A Phase 1/2, Open-Label Study to Investigate the Safety and Efficacy of Membrane Bound IL15 Expressing Tumor-Infiltrating Lymphocytes (OBX-115) In Participants With Advanced Solid Tumors

This is a study to investigate the safety and efficacy of an investigational OBX-115 regimen in adult participants with advanced solid tumors.

开始日期2023-10-25

申办/合作机构

Obsidian Therapeutics, Inc.

NCT05470283

/ Active, not recruiting临床1期IIT

Phase I, Open-Label, Study of Tumor Infiltrating Lymphocytes Engineered With Membrane Bound IL15 Plus Acetazolamide in Adult Patients With Metastatic Melanoma

The goal of this clinical research study is to find the recommended dose of OBX-115 in combination with acetazolamide that can be given to patients with metastatic melanoma previously treated with immune checkpoint inhibitors. The safety and tolerability of the study drug combination will also be studied.

开始日期2022-09-07

申办/合作机构

The University of Texas MD Anderson Cancer Center

100 项与 OBX-115 相关的临床结果

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100 项与 OBX-115 相关的转化医学

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100 项与 OBX-115 相关的专利（医药）

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项与 OBX-115 相关的文献（医药）

2025-04-01·MOLECULAR THERAPY

IL-2-independent expansion, persistence, and antitumor activity in TIL expressing regulatable membrane-bound IL-15

Article

作者: Burga, Rachel A ; Sethi, Dhruv K ; Sun, Dexue ; Kulkarni, Gauri S ; Pedro, Kyle D ; Young, Violet A ; Primack, Benjamin ; Ter Meulen, Jan ; Ross, Theresa ; Ao, Zheng ; Tremblay, Jack Ryan ; Khattar, Mithun ; Subramanian, Shyam ; Ols, Michelle ; Aksoy, Bulent Arman ; Li, Dan Jun ; Tchaicha, Jeremy H ; Lajoie, Scott ; Villasmil Ocando, Alonso ; Langley, Meghan

Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) has demonstrated great potential for patients with treatment-refractory metastatic melanoma. However, the need for interleukin-2 (IL-2) co-administration during TIL cell therapy limits patient eligibility and restricts treatment to intensive care units due to the risk of severe side effects. Instead, engineering TIL with membrane-bound interleukin-15 (mbIL15) has the potential to promote TIL expansion, antitumor activity, and persistence of CD8+ T cells, without the use of IL-2. cytoTIL15 cells express mbIL15 fused to a drug-responsive domain (DRD) that is regulated by the Food and Drug Administration-approved small-molecule drug acetazolamide (ACZ). As such, cytoTIL15 cells are manufactured with ACZ instead of IL-2, in the presence of engineered feeder cells. The cytoTIL15 cell product exhibits ACZ dose-dependent expansion and persistence in vitro and in vivo and potent tumor-killing activity in human melanoma models in the absence of IL-2. In patient-derived xenograft (PDX) tumors, spatial profiling revealed infiltrating cytoTIL15 cells to be highly cytotoxic and less exhausted than non-engineered TIL. This novel platform creates a powerful, IL-2-free TIL cell therapy with a potentially improved tolerability and safety profile, while allowing individualized pharmacologic regulation of the TIL product.

项与 OBX-115 相关的新闻（医药）

2025-05-15

·同写意

TIL疗法崛起：实体瘤治疗的“破局者”

细胞疗法免疫疗法临床2期

2025-04-25

·Business Wire

Obsidian Therapeutics Announces Multiple Presentations at the American Association for Cancer Research Annual Meeting

