TM-5614(TM-5614) - 药物靶点：PAI-1_在研适应症：费城染色体阳性慢性粒细胞白血病，骨软化，低磷血症佝偻病_专利_临床

A phase II investigator-initiated clinical trial of PAI-1 inhibitor (TM5614) for systemic sclerosis-associated interstitial lung disease under immunosuppressive treatment

开始日期2023-09-06

申办/合作机构-

JPRN-jRCT2031220084 / Not yet recruiting临床3期IIT

Phase 3, randomized, double-blind study of the efficacy of TM5614 in combination with tyrosine kinase inhibitors in chronic phase chronic myelogenous leukemia patients

开始日期2022-07-29

申办/合作机构-

JPRN-jRCTs031210704 / Recruiting临床2期IIT

Clinical trials investigating the efficacy and safety of TM5614 for congenital FGF23-related hypophosphatemic rickets / osteomalacia

开始日期2022-03-28

申办/合作机构-

100 项与 TM-5614 相关的临床结果

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100 项与 TM-5614 相关的转化医学

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100 项与 TM-5614 相关的专利（医药）

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10

项与 TM-5614 相关的文献（医药）

2024-10-17·British Journal of Dermatology

A phase II multicentre study of plasminogen activator inhibitor-1 inhibitor (TM5614) plus nivolumab for treating anti-programmed cell death 1 antibody-refractory malignant melanoma: TM5614-MM trial

Article

作者: Asano, Yoshihide ; Yoshino, Koji ; Yahata, Takashi ; Matsushita, Shigeto ; Fukushima, Satoshi ; Kato, Hiroshi ; Muto, Yusuke ; Otsuka, Atsushi ; Ishizuki, Shoichiro ; Amagai, Ryo ; Yamazaki, Emi ; Fujisawa, Yasuhiro ; Fujimura, Taku ; Kambayashi, Yumi ; Miyata, Toshio

AbstractBackgroundAnti-programmed cell death 1 antibodies (PD-1 Abs) are widely used for advanced melanoma, but information on the efficacy of anti-PD-1 Abs is limited in the Asian population. There remains an unmet need to improve the therapeutic effects of anti-PD-1 Ab-treatment, particularly in patients with melanoma who are refractory to anti-PD-1 Abs. The aim of this study was to evaluate anti-PD-1 Ab-treatment in combination with TM5614 (a plasminogen activator inhibitor-1 inhibitor) in patients with unresectable melanoma.MethodsThe TM5614-MM study was a multicentre, open-label, single-arm, phase II clinical trial to evaluate the efficacy and safety of nivolumab in combination with TM5614 in patients with advanced, unresectable malignant melanoma recruited at seven Japanese institutes between 13 September 2021 and 31 March 2023. Patients with metastatic or unresectable melanoma previously treated with anti-PD-1 Abs were enrolled. Nivolumab 480 mg was administered intravenously every 4 weeks for 8 weeks, while TM5614 was administered orally at a dose of 120 mg (0–4 weeks) and 180 mg once daily (5–8 weeks). The primary endpoint was the overall response rate after 8 weeks of concomitant use of TM5614.ResultsThirty-nine patients were enrolled, and 34 patients were included in the anti-PD-1 Ab-refractory cohort. The overall response rate at 8 weeks was 25.9% (95% confidence interval 12.9–44.9%, P = 0.027) in 27 patients who were anti-PD-1 Ab-refractory based on investigator assessment in the protocol per set cohort. Seven patients discontinued treatment owing to progressive disease or adverse events. Treatment-related grade 3 or higher adverse events occurred in 3 of 39 patients (7.7%) in the intention-to-treat cohort.ConclusionsTM5614 in combination with nivolumab is well tolerated and effective in anti-PD-1 Ab-refractory unresectable melanoma.

2024-05-01·Journal of Thoracic Disease

Treatment rationale and protocol design: an investigator-initiated phase II study of combination treatment of nivolumab and TM5614, a PAI-1 inhibitor for previously treated patients with non-small cell lung cancer

Article

作者: Tsubata, Yukari ; Fukutani, Miki ; Kozuki, Toshiyuki ; Shoda, Hiroyasu ; Tamura, Atsushi ; Yoshida, Takako ; Hirata, Taizo ; Orihashi, Yasushi ; Sakamoto, Tomohiro ; Masuda, Takeshi ; Tsuji-Takayama, Kazue ; Aoki, Gaku ; Ichihara, Eiki ; Akita, Tomoyuki ; Hattori, Noboru ; Fujihara, Hideki ; Amagase, Harunobu ; Miyata, Toshio ; Motonaga, Masanori

