A Single Arm Study to Evaluate the Safety and Efficiency of Azacitidine (AZA) Combination With Venetoclax and ATRA in Patients With Newly Diagnosed Acute Myeloid Leukemia

This is a single arm study to evaluate the safety and efficiency of azacitidine (AZA) combination with venetoclax and ATRA in Patients With Newly diagnosed acute myeloid leukemia. Azacitidine, venetoclax and ATRA, may stop the growth of cancer cells, either by demethylation, by promoting cells differentiation or by killing the cells.

开始日期2022-10-31

申办/合作机构

苏州大学附属第一医院

NCT05388487

/ Recruiting临床1期

A Phase 1 Open-Label Dose-Escalation Study to Evaluate the Tolerability, DLT, Pharmacokinetics, and Preliminary Efficacy of HF1K16 in Patients With Refractory Solid Tumors

HF1K16 is an investigational pegylated liposome formulation of All-Trans Retinoic Acid (ATRA) for the induction of remission in patients with acute promyelocytic leukemia (APL) and for the treatment of solid tumors through targeting myeloid derived suppressor cells (MDSCs).

开始日期2022-02-16

申办/合作机构

杭州高田生物医药有限公司

[+1]

CTR20211361

/ Recruiting临床1期

评估注射用全反式维甲酸脂质体（HF1K16）作为单药治疗局部晚期或转移性实体瘤的耐受性，剂量限制性毒性、药代动力学特征和初步有效性的开放、多剂量、剂量递增Ⅰ期研究

主要目的：评估HF1K16单药治疗的耐受性，确定HF1K16单药治疗的剂量限制性毒性。确定HF1K16单药治疗的最大耐受剂量（MTD）（如有）。次要目的：评估HF1K16单药治疗的药代动力学特征。评估HF1K16单药治疗的初步抗肿瘤效果，以及HF1K16暴露量与受试者外周血淋巴细胞变化的关系。第五队列主要目的：评估HF1K16对复发或进展的脑胶质瘤的抗肿瘤效果。次要目的：受试者外周血淋巴细胞的变化。进一步评价HF1K16的安全性。

开始日期2022-02-07

申办/合作机构

杭州高田生物医药有限公司

100 项与全反式维甲酸脂质体相关的临床结果

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100 项与全反式维甲酸脂质体相关的转化医学

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100 项与全反式维甲酸脂质体相关的专利（医药）

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项与全反式维甲酸脂质体相关的文献（医药）

2015-01-01·BioMed Research International3区 · 生物学

Protective and Curative Effects of the Sea CucumberHolothuria atraExtract against DMBA-Induced Hepatorenal Diseases in Rats

3区 · 生物学

ArticleOA

作者: Amer, Sayed A. M. ; Mohamed, Ayman S. ; Fahmy, Sohair R. ; Dakrory, Ahmed I. ; Soliman, Amel M.

Oxidative stress is a common mechanism contributing to the initiation and progression of hepatic damage. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present study is to evaluate the efficacy ofHolothuria atraextract (HaE) as an antioxidant against 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hepatorenal dysfunction. Experimental animals were divided into two main groups: protective and curative. Each group was then divided into five subgroups pre- or posttreated either with distilled water (DMBA subgroups) or with HaE (200 mg/kg body weight) for seven and fourteen days. Single oral administration of DMBA (15 mg/kg body weight) to Wistar rats resulted in a significant increase in the serum liver enzymes and kidney function’s parameters. DMBA increased level of liver malondialdehyde (MDA), decreased levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) in the liver tissue, and induced liver histopathological alterations. Pre- or posttreatment with HaE orally for 14 days significantly reversed the hepatorenal alterations induced following DMBA administration. In conclusion, HaE exhibits good hepatoprotective, curative, and antioxidant potential against DMBA-induced hepatorenal dysfunction in rats that might be due to decreased free radical generation.

