In this phase I clinical trial cancer patients suffering from solid tumors or lymphomas, recurring after and/or refractory against standard treatment are treated intravenously (iv) with increasing doses of tTF-NGR(tTF= truncated tissue factor; NGR=Asn-Gly-Arg). The objectives of this trial are to evaluate the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT) of intravenously (iv) infused daily applications of tTF-NGR for 5 days every 3 weeks in patients with cancer, who had obtained all standard treatment known for their disease entity prior to entry on study. Further objectives are to determine the perfusion and vascular volume fraction of measurable tumor lesions versus normal reference tissue before and after tTF-NGR application by MRI as a biological surrogate parameter for biological activity of the investigational medicinal product (IMP), tTF-NGR, and to obtain pharmacokinetic data.

开始日期2017-03-01

申办/合作机构

Universitätsklinikum Münster

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100 项与 tTF-NGR(University of Münster) 相关的临床结果

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100 项与 tTF-NGR(University of Münster) 相关的转化医学

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100 项与 tTF-NGR(University of Münster) 相关的专利（医药）

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项与 tTF-NGR(University of Münster) 相关的文献（医药）

2023-11-02·Human reproduction (Oxford, England)

Impact of low- or moderate-risk gonadotoxic chemotherapy prior to testicular tissue freezing on spermatogonia quantity in human (pre)pubertal testicular tissue

Article

作者: Liard, Agnès ; Rives, Nathalie ; Rondanino, Christine ; Barbotin, Anne-Laure ; Bubenheim, Michael ; Ancelle, Amélie ; Daudin, Myriam ; Mirallié, Sophie ; Giscard d'Estaing, Sandrine ; Brugnon, Florence ; Dumont, Ludovic ; Feraille, Aurélie ; Roux, Christophe ; Schneider, Pascale

Abstract:

STUDY QUESTION:

What is the impact of low- or moderate-risk gonadotoxic chemotherapy received prior to testicular tissue freezing (TTF), and of the cancer itself, on spermatogonia quantity in testicular tissue from (pre)pubertal boys?

SUMMARY ANSWER:

Vincristine, when associated with alkylating agents, has an additional adverse effect on spermatogonia quantity, while carboplatin has no individual contribution to spermatogonia quantity, in testicular tissue of (pre)pubertal boys, when compared to patients who have received non-alkylating chemotherapy.

WHAT IS KNOWN ALREADY:

The improved survival rates after cancer treatment necessitate the inclusion of fertility preservation procedures as part of the comprehensive care for patients, taking into consideration their age. Sperm cryopreservation is an established procedure in post-pubertal males while the TTF proposed for (pre)pubertal boys remains experimental. Several studies exploring testicular tissue of (pre)pubertal boys after TTF have examined the tubular fertility index (TFI, percentage of seminiferous tubule cross-sections containing spermatogonia) and the number of spermatogonia per seminiferous tubule cross-section (S/T). All studies have demonstrated that TFI and S/T always decrease after the introduction of chemotherapeutic agents, especially those which carry high gonadotoxic risks such as alkylating agents.

STUDY DESIGN, SIZE, DURATION:

Testicular tissue samples from 79 (pre)pubertal boys diagnosed with cancer (from 6 months to 16 years of age) were cryopreserved between May 2009 and June 2014. Their medical diagnoses and previous chemotherapy exposures were recorded. We examined histological sections of (pre)pubertal testicular tissue to elucidate whether the chemotherapy or the primary diagnosis affects mainly TFI and S/T.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

(Pre)pubertal boys with cancer diagnosis who had been offered TTF prior to conditioning treatment for hematopoietic stem cell transplantation were included in the study. All the patients had previously received chemotherapy with low- or moderate-risk for future fertility. We have selected patients for whom the information on the chemotherapy received was complete. The quantity of spermatogonia and quality of testicular tissue were assessed by both morphological and immunohistochemical analyses.

MAIN RESULTS AND THE ROLE OF CHANCE:

A significant reduction in the number of spermatogonia was observed in boys treated with alkylating agents. The mean S/T values in boys exposed to alkylating agents were significantly lower compared to boys exposed to non-alkylating agents (P = 0.018). In contrast, no difference was observed for patients treated with carboplatin as the sole administered alkylating agent compared to the group of patients exposed to non-alkylating agents. We observed an increase of S/T with age in the group of patients who did not receive any alkylating agent and a decrease of S/T with age when patients received alkylating agents included in the cyclophosphamide equivalent dose (CED) formula (r = 0.6166, P = 0.0434; r = −0.3759, P = 0.0036, respectively). The TFI and S/T decreased further in the group of patients who received vincristine in combination with alkylating agents (decrease of 22.4%, P = 0.0049 and P < 0.0001, respectively), but in this group the CED was also increased significantly (P < 0.0001). Multivariate analysis, after CED adjustment, showed the persistence of a decrease in TFI correlated with vincristine administration (P = 0.02).

