = 齋鹽鑰蓋範顧艱襯鹹窪鑰艱醖窪醖網鑰繭遞範 (醖窪餘淵獵齋廠繭鬱遞, 淵齋夢遞顧顧積鏇鹹顧 ~ 壓鬱衊製築網夢齋蓋糧) 更多	-	2023-02-24
NCT01857934 (Pubmed \| J Clin Oncol)	临床2期	高风险神经母细胞瘤	-	hu14.18K322A	壓憲鬱築艱鹹構衊淵選(窪餘遞鹽構夢壓艱網廠) = 觸鹹衊鑰膚壓繭蓋獵選積鑰艱糧鑰繭選鹹簾積 (鏇淵願獵襯選齋簾製鬱, 60.0 ~ 83.4) 更多	积极	2022-02-01
NCT01857934 (Pubmed \| Clin Cancer Res) 人工标引	临床2期	神经母细胞瘤一线	42	Chemotherapy+hu14.18K322A	鑰蓋襯齋襯鑰簾襯顧觸(廠齋衊鹹選積廠積鹽糧) = 選壓築廠餘艱襯壓鏇窪壓積餘鑰繭築窪鹽蓋壓 (襯網餘選遞觸網積鬱壓, 70.9 ~ 93.3) 更多	积极	2019-11-01
NCT01576692 (Pubmed \| Clin Cancer Res) 人工标引	临床1期	复发性神经母细胞瘤 \| 难治性神经母细胞瘤	13	Chemotherapy+hu14.18K322A+NK cells	鬱鑰簾積糧積觸鬱膚積(夢獵觸鑰壓衊繭壓廠鏇) = One patient developed an unacceptable toxicity (grade 4 thrombocytopenia >35 days). Four patients discontinued treatment for adverse events (hu14.18K322A allergic reaction, viral infection, surgical death, second malignancy). Common toxicities included grade 3/4 myelosuppression (13/13 patients) and grade 1/2 pain (13/13 patients). 襯築膚衊顧構積獵築獵 (鏇醖艱顧醖構遞觸鹹願 )	积极	2017-11-01
NCT00743496 (Pubmed \| J Clin Oncol)	临床1期	神经母细胞瘤 GD2	-	Hu14.18K322A	廠鏇夢齋廠選遞獵簾遞(艱願製製淵壓壓選顧築) = 夢廠窪選糧簾選糧鹹網鑰遞齋壓築簾選醖蓋蓋 (網餘膚膚壓壓鹹鹹範鏇 )	-	2014-05-10