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）

2025-06-02

·PipelineReview

Obsidian Therapeutics Announces Positive Clinical Data from OBX-115 in Patients with Advanced Melanoma in Ongoing Multicenter Study at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting

CAMBRIDGE, MA, USA I June 02, 2025 I Obsidian Therapeutics, Inc. , a clinical-stage biotechnology company pioneering engineered cell and gene therapies, today announced initial Phase 1 safety and efficacy data from the Phase 1/2 Agni-01 multicenter study of OBX-115, a novel engineered tumor-derived autologous T cell immunotherapy (tumor-infiltrating lymphocyte [TIL] cell therapy) armored with pharmacologically regulatable membrane-bound IL15 (mbIL15), in patients with immune checkpoint inhibitor (ICI)-resistant advanced or metastatic melanoma ( NCT06060613 ). These data, summarized below, will be presented in a rapid oral presentation (abstract 9517) delivered by Jason A. Chesney, M.D., Ph.D., Director and Chief Administrative Officer of UofL Health – Brown Cancer Center/Oncology Service Line at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. Obsidian is also presenting a poster for abstract 9519 summarizing translational data from the Phase 1 first-in-human single-center study of OBX-115 ( NCT05470283 , enrollment completed) in ICI-resistant advanced melanoma. Summary of OBX-115 Safety and Efficacy Data (March 26, 2025 data cutoff): Advancing a More Patient-centric TIL Cell Therapy Regimen in Heavily Pre-treated Advanced Melanoma Patient Population OBX-115 Continues to Deliver Positively Differentiated Safety Profile Relative to Non-engineered TIL; No IL2, No Treatment-related Mortality: OBX-115 Maintains Consistent Efficacy Profile Without IL2 and With Low-dose Lymphodepletion in Anti-PD-1-resistant Advanced Melanoma; Dose Level 3 (RP2D) To Be Further Explored in Phase 2 Dr. Chesney commented, “It is very encouraging to see the promising safety and efficacy profile for OBX-115, now observed in the Agni-01 multicenter study. As a highly differentiated, IL2-sparing TIL cell therapy that is compatible with low-dose lymphodepletion, OBX-115 has the potential to transform the treatment landscape and broaden the eligible population for patients with high unmet need.” “The exciting results from OBX-115 in ICI-resistant advanced melanoma further indicate that OBX-115 has promising therapeutic potential, and that ACZ redosing is well-tolerated and has the potential to re-activate and re-expand persistent OBX-115 TIL,” commented Parameswaran Hari, M.D., Chief Development Officer of Obsidian. “We look forward to exploring the go-forward melanoma RP2D in Phase 2, and continuing to evaluate OBX-115 in a Phase 1 cohort of patients with advanced non-small cell lung cancer, where we believe the potential impact from an IL2-sparing TIL cell therapy is clinically significant and may expand patient eligibility.” Obsidian is actively enrolling patients with advanced or metastatic melanoma and non-small cell lung cancer (NSCLC) at multiple sites in its ongoing Phase 1/2 Agni-01 multicenter study. Additional details may be found at clinicaltrials.gov, using identifier: NCT06060613 . 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. SOURCE: Obsidian Therapeutics

临床1期免疫疗法细胞疗法ASCO会议基因疗法

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

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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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)	鏇範鹽範獵衊膚積廠願(簾獵膚餘繭醖顧鏇獵觸) = 網廠簾衊膚鹹醖鏇範鹽製鬱觸艱艱願憲鏇餘餘 (築壓範蓋簾鬱艱觸繭廠, 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)	鏇範鹽範獵衊膚積廠願(簾獵膚餘繭醖顧鏇獵觸) = 壓廠築餘顧獵廠遞蓋壓製鬱觸艱艱願憲鏇餘餘 (築壓範蓋簾鬱艱觸繭廠, 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	築觸構築廠繭鏇鬱鏇網(壓顧壓壓網餘製餘範鬱) = 齋積壓夢顧餘構醖選鑰構獵鑰鑰窪製範顧鑰醖 (艱淵廠選築觸遞淵鏇鹹 ) 更多	积极	2024-04-05
NCT05470283 (Biospace) 人工标引	临床1期	黑色素瘤	6	OBX-115	顧膚鏇顧簾窪窪壓壓窪(簾顧鬱襯構淵憲夢夢繭) = none 範願顧繭襯獵廠齋餘構 (願膚夢蓋鑰構願夢膚艱 ) 更多	积极	2023-12-12