LIMITATIONS, REASONS FOR CAUTION:

This is a descriptive study of testicular tissues obtained from (pre)pubertal boys who were at risk of infertility. The study population is quite heterogeneous, with a small number of patients in each sub-group. Our results are based on comparisons between patients receiving alkylating agents compared to patients receiving non-alkylating agents rather than chemotherapy-naive patients. The French national guidelines for fertility preservation in cancer patients recommend TTF before highly gonadotoxic treatment. Therefore, all the patients had received low- or moderate-risk gonadotoxic chemotherapy before TTF. Access to testicular tissue samples from chemotherapy-naive patients with comparable histological types of cancer was not possible. The functionality of spermatogonia and somatic cells could not be tested by transplantation or in vitro maturation due to limited sample sizes.

WIDER IMPLICATIONS OF THE FINDINGS:

This study summarizes the spermatogonial quantity of (pre)pubertal boys prior to TTF. We confirmed a negative correlation between the cumulative exposure to alkylating agents and spermatogonial quantity. In addition, the synergistic use of vincristine in combination with alkylating agents showed a cumulative deleterious effect on the TFI. For patients for whom fertility preservation is indicated, TTF should be proposed for chemotherapy with a predicted CED above 4000 mg/m2. However, the data obtained from vincristine and carboplatin use should be confirmed in a subsequent study including more patients.

STUDY FUNDING/COMPETING INTEREST(S):

This study had financial support from a French national research grant PHRC No. 2008/071/HP obtained by the French Institute of Cancer and the French Healthcare Organization. The sponsors played no role in the study. The authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER:

N/A.

2023-11-01·The Journal of hospital infection

Bacterial contamination of water used as thermal transfer fluid in fluid-warming devices

Article

作者: Indra, A ; Kimberger, O ; Schnetzinger, M ; Heger, F

INTRODUCTION:

Recent reports implicated heater-cooler units (HCUs), which are used for warming infusions, blood or in extracorporeal membrane oxygenation devices, as a possible origin of healthcare-associated infections (HAIs) with potentially pathogenic bacteria, such as non-tuberculous mycobacteria [1]. This represents a source of contamination in a usually sterile setting.

AIM:

To analyse water from infusion heating devices (IHDs) for bacterial contamination, and to determine if IHDs are a potential source in the transmission of HAIs.

METHODS:

Thermal transfer fluid (TTF; 300-500 mL) was collected from the reservoirs of 22 independent IHDs and processed on different selective and non-selective media for colony count and identification of bacteria. Strains of Mycobacterium spp. were analysed by whole-genome sequencing.

RESULTS:

Bacterial growth was observed in all 22 TTF samples after cultivation at 22 °C and 36 °C. Pseudomonas aeruginosa was the most frequent pathogen identified, present in 13.64% (3/22) of samples at >100 colony-forming units/100 mL. Colonization with Mycobacterium chimaera, Ralstonia pickettii and Ralstonia mannitolilytica was detectable in 9.09% (2/22) of samples. Primary sequencing of the detected M. chimaera suggests a close relationship with a M. chimaera strain detected in an outbreak in Switzerland which led to the death of two patients.

DISCUSSION:

Contamination of TTF represents a germ reservoir in a sensitive setting. Handling errors of IHDs may lead to the distribution of opportunistic or facultative bacterial pathogens, increasing the risk of transmission of nosocomial infections.

2023-09-27·Molecules (Basel, Switzerland)

A Rapid and Quantitative Method for Determining Seed Viability Using 2,3,5-Triphenyl Tetrazolium Chloride (TTC): With the Example of Wheat Seed.

Article

作者: Zhong, Sunyaxin ; Sun, Jing ; Mao, Xinyue ; Wang, Shuonan ; Wu, Mengmeng ; Qiu, Nianwei ; Zhou, Feng