2014-02-01·Clinical Lymphoma Myeloma and Leukemia

Single-Agent Liposomal All-Trans-Retinoic Acid as Initial Therapy for Acute Promyelocytic Leukemia: 13-Year Follow-Up Data

Letter

作者: Kantarjian, Hagop ; Lopez-Berestein, Gabriel ; Pierce, Sherry ; Cortes, Jorge ; Estey, Elihu ; Ravandi, Farhad ; Jain, Preetesh

Clinical significance of all-trans retinoic acid (ATRA) in the initial therapy of acute promyelocytic leukemia (APL) is well established.[1],[2] Non-chemotherapeutic strategies have been sought to treat APL in order to avoid the adverse effects of chemotherapy.[3–6] Here, we report the 13 year follow up of a study of single agent liposomal-encapsulated ATRA in the frontline therapy of patients with APL[7]; the data were last updated in 2006.[8] Better pharmacokinetic data with liposomal ATRA [9] as compared with oral ATRA led to this study. The baseline characteristics of the 34 patients enrolled as well as the treatment protocol have been described previously. The complete remission (CR) rates were 79% (27/34) overall, and 92% (24/26) and 38% (3/8) among the low risk (with initial WBC counts <10,000) and in high risk (WBC ≥ 10,000) patients respectively (Table 1). Similar results were observed with respect to molecular response. The median time to hematological and molecular CR was 35 days (range, 24 – 64 days), and 123 days (range, 62 – 133 days), respectively. 27 patients achieved CR and one was lost to follow up. Among the 26 remaining patients, 24 had a molecular CR by qualitative PCR at 3 months. Eighteen patients maintained molecular remission after a median of 142.7 months (range, 18 – 172 months) after CR despite never having received any other antileukemic therapy. After a median follow up of 154.8 months (1.6–181.9 months), eleven patients have died. 5 of 11 deaths (45%) were early and 3 (30%) were due to cerebral hemorrhage. There were 8 relapses (6 alive, 2 dead), and a total of 17 events. The 13-year event-free survival (EFS), disease free survival (DFS) and overall survival (OS) were 46%, 69% and 65% respectively (Figure 1). The EFS and DFS were similar between low and high risk groups, while OS (not shown) was significantly longer in the low risk group (p=0.01). Since the study is limited by the small number of patients with disproportionate distribution among the low and high risk categories, the survival analyses among the risk categories may not be conclusive. Although, 8 patients who relapsed had low risk and none with high risk category relapsed, no definitive conclusions can be made due to the small number of patients. The eight relapses occurred after a median DFS of 11.9 months (range, 5–29 months) and six of the patients who relapsed were in molecular CR prior to relapse. Two relapsed patients underwent stem cell transplantation following salvage therapy with ATO, ATRA, ATO+ATRA, or ATO+ATRA+gemtuzumab ozogamicin, and both remain in remission at 11 and 12 years. Sixteen of the 18 patients who remain in molecular remission had low risk disease. None of the patients had any long term toxicities, in particular secondary myelodysplastic syndrome or AML, second malignancies or cardiotoxicity. These long term data suggest that liposomal ATRA is safe and has significant efficacy in patients with APL, even as monotherapy. We propose that liposomal ATRA is a potential lifesaving alternative to oral ATRA in situations where oral administration is difficult. Prospective studies (with larger cohorts of patients) combining liposomal ATRA with ATO in the frontline setting are warranted. Figure 1 Table -1 Distribution of patients among low and high risk categories

2010-07-01·Cancer Gene Therapy2区 · 医学

Enhanced growth inhibition of metastatic lung tumors by intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes in mice

