The purpose of this study, a single-center, open, single-dose clinical study, was to evaluate the safety, tolerability, and pharmacokinetic profile of IM83 CAR-T cells in the treatment of patients with relapsed or refractory osteosarcoma

开始日期2024-06-15

申办/合作机构

北京艺妙神州医药科技有限公司初创企业

[+1]

NCT05400603

/ Recruiting临床1期IIT

A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory/ Relapsed, or Progressive Neuroblastoma or Refractory/ Relapsed Osteosarcoma

The goal of this clinical trial is to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate in children with refractory or recurrent neuroblastoma or refractory/ relapsed osteosarcoma as well as to define the toxicities of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate

开始日期2023-11-06

申办/合作机构

Emory University

NCT05830123

/ Recruiting临床2期

ARTEMIS-002: A Phase 2, Multicenter, Open-label Study of Intravenous Administration of HS-20093 in Patients With Relapsed or Refractory Osteosarcoma and Other Sarcomas

HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells.
This is a phase 2, open-label, multi-center study to evaluate the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HS-20093 as a monotherapy in patients with relapsed or refractory osteosarcoma and other sarcomas.

开始日期2023-06-08

申办/合作机构

上海翰森生物医药科技有限公司

100 项与难治性骨肉瘤相关的临床结果

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0 项与难治性骨肉瘤相关的专利（医药）

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项与难治性骨肉瘤相关的文献（医药）

2025-01-01·American Journal of Physiology-Cell Physiology

The contribution of the novel CLTC-VMP1 fusion gene to autophagy regulation and energy metabolism in cisplatin-resistant osteosarcoma

Article

作者: Deng, Zhi ; Zou, Pingan ; Yang, Zhengxu ; Chen, Qincan ; Tao, Zhiwei ; Xiong, Tao

This study identifies the CLTC-VMP1 gene fusion as a key driver of chemotherapy resistance in osteosarcoma by regulating autophagy and reprogramming cellular energy metabolism. Through single-cell transcriptomics, the research reveals the heterogeneity of tumor cells and the role of VMP1 in promoting resistance to cisplatin. The findings suggest that targeting the CLTC-VMP1 fusion gene may offer new therapeutic strategies to overcome chemotherapy resistance in osteosarcoma.

2025-01-01·Phytomedicine

Decoding the role of SLC25A5 in osteosarcoma drug resistance and CD8+ T cell exhaustion: The therapeutic potential of phyllanthin

Article

作者: Wu, Yupeng ; Tang, Ning ; Wu, Xin ; Xiong, Jianbin ; Zhao, Qiangqiang ; Deng, Woding ; Deng, Zhixuan

Osteosarcoma is an aggressive malignant bone tumor with an obscure etiology, as well as high prevalence and poor prognosis in children and adolescents. We aimed to investigate the pathogenesis of osteosarcoma through a comprehensive analysis of the tumor immune microenvironment (TIME) using multiple single-cell RNA sequencing datasets. SLC25A5, a gene implicated in cellular aging, significantly influenced osteosarcoma development by altering the TIME and promoting CD8+ T cell exhaustion, which contributed to reduced chemosensitivity. Experimental validation demonstrated that SLC25A5 enhanced the proliferative, migratory, invasive, and osteolytic properties of drug-resistant osteosarcoma cells while reducing apoptosis, intensifying cisplatin resistance. Phyllanthin inhibited the malignant phenotype of cisplatin-resistant osteosarcoma cells and enhanced their sensitivity to cisplatin by suppressing SLC25A5 expression. This study highlights a novel pathogenic role of SLC25A5 in osteosarcoma and presents Phyllanthin as a promising therapeutic agent. Our study offers a pioneering exploration of the single-cell spatiotemporal evolution of osteosarcoma and identifies SLC25A5 as a critical factor in drug resistance and immune evasion. By integrating advanced single-cell technologies and functional assays, we provided novel insights into the molecular mechanisms underlying osteosarcoma progression and treatment resistance, facilitating innovative therapeutic strategies.