Current colorimetric methods for quantitative determination of seed viability (SV) with 2,3,5-triphenyl tetrazolium chloride (TTC) have been plagued by issues of being cumbersome and time-consuming during the experimental process, slow in extraction and staining, and exhibiting inconsistent results. In this work, we introduced a new approach that combines TTC-staining with high-temperature extraction using dimethyl sulfoxide (DMSO). The optimization of the germination stage, TTC-staining method, and 1,3,5-triphenylformazan (TTF) extraction method were meticulously carried out as follows: When the majority of wheat seeds had grown the radicle, and the length of radicles was approximately equal to the seed length (24 h-germination), 2 g germinating seeds were placed into a beaker (20 mL) containing 5 mL 10 g·L^-1 TTC solution. The seeds were stained with TTC in the dark at 25 °C for 1 h. Following the staining, 1 mL 1 mol·L^-1 H₂SO₄ was added to stop the reaction for 5 min. The H₂SO₄ solution was then removed, and the seeds were gently rinsed with deionized water. Subsequently, the TTF produced in the seeds was extracted directly with 5 mL DMSO solution at 55 °C for 1 h. The absorbance of the extract was measured at 483 nm, and the index of SV was calculated according to a predetermined TTC calibration curve and expressed by mg TTC·g^-1 (seed)·h^-1. The new method has been demonstrated to be rapid, stable, and highly sensitive, as evidenced by the accurate measurement of seed viability with different aging degrees.