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Obsidian Therapeutics, Inc., a clinical-stage biotechnology company pioneering engineered cell and gene therapies, today announced the publication of 3 abstracts for poster presentations at the American Association for Cancer Research (AACR) Annual Meeting 2025. In addition to a trial-in-progress study design update on the ongoing multicenter study Agni-01 (NCT06060613), Obsidian will share preclinical data from our cytoDRiVE® platform demonstrating spatiotemporal regulation of membrane-bound IL12 in syngeneic solid tumor models and preclinical data on OBX-115 TIL phenotype starting from NSCLC tumor tissue. Obsidian is presenting new preclinical data from its cytoDRiVE regulation platform, further demonstrating the ability to unlock the therapeutic window of potent cytokines and broaden the reach of armored cell therapies. The poster for abstract LB025 demonstrates the application of Obsidian’s regulatable cytoDRiVE platform to enhance antigen-responsive (“spatial”) promoter-induced activation by adding a critical pharmacologically regulatable (“temporal”) signal to exert tight “spatiotemporal” control over IL12 expression1, resulting in a positive impact on safety and tumor control in syngeneic solid tumor models. Obsidian will also present preclinical data from a multimodal phenotyping analysis comparing OBX-115 TIL generated with its proprietary manufacturing process to conventional, non-engineered TIL using NSCLC tumor samples. The poster for abstract LB359 provides evidence that, as observed with melanoma2, the OBX-115 process generates a minimally exhausted, CD8+ enriched and memory “stem-like” T-cell phenotype. Additionally, the tumor reactive gene signature analysis showed that the drug product is enriched for putative tumor-reactive T-cell clonotypes. Obsidian Posters at AACR 2025: Spatiotemporally regulated expression of membrane-bound interleukin 12 (mbIL12) for armored adoptive cell therapy (ACT) shows strong antitumor activity in syngeneic solid tumor models without overt toxicity (Abstract LB025) Presenting Author: Ross T, Obsidian Therapeutics Poster: Sunday, April 27, 2:00-5:00pm CT Presenting Author: Ross T, Obsidian Therapeutics Poster: Sunday, April 27, 2:00-5:00pm CT OBX -115 TIL from non-small cell lung cancer (NSCLC) are enriched for putative tumor-reactive, stem-like T cells with enhanced tumor cytotoxicity: Results from multimodal phenotyping analysis (Abstract LB359) Presenting Authors: Schoenfeld AJ, Memorial Sloan Kettering Cancer Center Poster: Tuesday, April 29, 2:00-5:00pm CT Presenting Authors: Schoenfeld AJ, Memorial Sloan Kettering Cancer Center Poster: Tuesday, April 29, 2:00-5:00pm CT Trial in progress: Phase 1/2 study of OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy in patients with advanced solid tumors (Abstract CT244) Presenting Author: Shoushtari AN, Memorial Sloan Kettering Cancer Center Poster: Tuesday, April 29, 2:00-5:00pm CT Presenting Author: Shoushtari AN, Memorial Sloan Kettering Cancer Center Poster: Tuesday, April 29, 2:00-5:00pm CT 1 Smith et al., SITC 2024 (Abstract 463). 2 Bernatchez et al., ISCT 2024 (Abstract 909). About OBX-115 Obsidian’s lead investigational cytoTIL15™ program, OBX-115, is a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15). OBX-115 has the potential to become a meaningful therapeutic option for patients with advanced or metastatic melanoma and other solid tumors by leveraging the expected benefits of mbIL15 and Obsidian’s proprietary, differentiated manufacturing process to enhance persistence, antitumor activity, and clinical safety of TIL cell therapy. Obsidian is investigating OBX-115 in the phase 1/2 Agni-01 multicenter trial in patients with advanced solid tumors (NCT06060613). About Obsidian Therapeutics Obsidian Therapeutics, Inc. is a clinical-stage biotechnology company pioneering engineered cell and gene therapies to deliver transformative outcomes for patients with intractable diseases. Obsidian’s proprietary cytoDRiVE® technology is designed to precisely regulate the timing and level of protein function by using FDA-approved small-molecule drugs. Obsidian is headquartered in Cambridge, MA. For more information, please visit www.obsidiantx.com and follow us on LinkedIn.