2024-12-01·JAMA Oncology

Lenvatinib Plus Ifosfamide and Etoposide in Children and Young Adults With Relapsed Osteosarcoma

Article

作者: Morgenstern, Daniel A. ; Meazza, Cristina ; Gambart, Marion ; Rubin, Elyssa ; Aerts, Isabelle ; Campbell, Martin ; Howell, Lisa ; Kim, AeRang ; Campbell-Hewson, Quentin ; Martin-Broto, Javier ; Bautista, Francisco ; Borinstein, Scott ; McCabe, Martin G. ; Morland, Bruce ; Dela Cruz, Filemon S. ; Ahlström, Marie ; Yen Soh, Shui ; Hung, Giun-Yi ; Benadiba, Joy ; Yeoh, Allen ; Strauss, Sandra J. ; Lowis, Stephen ; Amoroso, Loredana ; Glade Bender, Julia L. ; Pressey, Joseph ; Leavey, Patrick ; Cost, Carrye ; Lervat, Cyril ; Loong, Herbert ; Sastre Urgelles, Ana ; Vo, Kieuhoa ; Mudry, Petr ; Korenbaum, Clement ; Zapotocky, Michal ; Jin Kang, Hyoung ; Collier, Anderson ; Ek, Torben ; Ronghe, Milind ; De Wilde, Bram ; Chan, Godfrey Chi-Fung ; Huang, Jie ; Vallance, Kelly ; Cuzzubbo, Daniela ; Lee (Previous PI: Giun Yi Hung), Chih-Ying ; Juan Ribelles, Antonio ; Janeway, Katherine A. ; Jung (Previous PI: Hyo Song Kim), Minkyu ; Gros Subias, Luis ; Locatelli, Franco ; Gaspar, Nathalie ; Okpara, Chinyere E. ; Won Lee, Ji ; McCowage, Geoffrey ; Márquez Vega, Catalina ; Makin, Guy ; Nicholls, Wayne ; Longhi, Alessandra ; Tabone, Marie-Dominique ; Gerber, Nicolas U. ; Farid Harunal Rashid, Mohamad ; Garraus Oneca, Moira ; Diezi, Manuel ; Bidadi, Behzad ; Jou, Shiann-Tarng ; Phillips, Marianne ; Entz-Werle, Natacha ; Philips, Robert ; Bear, Melissa ; Offer, Katharine ; Rubio San Simon (previous PI: Francisco Jose Bautista), Alba ; Whittle, Sarah B. ; Kheradpour, Albert ; Wilson, Shaun ; Baecklund, Fredrik ; McKenzie, Jodi ; Capra, Michael ; Verite, Cecile ; Cleirec, Morgane ; van Eijkelenburg, Natasha ; Koh, Kyung-Nam ; Mansuy, Ludovic ; Palmu, Sauli ; Bhadri, Vivek ; Lee, Jun Ah ; Amar Yacobi, Shirah ; Winstanley, Mark ; Friedman, Gregory ; Kager, Leo ; Lopez Almaraz, Ricardo ; Verschuur, Arnauld