项与 tTF-NGR(University of Münster) 相关的新闻（医药）

2024-01-23

·今日头条

全新抗癌“黑科技”！电场疗法显著延长肺癌生存期，2024上市在望

显著延长生存期，肺癌患者又将迎来一款全新的抗癌黑科技！放眼全球，肺癌仍是导致死亡排名第一的癌症，尽管靶向、免疫治疗已经取得了重大进展，但这些治疗方式存在一定的毒性，肺癌患者的耐受性和依从性都面临巨大挑战！研究人员一直在研发全新的治疗方式，让患者尽量避免药物的副作用，放疗的并发症，在达到更好治疗效果的同时保证高质量生活。 2023年美国临床肿瘤学会（ASCO）年会上，电场疗法代号为LUNAR的III期临床实验公布更新振奋人心的结果，显著延长了肺癌患者的生存期！更好的消息是，基于此积极数据，美国Novocure公司已在 2023年12月15日向FDA提交非小细胞肺癌适应症的上市申请，拟用于与标准全身治疗方案联合，治疗在含铂治疗期间或之后进展的非小细胞肺癌期望在2024年下半年收到FDA的监管决定。如果一切顺利，这将是电场疗法获批的暨胶质母细胞瘤和胸膜间皮瘤后的第三大适应症，将给全球死亡率排名第一的肺癌带来全新的治疗变革！肺癌患者迎来全新抗癌“黑科技”！电场疗法显著延长总生存期关键的全球随机 3 期代号为LUNAR的研究取得成功，达到了主要终点！截止 2022 年 11 月 26 日，276 名晚期化疗后进展的非小细胞肺癌患者以 1:1 的比例随机接受电场疗法（ TTFields ）加 SOC（免疫检查点抑制剂或多西紫杉醇）或单独接受 SOC。最终的研究结果显示：在进展后的转移性非小细胞肺癌 (NSCLC) 患者中，与单独使用化疗或者免疫治疗相比，电场疗法联合治疗组均显著改善了晚期非小细胞肺癌患者的总生存期，并且死亡风险降低了 26%！在意向治疗 (ITT) 人群中：电场疗法加 SOC 的中位总生存期（ OS）为 13.2 个月，而单独使用 SOC 时为 9.9 个月；电场疗法加 SOC 的1 年和 3 年总生存（ OS ）率分别为 53%和 18% ，而单独 SOC 组为 42%和 7% ，这意味着晚期肺癌的3年总生存率翻了2倍多！其中，在接受免疫检查点抑制剂治疗的患者中加入电场疗法，中位总生存期（ OS ）为 18.5 个月，而单独使用 SOC 时为 10.6 个月，将死亡率降低 37% 。在接受多西他赛治疗的患者中加入电场疗法，中位总生存期（ OS ）分别为 11.1 个月，单独使用 SOC 时为8.9 个月，将死亡风险降低 19%。值得一提的是，联合疗法的安全性较好。电场治疗组中最常见的任何级别 AE 是皮炎 (43%)、肌肉骨骼疼痛 (36%)、疲劳 (28%)、贫血 (23%)、呼吸困难 (20%)、腹泻 (19%)、恶心 ( 19%）、咳嗽（18%）、白细胞减少（17%）、肺炎（15%）、呼吸道感染（15%）、局部水肿（15%）和脱发（10%）。大多数与电场治疗相关的副作用是 1-2 级皮炎，87% 的病例在中位持续 3 周后得到解决。埃默里大学 Winship 癌症研究所的研究员和内科肿瘤学家Ticiana Leal博士说“LUNAR 试验是 7 年多来第一项显示转移性非小细胞肺癌铂类化疗后总生存期显着改善的研究。它可以帮助许多转移性肺癌患者在铂类疗法后获得新的治疗选择，而不会增加全身毒性！TTFields 疗法应被视为铂类化疗后进展的转移性非小细胞肺癌护理标准的一部分，TTFields 疗法是一种潜在的范式转变新治疗方式。” 电场疗法究竟是如何“电”死肿瘤的？通俗的说，电场疗法治疗肺癌的方式非常简单，接受电场治疗的肺癌患者只需要在胸部佩戴四个换能器阵列，这些换能器阵列可以非侵入性地向肿瘤病灶输送电场，甚至在患者晚上睡觉的时候，电场也会持续的杀灭肿瘤细胞，患者在治疗期间可以正常的生活，工作。那么电场真正的抗癌原理是什么？我们知道，癌细胞是一群快速有丝分裂，不受控制恶性增殖的细胞。我们在初中生物课上都学过,细胞分裂的时候是通过纺锤体把染色体拉到两端，形成两个新的细胞。而纺锤体，就像一条绳索，是依靠微管蛋白根据自身的极性规律聚集成簇形成的，帮助癌细胞完成快速的分裂. 那当我们把电场施加到癌细胞上的时候会发生什么呢？我们看到：在癌细胞分裂的中期，电场影响微管蛋白聚集成簇，阻止纺锤体形成，导致染色体无法正常分离；在癌细胞分裂的末期，电场将电荷推向分裂细胞的颈部，破坏癌细胞结构。这两种作用机制导致的最终结果都是抑制癌细胞正常分裂，最终出现表面膜起泡，癌细胞破裂，死亡。而更重要的是，这种治疗方式不是仅针对局部肿瘤病灶，而是全面扫荡体内存在的癌细胞，把敌人杀个片甲不留。 ▲分裂不能完成，癌细胞起泡、破裂，死~ 电场疗法已上市，国内患者如何申请？电场疗法自从问世以来就备受关注，这种针对快速有丝分裂的癌细胞的抗癌黑科技曾被国际著名癌症期刊Clinical Cancer Research发表的一篇文章誉为肿瘤治疗的第四种新方式。这也是有史以来最具科幻色彩的抗癌疗法，早在2011年起就已被FDA接连批准用于治疗复发性胶质母细胞瘤，新诊断的胶质母细胞瘤以及恶性胸膜间皮瘤。上市国家：美国，日本，中国（内地，香港）目前国内的患者可通过以下三种方式接受电场治疗：1.在医院接受正规治疗。电场疗法目前已经在美国，日本等多个国家获批上市，国内也已经获批上市，国内患者可前往指定医院进行正规治疗。（价格较高，可联系医学部咨询）美国1.2011年，FDA批准电场疗法用于复发的胶质母细胞瘤；2.2016年，FDA批准电场疗法用于新诊断的胶质母细胞瘤；3.2019年，FDA批准电场疗法用于间皮瘤。中国内地2020年5月，用于治疗组织学证实的复发性多形性胶质母细胞瘤（GBM）的成年患者（22岁或以上），以及与替莫唑胺联合治疗新诊断胶质母细胞瘤。中文大名--爱普盾。原文链接：十五年磨一剑！美国抗癌黑科技Optune终于在中国震撼上市！日本被诊断为恶性胶质瘤（GBM）的患者，在手术后完成放化疗治疗，之后联合化疗使用。2.参加临床试验。目前电场疗法在全球仍属于前瞻性研究，国内和国际都开展了大量的临床试验。3.日本ECCT疗法。日本作为医疗技术发达的国家之一，依据电场原理引进另一种设备，称为ECCT，经济条件有限的患者可以考虑。需要特别提醒大家的是，美国的电场疗法称为TTF，是被FDA批准的以及获得众多临床试验数据的权威肿瘤治疗方式。而日本的电场疗法称为ECCT依据电场的原理研发的，目前暂时没有大型的临床试验数据，在日本被再生医疗法批准，作为癌症的辅助治疗设备。此外TTF的费用相对较贵，日本的ECCT设备一套9万人民币左右，可购买回国内长期使用。患者可结合自身的经济条件等综合因素合理选择。这项疗法之所以非常值得期待，是因为电场独特的治疗原理赋予它可用于治疗多种实体瘤的特权，包括胃癌。而既往公布的电场治疗胰腺癌，卵巢癌，肝癌，肺癌的数据都非常令人振奋。我们也希望这电场疗法能尽快纳入医保，让更多的病友能接受这款有效的疗法，战胜癌症！本文为全球肿瘤医生网原创，未经授权严禁转载