细胞疗法AACR会议免疫疗法临床研究

2025-02-13

·求实药社

终止！TIL的黄金时代，还没开始就结束了？

Turnstone倒下，TIL细胞的未来何去何从？ 2月5日，细胞治疗领域传来一则意味深长的消息——2024年2月5日，Turnstone Biologics宣布终止其唯一临床阶段TIL管线TIDAL-01开发，距其2023年6月8000万美元IPO仅隔18个月。财务数据显示，公司截至2024年Q3现金储备4530万美元（SEC 10-Q文件），原计划资金可持续至2026年Q2。然而，连续的业务调整已暴露出公司运营的困境。事实上，Turnstone早在2022年秋季便经历了一轮裁员，彼时正值与艾伯维（AbbVie）和武田（Takeda）的合作终止。而在2024年10月，公司再次裁员约60%，试图集中资源押注TIDAL-01。如今，核心管线的终止无疑使其前景更加黯淡。尽管细胞治疗领域始终充满创新，TIL疗法的商业化进程却始终缓慢而艰难。Turnstone的退出，究竟是因为TIL技术本身仍不够成熟，还是整个赛道已开始降温？这一变局，值得行业深思。 TIL疗法商业化的“三座大山” 尽管TIL疗法在个性化细胞治疗领域具有潜力，但其在商业化落地方面仍面临诸多挑战：适应症受限：目前，Lifileucel仅获批用于黑色素瘤，而其他实体瘤适应症的开发进展缓慢。相比之下，CAR-T疗法已在血液瘤领域建立成熟的商业模式，TIL的适应症局限性使其市场天花板受限。生产和供应链难题：TIL治疗仍然是高度个体化的方式，每位患者的肿瘤浸润淋巴细胞需单独扩增，这导致生产周期长、成本高、供应链复杂，使大规模推广面临现实阻碍。 MNC投资缺乏，资金流向受限：目前，TIL疗法尚未吸引跨国制药公司（MNC）的广泛投资，市场资金主要来自Biotech公司，而这些公司的抗风险能力相对较弱。在资本市场环境趋冷的背景下，TIL企业的生存压力进一步加剧。尽管Iovance仍在积极推进TIL疗法，但其商业模式的可持续性仍有待时间检验。未来，TIL是否能突破当前困境，仍取决于技术创新、成本控制以及市场认可度的进一步提升。全球TIL竞逐战：商业化初现，挑战仍存（数据截至2024年12月，来源：ClinicalTrials.gov） Iovance Biotherapeutics是目前TIL疗法商业化的唯一玩家。其核心产品Lifileucel于2024年2月获得FDA加速批准，用于黑色素瘤治疗，成为全球首款商业化的TIL疗法。然而，在商业化初期，Lifileucel仍面临市场接受度和生产成本的挑战，公司也在积极推进其在非小细胞肺癌和子宫内膜癌等其他实体瘤适应症上的应用。 Instil Bio曾是TIL疗法领域的挑战者，核心产品包括ITIL-168（用于黑色素瘤）和ITIL-306（用于实体瘤）。然而，2022年底，公司因制造问题暂停了TIL临床试验，并进行了战略调整。当前，Instil Bio正在计划重启部分TIL项目，力图恢复进展。然而，资金问题和制造挑战依然是公司面临的关键难题，Instil Bio是否能够重新崛起，仍未可知。 Obsidian Therapeutics正在通过基因编辑技术改造TIL，核心产品为OBX-115（PD-1敲除TIL，用于黑色素瘤）。2023年10月，公司启动了I期临床试验，计划将OBX-115与BMS的PD-1抑制剂Opdivo联合使用，以期提高疗效。这一策略旨在通过基因改造增强TIL的治疗效果，进一步提升其在黑色素瘤等实体瘤中的疗效。 Adaptimmune正在实施TIL与TCR-T双管线策略，核心产品为TIL-TCR混合细胞疗法。2023年，公司宣布这一策略，旨在结合TIL和TCR-T的优势，以期提高实体瘤的疗效。然而，TIL疗法仍面临制造成本高和疗效提升等方面的挑战。国产TIL疗法稳步推进，技术差异化初现中国在TIL领域的研究较国际市场晚了几年，但近年来已有Biotech公司开始布局，主要以本土创新企业为主，部分公司正在推进TIL临床试验。沙砾生物成立于2019年，专注于肿瘤免疫细胞治疗，特别是TIL药物的研发。公司拥有多项核心技术平台，管线包括6款TIL药物，针对多种实体瘤。GT101是中国首个进入临床的TIL药物，现已进入2期临床，针对复发性宫颈癌。GT201是国内首款基因编辑型TIL药物，已获得CDE临床试验许可，显示出显著疗效。上海君赛生物成立于2019年，专注于TIL疗法与新药开发。公司开发的GC101和GC203两款TIL疗法已进入临床试验，展现出显著疗效。GC203为全球首款非病毒载体基因修饰TIL疗法，已获NMPA临床许可；GC101为全球首款无需清淋和IL-2注射的天然TIL药物，正进行II期临床试验。西比曼生物是一家全球性临床阶段生物制药公司，专注于癌症、炎症及免疫疾病的T细胞治疗。公司在TIL领域有布局，其C-TIL051用于治疗PD-1抗体难治或复发的晚期非小细胞肺癌，已获得FDA批准进入1期临床试验。卡替医疗专注于TIL领域，开发了“超强型TIL”技术，通过基因改造提升TIL细胞对实体瘤的治疗效果和自我扩增能力。其产品ScTIL210无需手术获取TIL细胞，而是从外周血分离肿瘤识别性T细胞，简化治疗过程。目前，相关临床研究已展现积极疗效和安全性。劲风生物专注于基于AI和生物信息技术开发新一代TIL细胞疗法，特别针对实体肿瘤。其AI驱动的TABR-BERT学习模型提高了T细胞与抗原的精准识别，为细胞免疫疗法提供新途径。公司已搭建新生抗原-TCR筛选平台和TIL-CMC技术平台，TIL疗法已进入美国临床I期，安全性和有效性数据良好，并与NCI、UCSD等顶尖研究机构合作。智瓴生物成立于2016年，专注于细胞免疫治疗，涵盖研发、生产和临床应用。其主要产品管线包括TIL药物、NK细胞药物和DNT药物，第一代TIL药物已完成晚期宫颈癌IIT研究，第二代TIL药物获得NMPA临床试验许可。第三代TIL及其他细胞产品正在七个实体瘤适应症中并行开发，致力于为不同实体瘤提供特异性强、安全性高的疗法。 TIL疗法前景展望 TIL疗法的未来仍充满潜力，可能会在多个方面实现突破。研究表明，TIL与PD-1抑制剂（如Keytruda、Opdivo）联合使用时，可能会带来更强的抗肿瘤效果。另外，AI和自动化技术有望优化生产过程，显著降低成本和生产周期，从而提升TIL疗法的商业化可行性。同时，更精确的筛选方法可能帮助发现更高效的TIL亚群，提高疗效。结束语短期内（1-3年），TIL市场前景不太乐观。尽管Iovance仍是唯一的商业化玩家，但其面临的挑战包括市场接受度、生产成本和适应症拓展等问题。中期（3-5年）关键在于技术突破，若生产工艺优化或联合疗法取得突破，TIL可能迎来新机遇。然而，若跨国公司依旧不投入，生物科技公司能否独立推动市场发展仍不确定。长期（5年以上），虽然TIL可能在某些特定适应症上找到稳定市场，未来仍充满不确定性。目前，资本、技术共同决定了TIL的命运。Turnstone的撤退无疑是一个警示信号，但TIL是否会就此沉寂，仍取决于行业接下来的探索方向。免责声明：文章内容仅供参考，不构成投资建议。投资者据此操作，风险自担, 关于对文中陈述、观点判断保持中立，不对所包含内容的准确性、可靠性或完整性提供任何明示或暗示的保证。请读者仅作参考，并请自行承担全部责任。本公众号发布的各类文章重在分享，如有侵权请联系我们，我们将会删除。联系我们 ABC 2025 展位火热预定中！扫码立即咨询电话：13816031174 （同微信）赞助形式包括但不仅限于演讲席位、会场展位、会刊彩页、晚宴赞助、会议用品宣传等。点击此处“阅读全文”咨询更多精彩！