ImportanceThe combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.ObjectiveTo evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.Design, Setting, and ParticipantsThe OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), and 1 to 2 prior lines of systemic treatment. The data analyses were performed between March 22, 2020 (first patient in) and June 22, 2022 (data cutoff for the primary analysis), and September 29, 2023 (end of study final database lock).InterventionsThe OLIE trial assessed the efficacy and safety of lenvatinib (14 mg/m2 taken orally once daily) combined with up to 5 cycles of ifosfamide (3000 mg/m2 intravenously) and etoposide (100 mg/m2 intravenously) on days 1 to 3 of each cycle vs IE alone at the same doses. Patients randomized to IE could cross over to receive lenvatinib upon disease progression by independent imaging review.Main Outcomes and MeasuresThe primary end point was progression-free survival (PFS) per RECIST 1.1 by independent imaging review. The Kaplan-Meier method was used to estimate the PFS distribution, with a prespecified 1-sided significance threshold of .025 by stratified log-rank test. Secondary end points included PFS rate at 4 months and overall survival. Adverse events were summarized using descriptive statistics.ResultsA total of 81 patients were enrolled (median [IQR] age, 15.0 [12.0-18.0] years; 46 males [56.8%]), with 40 in the LEN-IE arm and 41 in the IE arm. Median PFS was 6.5 months (95% CI, 5.7-8.2 months) for the LEN-IE arm and 5.5 months (95% CI, 2.9-6.5 months) for the IE arm (hazard ratio [HR], 0.54; 95% CI, 0.27-1.08; 1-sided P = .04). The rate of PFS at 4 months was 76.3% (95% CI, 59.3%-86.9%) in the LEN-IE arm and 66.0% (95% CI, 47.7%-79.2%) in the IE arm. Median overall survival was 11.9 months (95% CI, 10.1 months to not estimable) with LEN-IE and 17.4 months (95% CI, 14.2 months to not estimable) with IE (HR, 1.28; 95% CI, 0.60-2.70; 1-sided nominal P = .75). Grade 3 or higher treatment-related adverse events occurred in 35 of 39 patients (89.7%) in the LEN-IE arm and 31 of 39 patients (79.5%) in the IE arm.Conclusions and RelevanceAlthough LEN-IE did not meet prespecified statistical significance for improved PFS vs IE, this study demonstrates the importance of international collaboration and randomized clinical trials in patients with relapsed or refractory osteosarcoma and may inform future trial design.Trial RegistrationClinicalTrials.gov Identifier: NCT04154189

项与难治性骨肉瘤相关的新闻（医药）

2025-01-10

·癌度

《癌度早报2025年1月10日》

一、新药快讯 1、节拍化疗联合内分泌治疗激素受体阳性乳腺癌 2025年1月2日，中山大学肿瘤防治中心王树森教授领衔的一项研究刊登在《临床肿瘤学杂志》，研究结果表明，节拍化疗药物卡培他滨联合芳香化酶抑制剂，能够显著延长激素受体阳性乳腺癌患者的无进展生存期，中位总生存时间也获得了延长，这个研究未那些CDK4/6抑制剂不能耐受的乳腺癌患者提供了新的治疗选择。 2、针对B7-H3的抗体偶联药，获得美国FDA突破性疗法认定近日，美国食品药品监督管理局FDA授予新型抗体偶联药GSK5764227突破性疗法资格认定，这款抗体偶联药是针对B7-H3这个靶点，在许多癌症中，B7-H3靶点都会显著上升，癌细胞可以借助它们成功躲避免疫系统的剿灭，相应的临床试验证据表明，在11名晚期小细胞肺癌患者中，7人肿瘤大幅缩小或消失，如果加上肿瘤保持稳定的患者，则总体疾病控制率达到81.8%。此外，该药在难治性骨肉瘤患者中展现了充满希望的抗肿瘤活性和可控的安全性。 3、雷替凡利单抗治疗HPV引起的肛管鳞状细胞癌，56%的患者病灶缩小 HPV病毒不仅仅会引起宫颈癌，还会引发其他部位的癌症，比如肛管鳞状细胞癌，雷替凡利单抗是一种靶向PD-1的免疫治疗药物，在一项三期临床试验中，常规化疗卡铂联合紫杉醇和雷替凡利单抗，有56%的患者可评估肿瘤病灶缩小，而使用单独化疗的患者组仅有44%的患者病灶大幅度缩小。此外雷替凡利单抗联合化疗的中位总生存时间为29.2个月，而单独化疗组的中位总生存时间是23个月。二、新药快讯 1、自身免疫疾病患者，能不能使用免疫治疗？最近，一项包括2万5千名患有自身免疫疾病的肿瘤患者使用免疫药物的研究被公布，这些患者包括皮肤癌、肺癌、胃肠道肿瘤和泌尿系统肿瘤，他们接受了PD-1或PD-L1抑制剂治疗，研究的结果表明，如果这些患者能够将自身免疫疾病控制好，那么也可以从免疫治疗药物里获益，而且不会增加风险。但具体临床用药时仍然需要结合病情由主治医生来判断。