ASCO会议临床3期临床结果免疫疗法

2023-09-04

·CPHI制药在线

临床 | 肿瘤电场疗法卵巢癌III期临床失败，前路漫漫亦灿灿

关注并星标CPHI制药在线 8月28日，Novocure宣布，肿瘤电场治疗（TTFields）与紫杉醇联合用于铂类耐药性卵巢癌患者的III期ENGOT-ov50/GOG-3029/INNOVATE-3临床试验在最终分析中没有达到总体生存期（OS）的主要终点。随机接受TTFields加紫杉醇治疗患者（n=280）的中位 OS 为12.2个月，单用紫杉醇治疗患者的中位生存期为11.9个月（n=278）（HR：1.008）。与先前报道的研究一致，TTFields治疗耐受性良好，未增加全身毒性。Novocure股价大跌37%。 ENGOT-ov50/GOG-3029/INNOVATE-3试验招募了最多有五种既往系统治疗线的患者。对探索性亚组的分析表明，以前只接受过一种治疗的患者有潜在的生存益处。鉴于约20%的卵巢癌症患者对一线铂治疗的反应有限，这一信号值得进一步探索。Novocure正在对ENGOT-ov50/GOG-3029/INNOVATE-3试验的数据进行全面评估，包括亚组分析。肿瘤治疗电场及其抗肿瘤机制肿瘤治疗电场（TTFields，Tumor Treating Fields）是一种利用特定电场频率干扰细胞分裂从而抑制肿瘤的疗法。这种由以色列公司Novocure开发的创新疗法，最初以对脑瘤患者治疗的突破性成就闻名，早在2011年时，Novocure的肿瘤电场疗法产品Optune就获得了FDA批准上市，用于治疗复发性胶质母细胞瘤（GBM）。另外，在临床试验中，Optune与化疗药物替莫唑胺TMZ联用表现出了比单药更好的疗效，显著地延长了GBM患者的生存期，这一联合疗法也在2015年获得了FDA批准。再鼎医药于2018年9月从Novocure公司获得了肿瘤电场治疗在大中华区的独家授权许可，并合作开发多个实体肿瘤适应症的临床研究。2020年6月，Optune（爱普盾®）在中国获批上市，再鼎医药的定价约为13万元/月，这个价格与Novocure公司在2015年招股书中披露的每月2.1万美金的Optune使用费用基本一致。根据再鼎医药公布2023年第二季度财报，爱普盾® Q2收入为1370万美元，同比增长18%。加上Q1收入的1330万美元，爱普盾2023H1收入约2700万美元。作为局部区域和非侵入性靶向治疗，TTFields 不像化疗等靶向全身的疗法那样，不会产生全身性的副作用，安全性高，报道的副作用主要为皮肤刺激。同时使用也较为方便，Novocure开发的家用Optune 设备，使GBM患者只用将仪器佩戴在头部就可接受治疗，甚至不影响日常生活活动。肿瘤电场治疗作为一种非侵入性的治疗方法，主要的治疗设备就是一件可以形成电场的可穿戴设备。它基于电生理的原理，通过低强度、中频（200kHz）的交变电场作用于癌细胞增殖所需的微管蛋白，阻碍微管（microtubule）的构建，从而干扰肿瘤细胞的有丝分裂，使受影响的肿瘤细胞凋亡。同时，它也通过电场力作用于癌细胞内各种物体及微小的带电的粒子（例如带极性的隔膜蛋白Septins），趁细胞分裂的时机破坏细胞。近年来，越来越多的证据支持肿瘤电场治疗与其他特定癌症疗法（包括放疗、某些化疗药物和某些免疫疗法）的广泛联用。随着科研人员和医学工作者对肿瘤电场治疗的研究更加深入，也总结出它的更多抗肿瘤机制，具体体现在如下四点：1. 干扰有丝分裂，协同化疗；2. 干扰肿瘤细胞迁移，协同抗血管治疗；3. 增强抗肿瘤免疫活性，协同免疫治疗4. 下调DNA损伤修复，协同放疗。 TTFields 抗肿瘤机制（图片出自：肿瘤资讯）目前电场疗法已被FDA批准用于治疗复发性胶质母细胞瘤、新诊断的胶质母细胞瘤以及恶性胸膜间皮瘤，并且在目前在六大实体肿瘤包括非小细胞肺癌、非小细胞肺癌脑转移、肝癌、胰腺癌、卵巢癌、乳腺癌的临床试验中都取得了惊人的数据，由于其原理是靶向杀灭所有快速有丝分裂的癌细胞，因此理论上适用于所有实体肿瘤。 NSCLCⅢ期临床达主要终点，股价却大跌今年6月，再鼎医药和Novocure在2023年美国临床肿瘤学会年会（ASCO 2023）上，公布了评估肿瘤电场治疗（TTFields）联合标准治疗用于非小细胞肺癌（NSCLC）的III期LUNAR研究阳性结果。数据显示，随机接受肿瘤电场治疗（TTFields）联合标准治疗的患者有137名，中位总生存时间为13.2个月，139名仅接受标准治疗的患者中位总生存时间为9.9个月，中位总生存时间具有显著统计学意义和临床意义的3个月改善，TTFields达到了OS（总生存期）的临床终点。且在免疫疗法的联合治疗中效果更佳，66名患者接受肿瘤电场治疗（TTFields）联合免疫治疗，中位总生存期达到了18.5个月；而仅仅接受免疫治疗的患者中位总生存期是10.8个月，整整提高了近8个月的时间，可将患者死亡风险降低约37%（HR=0.63）。然而，市场并不买账。