BackgroundThere is no established standard 3^rd line treatment for patients with advanced non-small cell lung cancer (NSCLC). Although cytotoxic chemotherapeutic agents that are not used as 1^st or 2^nd line treatment are administrated as 3^rd line treatment, their anti-tumor efficacy is insufficient. Anti-programmed death ligand-1 (PD-L1)/programmed death-1 (PD1) treatment is more effective and less toxic than chemotherapy in anti-PD-L1/PD-1 treatment-naïve patients with NSCLC. Therefore, anti-PD-L1/PD-1 therapy is considered an appropriate 3^rd line treatment. However, the anti-tumor efficacy is limited in patients previously treated with anti-PD-L1/PD-1 antibody. Today, new drugs are needed to increase the efficacy of anti-PD-L1/PD-1 antibodies.MethodsThis open-label, single-arm, investigator-initiated phase II study is designed to evaluate combination treatment of nivolumab and TM5614, a plasminogen activator inhibitor (PAI-1) inhibitor as 3^rd or more line treatment in NSCLC patients who underwent standard treatment. The primary endpoint is the objective response rate and the secondary endpoints are progression-free survival (PFS), overall survival (OS), duration of response (DOR) and safety. Recruitment began in September 2023 and is expected to continue for approximately three years.DiscussionCurrently, there is no standard 3^rd line treatment for advanced NSCLC, and we hope that the findings of this study will facilitate more effective treatments in this setting. Ethics and dissemination: the study protocol conformed to the ethical principles outlined in the Declaration of Helsinki. All patients will provide written informed consent prior to enrollment. Results will be published in a peer-reviewed publication.Trial RegistrationThis study is registered to Japan Registry of Clinical Trials with number: jRCT2061230039 (19/July/2023).

2024-02-01·FEBS Open Bio

A PAI‐1 antagonist ameliorates hypophosphatemia in the Hyp vitamin D‐resistant rickets model mouse

Article

作者: Qian, Cheng ; Asou, Yoshinori ; Miyata, Toshio ; Kikuchi, Katsushi ; Ito, Nobuaki ; Tsuji, Kunikazu ; Sato, Shingo ; Yoshii, Toshitaka

Congenital fibroblast growth factor 23 (FGF23)‐related hypophosphatemic rickets/osteomalacia is a rare bone metabolism disorder characterized by hypophosphatemia and caused by genetic abnormalities that result in excessive secretion of FGF23. Hyp mice are a model of X‐linked hypophosphatemia (XLH) caused by deletion of the PHEX gene and excessive production of FGF23. The purpose of this study was to investigate the potential of TM5614 as a therapeutic agent for the treatment of congenital FGF23‐related hypophosphatemic rickets and osteomalacia in humans by administering TM5614 to Hyp mice and examining its curative effect on hypophosphatemia. After a single oral administration of TM5614 10 mg·kg−1 to female Hyp mice starting at 17 weeks of age, the serum phosphate concentration increased with a peak at 6 h after administration. ELISA confirmed that TM5614 administration decreased the intact FGF23 concentration in the blood. Expression of 25‐hydroxyvitamin D‐1α‐hydroxylase protein encoded by Cyp27b1 mRNA in the kidney was suppressed in Hyp mice, and treatment with 10 mg·kg−1 of TM5614 normalized the expression of 25‐hydroxyvitamin D‐1α‐hydroxylase protein and Cyp27b1 mRNA in the kidneys of these mice. Our data indicate that oral administration of TM5614 ameliorates hypophosphatemia in Hyp mice, suggesting that TM5614 may be an effective treatment for congenital FGF23‐related hypophosphatemic rickets and osteomalacia.

100 项与 TM-5614 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
费城染色体阳性慢性粒细胞白血病	临床3期	日本	Renascience, Inc.	-
骨软化	临床2期	日本	Renascience, Inc.	2022-03-28
低磷血症佝偻病	临床2期	日本	Renascience, Inc.	2022-03-28
黑色素瘤	临床前	日本	Tohoku University	2020-08-26

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临床结果

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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


JPRN-jRCT2031190071 (Pubmed) 人工标引	临床2期	费城染色体阳性慢性粒细胞白血病	33	TM5614	遞憲觸鏇艱築艱窪顧襯(範淵廠獵襯窪廠廠衊窪) = 窪鹽鑰糧鬱積鹽窪獵夢窪選繭遞醖構鹹簾構鹽 (選觸襯糧觸窪選簾膚糧, 18.0 ~ 51.8)	积极	2022-09-23