免疫疗法快速通道突破性疗法临床3期

2025-01-08

·翰森制药

翰森制药HS-20093再获FDA突破性疗法认定，用于后线复发或难治性骨肉瘤治疗

- HS-20093/GSK'227再获FDA突破性疗法认定，用于后线复发或难治性骨肉瘤治- -这是HS-20093/GSK'227在中、美、欧斩获的第四项监管认定，也是FDA授予HS-20093/GSK'227的第二项突破性疗法认定 -对于既往二线经治后进展的骨肉瘤患者，目前尚无获得FDA批准的治疗方法。 2025年1月7日，翰森制药集团有限公司（以下简称“翰森制药”，03692.HK），中国领先的创新驱动型制药企业宣布，合作方葛兰素史克（GSK）就GSK5764227(GSK'227,亦称HS-20093)获得美国食品药品监督管理局（FDA）授予的突破性疗法认定（BTD）。该药物为B7-H3靶向抗体药物偶联物（ADC），正在评估用于治疗既往经二线及以上治疗进展的晚期复发或难治性骨肉瘤（骨癌）成人患者。本次FDA突破性疗法认定得到了翰森制药正在推进的ARTEMIS-002研究数据的支持。这是一项正在进行的Ⅱ期、开放标签、随机、多中心临床试验，评估HS-20093/GSK'227在复发或难治性骨肉瘤及其他不可切除的骨和软组织肉瘤患者中的有效性和安全性。该试验共纳入了60多名患者，其中42名患有骨肉瘤。ARTEMIS-002的结果已在2024年美国临床肿瘤学会（ASCO）年会上展示。近期，GSK开始了一项全球Ⅰ期临床试验，以支持GSK'227的注册性研究。这是HS-20093/GSK'227斩获的第四项监管认定，此前HS-20093/GSK'227已在中、美、欧分别获得监管认定，具体信息如下。 2024年8月美国食品药品监督管理局（FDA）授予GSK'227突破性疗法认定，用于含铂化疗期间或之后进展的（复发或难治性）广泛期小细胞肺癌（ES-SCLC）患者治疗。 2024年11月中国国家药品监督管理局（NMPA）将HS-20093纳入突破性治疗药物，拟定适应症为经标准一线治疗（含铂双药化疗联合免疫）后进展的广泛期小细胞肺癌（ES-SCLC）。 2024年12月欧洲药品管理局 (EMA)授予 GSK'227优先药物（PRIME）认定，用于复发广泛期小细胞肺癌（ES-SCLC）患者的治疗。 HS-20093(GSK'227)是一种新型B7-H3靶向抗体药物偶联物(ADC)，由全人源抗B7-H3单抗与拓扑异构酶抑制剂(TOPOi)有效载荷共价连接而成，目前正在中国开展用于治疗肺癌、肉瘤、头颈癌以及其他实体瘤的多项I期、II期及III期临床研究。2023年12月20日，翰森制药与GSK订立独家许可协议，授予GSK全球独占许可（不含中国内地、香港、澳门及台湾），以开发、生产及商业化HS-20093(GSK'227)。骨肉瘤主要影响儿童和年轻成人，是最常见的原发性骨癌，占所有骨癌的20-40%。1它是一种罕见的疾病，在美国每年每百万人中有3.3名患者，占所有新癌症诊断的不到1%。2,3大约20-30%的局部（非转移性）骨肉瘤患者和80%的转移性骨肉瘤患者经历复发或难治性疾病。4在接受一线化疗后，复发或难治性骨肉瘤患者的治疗选择非常有限，没有明确的护理标准。5对于既往二线经治后进展的骨肉瘤患者，目前尚无获得美国食品药品监督管理局（FDA）批准的治疗方法。翰森制药是中国领先的创新驱动型制药企业，重点关注抗肿瘤、抗感染、中枢神经系统、代谢及自身免疫等重大疾病治疗领域，致力于通过持续创新提高人类生命质量。截至目前，翰森制药已上市7款创新药，形成了丰富的产品管线。翰森制药连续多年位居全球制药企业百强、中国医药研发产品线最佳工业企业前3强，是国家重点高新技术企业、国家技术创新示范企业。翰森制药于2019年6月在香港联交所挂牌上市（股票代码：03692.HK）。参考文献： 1.Valery PC, Laversanne M, Bray F. Bone cancer incidence by morphological subtype: a global assessment. Cancer Causes Control. 2015;26(8):1127-39. 2.Cole S, Gianferante DM, Zhu B, et al. Osteosarcoma: A surveillance, epidemiology, and end results program-based analysis from 1975 to 2017. Cancer. 2022;128(11):2107-18. 3.Mirabello L, Troisi RJ, Savage SA. International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer. 2009;125(1):229-34. 4.Durfee RA, Mohammed M, Luu HH. Review of Osteosarcoma and Current Management. Rheumatol Ther. 2016 Dec;3(2):221-243. doi: 10.1007/s40744-016-0046-y. Epub 2016 Oct 19. PMID: 27761754; PMCID: PMC5127970. 5.National Comprehensive Cancer Network (NCCN). NCCN clinical practice guidelines in oncology (NCCN Guidelines): bone cancer. August 20, 2024. Version 1.2025. Accessed 24 October 2024.https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf 内容来源于网络，如有侵权，请联系删除。