当天，Novocure股价接近腰斩，其中国合作伙伴再鼎医药股价同样大跌。深究其中根源或许在于LUNAR的临床设计并不完美：该临床试验所选取的对照组主要为化疗，免疫疗法群体占比只有31%，而如今PD-1联合化疗已成为驱动基因阴性NSCLC的一线治疗手段。也就是说，LUNAR并没有充分的数据，证明其作为联用治疗方式，优于最新的标准疗法。另外，还有一个潜在的原因：此前市场对这一临床结果抱有极高的期待。2021年4月13日，美国独立数据监察委员会（DMC）在对研究进行中期分析报告审查后，建议研究样本量减少将近一半并将随访时间缩短至12个月，当天Novocure上涨49%，再鼎医药上涨22%；2023年1月，Novocure和再鼎医药共同宣布LUNAR研究达到了主要终点生存期，OS数据在统计学上具有显著且有临床意义的改善。当天Novocure上涨68%，再鼎上涨41%。LUNAR研究中虽然中位OS达到主要终点，但无进展生存（PFS）数据并不亮眼，两组之间的PFS相差无几（4.8个月 vs. 4.1个月），数据改善显然还是没有达到大家的期望。基于其临床设计瑕疵以及部分结果，市场担忧该产品是否将会获得FDA通过。 LUNAR研究简介（图片出自Novocure官网） TTFields未来路在何方？虽然目前TTFields的适应症拓展之路仍崎岖不平、迷雾重重，但笔者相信只要其找准方向积极探索，终能拨开迷雾见月明。卵巢癌方面，Ш期临床OS虽未达到主要终点，但后续仍有机会通过对该临床试验数据的全面分析，精准筛选出获益人群，得到阳性结果。非小细胞肺癌方面，LUNAR临床研究数据仍有望作为2023年下半年向美国FDA提交上市前批准（PMA）的基础。再鼎医药计划在Novocure向FDA递交申请后，向中国国家药品监督管理局（NMPA）提交上市许可申请（MAA）。2020年，TTF销售额高达5亿美元，主要收入来源胶质母细胞瘤适应症。一直以来肿瘤界便有"得肺癌者得天下"的说法，如果肺癌适应症获批上市，意味着TTF适用人群放大到最大癌种，TTF的天花板将进一步打开，未来市场将成指数级增长，肿瘤电场治疗成为"印钞机"将是必然事件。另外LUNAR临床数据的公布，进一步证实了TTFields具有对PD-1治疗增敏的可能，至于联合免疫究竟疗效如何，还需要更多研究证实。目前已有几项探索TTFields联合免疫疗法的临床试验已在进行中。早在2021年，默沙东就开展了K药联合TTFields一线治疗非小细胞癌的KeyNote-B36研究。如果这一研究能得出积极的结果，对TTFields无异于将是柳暗花明又一村。此外TTFields联合免疫/化疗一线治疗晚期驱动基因阴性NSCLC的LUNAR2研究已经在计划启动中，未来这些研究或许可以给出更多答案。除此之外，TTFields在多种消化道肿瘤中已完成或正在开展多项临床研究。例如，在胰腺癌治疗的PANOVA研究中，TTFields联合化疗可显著延长中位无进展生存（mPFS）和中位总生存（mOS），且具有良好的依从性和安全性，目前，CSCO指南已将TTFields作为局晚期和转移性胰腺癌的治疗选择推荐；此外，PANOVA-3研究（随机、开放标签的全球关键Ⅲ期研究）也已经顺利启动，目前正在入组当中，非常令人期待。在肝癌治疗中，Ⅱ期HEPANOVA研究显示，TTFields联合索拉非尼治疗的ORR约为索拉非尼单药的两倍，安全性可控。目前已有基础研究提示，TTFields联合化疗用于肠癌具有协同增效作用，期待后续临床研究的进展。联合疗法方面，除了联合免疫疗法，TTFields无论联合放疗还是血管靶向治疗都显示出令人鼓舞的初步疗效和可耐受的安全性，值得进一步深入探索。参考来源 1. Novocure Announces Update on Phase 3Pivotal LUNAR Trial of Tumor Treating Fields in Non-Small Cell Lung Cancer.Retrieved April 13, 2021, fromhttps://www.businesswire.com/news/home/20210413005428/en.Gregory F. Guzauskas, Erqi L. Pollom,Volker W. Stieber, Bruce C. 2. Wang, Lou Garrison. Tumor treating fieldstreatment for patients with newly diagnosed glioblastoma: A cost-effectivenessanalysis [abstract]. In: Proceedings of the American Association for CancerResearch Annual Meeting 2018 3. Novocure公司官网智药研习社近期直播报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