细胞疗法加速审批免疫疗法IPO

100 项与 OBX-115 相关的药物交易

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研发状态

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
晚期恶性实体瘤	临床2期	美国	Obsidian Therapeutics, Inc.	2023-10-25
转移性肺癌	临床2期	美国	Obsidian Therapeutics, Inc.	2023-10-25
转移性黑色素瘤	临床2期	美国	Obsidian Therapeutics, Inc.	2023-10-25
转移性非小细胞肺癌	临床2期	美国	Obsidian Therapeutics, Inc.	2023-10-25
黑色素瘤	临床1期	-	Obsidian Therapeutics, Inc.	-
非小细胞肺癌	临床前	-	Obsidian Therapeutics, Inc.	2023-12-08
实体瘤	临床前	美国	Anderson University	-

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临床结果

适应症

分期

评价

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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


444 (SITC2024)	N/A	非小细胞肺癌	4	OBX-115 (Surgically resected tumor tissue)	簾築範範餘蓋鏇簾窪衊(繭範襯淵膚糧簾憲鹽獵) = 構遞醖鑰憲製淵壓構廠選製鑰範醖鏇積鹽願壓 (蓋築齋憲顧獵艱網構廠, 2.6) 更多	积极	2024-11-05
444 (SITC2024)	N/A	非小细胞肺癌	4	OBX-115 (Simulated core needle biopsy (sCNB) tumor tissue)	簾築範範餘蓋鏇簾窪衊(繭範襯淵膚糧簾憲鹽獵) = 網繭鬱獵鏇艱夢憲獵襯選製鑰範醖鏇積鹽願壓 (蓋築齋憲顧獵艱網構廠, 1.7) 更多	积极	2024-11-05
NCT05470283 (AACR2024) 人工标引	临床1期	转移性黑色素瘤	6	OBX-115 + ACZ 125 mg	憲鏇顧憲醖餘窪壓鬱齋(願鏇製鏇簾蓋鹽製醖積) = 鏇獵積鏇齋衊觸遞膚廠構鹹壓鬱憲淵淵壓積網 (齋廠淵醖衊網鹹構顧積 ) 更多	积极	2024-04-05
NCT05470283 (Biospace) 人工标引	临床1期	黑色素瘤	6	OBX-115	餘獵壓淵鹹鏇製遞鏇艱(憲襯壓鑰鑰製簾製膚網) = none 衊餘艱構襯壓顧淵醖獵 (願餘餘壓糧夢衊顧選獵 ) 更多	积极	2023-12-12