突破性疗法ASCO会议抗体药物偶联物引进/卖出

2025-01-08

·Pharmaceutical Technology

FDA awards GSK breakthrough status for relapsed osteosarcoma treatment

Predominantly affecting children and young adults, osteosarcoma represents the most widespread primary bone cancer. Credit: Anciens Huang/Shutterstock. GSK has gained US Food and Drug Administration (FDA) breakthrough therapy designation (BTD) for its B7-H3-targeted antibody-drug conjugate (ADC), GSK’227, to treat adults with relapsed or refractory osteosarcoma who have progressed on a minimum of two previous lines of therapy. This marks the third regulatory milestone for the therapy. The BTD is backed by data from the randomised, multi-centre Phase II ARTEMIS-002 trial assessing the safety and efficacy of the therapy in subjects with this condition and other unresectable bone and soft tissue sarcomas. Conducted by China-based pharmaceutical company Hansoh Pharma, the trial enrolled more than 60 subjects, along with 42 osteosarcoma subjects. GSK oncology research and development global head and senior vice-president Hesham Abdullah stated: “This latest regulatory designation for GSK’227 exemplifies the potential of our targeted ADC in patients with difficult to treat cancers. “For patients with relapsed or refractory osteosarcoma, there is an urgent unmet medical need with no approved treatment options once the cancer returns, and chemotherapy provides limited benefit in this setting.” GSK acquired exclusive global rights, excluding mainland China Macau, Taiwan and Hong Kong, to the therapy from Hansoh Pharma in 2024. The acquisition allows GSK to clinically develop and commercialise GSK’227 further globally clinically. The company has recently initiated a global Phase I trial as part of the development plan to support the therapy’s registrational pathway. Predominantly affecting children and young adults, osteosarcoma is the most widespread primary bone cancer. Also known as HS-20093, GSK’227 is a fully human anti-B7-H3 monoclonal antibody linked covalently to a topoisomerase inhibitor payload. In November 2024, GSK received Japan’s Ministry of Health, Labour and Welfare’s approval to extend the indication of its respiratory syncytial virus (RSV) vaccine, Arexvy, to include individuals aged 50 to 59 at increased risk.

临床结果临床2期抗体药物偶联物临床1期突破性疗法