财报临床3期上市批准申请上市

2022-07-13

·BioSpace

FDA Grants Orphan Drug Designation (ODD) Status to NeoImmuneTech's NT-I7 for the treatment of Glioblastoma Multiforme

Glioblastoma multiforme is one of the most complex, deadly and treatment-resistant cancer with a 5-year survival rate of 6.8% and an average length of survival of only 8 months [1] FDA ODD designation bolsters NeoImmuneTech's determination to accelerate the clinical development of NT-I7 as a potential new therapy for this difficult-to-treat cancer ROCKVILLE, Md, July 13, 2022 /PRNewswire/ -- NeoImmuneTech, Inc. (NIT), a T cell-focused therapeutics company, today announced that the U.S. Food and Drug Administration (FDA) has granted NT-I7 (efineptakin alfa) (rhIL-7-hyFc) Orphan Drug Designation for the treatment of Glioblastoma Multiforme. Despite decades of research, GBM remains one of the deadliest and hardest-to-treat cancers. More than 13,000 Americans are expected to be diagnosed with GBM in 2022.1 Standard treatments using surgery, radiation, TMZ and TTFs have failed to date to greatly improve survival, and there is no standard treatment for recurrence, which is inevitable. Also, among the multiple factors impacting the survival of GBM patients, the current treatment options expose patients to a severe and prolonged systemic lymphopenic state known as "treatment-related lymphopenia" (TRL). TRL is associated with shorter survival both in GBM and other solid tumors. With its potential to restore lymphocyte levels and subsequently reverse systemic lymphopenia, NT-I7 may offer promising ways to effectively treat GBM, if confirmed by its development program. Dr Se Hwan Yang, Ph.D., President and Chief Executive Officer of NeoImmuneTech, Inc. said: "We are excited that the FDA granted NT–I7 an ODD in the treatment of glioblastoma multiforme. This decision adds further credibility to our existing clinical evidence that NT-I7 has the potential to bring a new essential therapy option to people with advanced/metastatic GBM who have undergone prior chemo-radiation therapy. We look forward to continuing our collaboration with FDA, as we explore the benefits of NT-I7 in treating people with GBM in combination with other anti-cancer treatments, including immunotherapies". NT-I7 has been studied in several robust phase I and II clinical trials and has demonstrated the potential to amplify T cells across the subsets, boost the immune system, and prolong the anti-tumor response in people with GBM and other solid tumors.[2] Current studies in GBM include study NIT-107 in newly diagnosed GBM patients and study NIT-120 in recurrent GBM patients. Preliminary data from study NIT-107 presented at Society for Immunotherapy of Cancer Annual Meeting (SITC), in November 2021, showed favorable trends of progression free survival (PFS) and overall survival (OS) in NT-I7 treated high-grade gliomas (HGG) patients after chemoradiotherapy.[3] The FDA grants ODD status to medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US. Receiving ODD may help to expedite and reduce the cost of development, approval, and commercialization of a therapeutic agent (FDA filing fee waive, guaranteed sales period after approval, etc). About Glioblastoma Multiforme Glioblastoma multiforme, also referred to as a grade IV astrocytoma, is a fast-growing and aggressive brain tumor, which accounts for 49.1% of all primary malignant brain tumors. Each year, an estimate of more than 10,000 individuals in the United States succumb to GBM. Due to its characteristics of being difficult to treat and treatment-resistant cancer, the survival rates and mortality statistics or GBM have been virtually unchanged for decades. In addition to being life-threatening, the treatment is known to be harsh, inflicting devastating results to the brain, which controls cognition, mood, behavior and every function of every organ and body parts. It leaves many patients with inability to work, drive and host of other functions that contribute to one's sense of self and independence.1 About NT-I7 (efineptakin alfa) (rhIL-7-hyFc) NT-I7 (efineptakin alfa) is the only clinical-stage long-acting human IL-7, and is being developed in oncologic and immunologic indications, where T cell amplification and increased functionality may provide clinical benefit. IL-7 is a fundamental cytokine for naïve and memory T cell development and for sustaining immune response to chronic antigens (as in cancer) or foreign antigens (as in infectious diseases). NT-I7 exhibits favorable PK/PD and safety pro making it an ideal combination partner. NT-I7 is being studied in multiple clinical trials in solid tumors and as vaccine adjuvant. Studies are being planned for testing in hematologic malignancies, additional solid tumors and other immunology-focused indications. About NeoImmuneTech, Inc. NeoImmuneTech, Inc. (NIT) is a clinical-stage T cell-focused biopharmaceutical company, dedicated to expanding the horizon of immuno-oncology and enhancing immunity to infectious diseases. NIT is led by the scientific founder and inventor of NT-I7 (efineptakin alfa) and has a strong executive team with rich industry experience. NIT is expanding rapidly in personnel and operations, as well as partnering with industry and academic leaders to investigate NT-I7 as monotherapy and in combination with various immunotherapeutics. For more information, please visit . Forward-looking Statements The statements contained herein may contain certain forward-looking statements relating to NeoImmuneTech, Inc. (the "Company") that are based on its beliefs and expectations about the future. These forward-looking statements are based on a number of assumptions about the future, some of which are beyond the Company's control and are not a guarantee of future performance or developments. Such forward-looking statements are subject to certain risks and uncertainties that could cause actual results to differ materially from those contemplated by the relevant forward-looking statements. The Company does not undertake any obligation to update any forward-looking statements to reflect events that occur or circumstances that arise after the date of these documents. Accordingly, you should not place reliance on any forward-looking information or statements contained herein. Some of the data contained in these documents were obtained from various external sources, and the Company has not independently verified such data. Accordingly, the Company makes no representations as to the accuracy or completeness of the data, and such data involves risks and uncertainties, and is subject to change based on various factors. [1] National Brain Tumor Society 'Glioblastoma Facts and Figures' About GBM - GBM Awareness Day | National Brain Tumor Society Last accessed: June 2022 [2] Naing A, Kim R, Barve M, et all. Preliminary biomarker and clinical data of a phase 2a study of NT-I7, a long-acting interleukin-7, plus pembrolizumab: cohort of subjects with checkpoint inhibitor-naïve advanced pancreatic cancer Journal for ImmunoTherapy of Cancer 2021;9: [3] Zhou, Alice, et al. NT-I7, a long-acting interleukin-7, promotes expansion of CD8 T cells and NK cells and immune activation in patients with newly diagnosed high-grade gliomas after chemoradiation. J Immunother Cancer 2021;9(Suppl 2):A428 View original content: SOURCE The NeoImmuneTech, Inc

合作孤儿药疫苗免疫疗法放射疗法

100 项与 tTF-NGR(University of Münster) 相关的药物交易

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10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
淋巴瘤	临床1期	-	University of Münster	-

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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


NCT02902237 (CTgov)	临床1期	恶性实体肿瘤 \| 淋巴瘤	24	tTF-NGR	憲襯構繭廠範鏇壓憲蓋(醖憲膚繭廠鹹繭選淵憲) = 積襯艱積糧願網鹹築鑰窪範簾觸夢鬱鹽顧製糧 (觸範艱艱範築選憲淵鹹, 簾鹽積蓋網築積襯鏇蓋 ~ 餘廠簾觸壓壓壓選築憲) 更多	-	2020-12-08
NCT02902237 (ESMO2020)	临床1期	肿瘤	17	tTF-NGR	願夢簾膚憲鬱窪餘醖艱(廠膚範襯憲襯艱簾醖廠) = Isolated Troponin T hs elevation occurred as DLT and was interpreted as sensitive early sign for myocardial cell hypoxia, valuable for prevention of clinically relevant side effects. 遞網鏇膚蓋襯膚範衊範 (鬱憲鹹醖廠構蓋壓遞膚 ) 更多	-	2020-09-17
NCT02902237 (Pubmed \| Cancers (Basel)) 人工标引	临床1期	肿瘤	17	tTF-NGR	選鹹繭製願窪糧夢衊願(鏇觸膚夢獵淵衊艱襯齋) = solated and reversible elevation of high sensitivity (hs) Troponin T hs without clinical sequelae 壓窪築襯鑰鏇鏇繭壓醖 (構築鹹顧製餘醖窪餘憲 ) 更多	积极	2020-06-07