2区 · 医学

Article

作者: M Hashida ; P Charoensit ; Y Higuchi ; F Yamashita ; S Kawakami

Interleukin 12 (IL-12) is a proinflammatory cytokine with antitumor activity. All-trans-retinoic acid (ATRA) exerts antitumor effects by regulating a variety of gene expressions, including tumor necrosis factor receptor 1 (TNFR1), increases the number of TNFR1 and potentiates TNF-alpha-induced apoptosis in cancer cells. In this study, ATRA-incorporated cationic liposome (ATRA-cationic liposome)/IL-12 plasmid DNA (pDNA) complexes were prepared to improve therapeutic efficacy of cationic liposome/IL-12 pDNA complexes in a mouse model of metastatic lung tumor after intravenous injection. IL-12 production in lungs by ATRA-cationic liposome/IL-12 pDNA complexes was comparable with that by cationic liposome/IL-12 pDNA complexes. The number of metastatic tumor cells (colon26/Luc) was quantitatively evaluated by measuring luciferase activity. ATRA-cationic liposome/IL-12 pDNA complexes reduced the number of colon26/Luc cells and tumor nodules in lungs. ATRA-cationic liposome/IL-12 pDNA complexes significantly prolonged the survival time of mice, whereas cationic liposome/IL-12 pDNA only slightly prolonged it. ATRA-cationic liposome/IL-12 pDNA complexes increased the TNFR1 mRNA upregulation and the number of apoptotic cells in the lung. Moreover, reduced serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were observed in mice treated with ATRA-cationic liposome/IL-12 pDNA complexes. These results suggest that intravenous injection of ATRA-cationic liposome/IL-12 pDNA complexes is an effective method for the treatment of lung metastasis in mice.

项与全反式维甲酸脂质体相关的新闻（医药）

2024-09-16

·Business Wire

Data from a Phase 1 Trial of HighField Biopharmaceuticals’ HF1K16 Show the New Immuno-Oncology Drug is Safe and Signals Efficacy in Treating Refractory Metastatic Cancers

HANGZHOU, China--( BUSINESS WIRE )-- HighField Biopharmaceuticals , a clinical stage company using lipid-based therapeutics to treat cancer, diabetes and other diseases, announced today its CEO and Scientific Founder Yuhong Xu, Ph.D, presented positive safety and efficacy findings from an ongoing Phase 1 clinical trial of HF1K16 (K16) in refractory metastatic cancer patients at the European Society of Medical Oncology (ESMO) Congress in Barcelona, Spain, September 13 – 17, 2024. K16 is an ATRA-encapsulated immune modulating liposome combining a lipid bilayer structure and all-trans retinoic acid (ATRA). It targets immature immune cells, called myeloid-derived suppressor cells (MDSCs), inducing them to become mature active immune cells, such as dendritic cells, which summon T cells to attack cancer. Presentation of the poster titled, “ A Phase 1 study of the Myeloid-derived suppressor cells modulator HF1K16 in refractory and metastatic cancer patients: preliminary efficacy and safety ,” was on Saturday, September 14 in the Investigational Immunotherapy session. “We are excited about the preliminary safety and efficacy data from our ongoing Phase 1 study,” said Dr. Xu. “ATRA is a highly active vitamin A metabolite commonly found in the body. Using Highfield’s liposome technology, we were able to inject a highly concentrated ATRA offering more than 10 times higher than normal exposure in a patient, triggering the therapeutic mechanism. These patients have very advanced, heavily prior treated tumors.” The Phase 1 dose escalation study ( NCT05388487 ) showed significant signals of desirable immune modulation and efficacy. The expansion cohort, currently recruiting, is focused on R/R glioma. As of Sept 1, 2024, 19 patients having Grade II, III and IV tumors have been enrolled. Among the 10 patients with Grade II and III gliomas, median overall survival (mOS) is 629 days. For the 9 patients with Grade IV or glioblastoma, the most aggressive brain tumors, mOS is 315 days. The next step will be to determine the indication that is most beneficial either as a single agent or in combination with other standard of care regimen in a Phase 2 study. About HighField Biopharmaceuticals Highfield is a clinical stage company focused on novel applications of liposome constructs directed to immuno-oncology and gene therapy for other diseases. The company also has a research and development center and a GMP-compliant production facility. HighField’s lead clinical development program is HFK16, a drug encapsulated immune modulating liposome. The company’s pipeline also includes an LipoADCplex TM platform comprised of drug encapsulated immunoliposomes for solid tumors as well as LNP therapeutics for gene delivery and gene therapy. For more information visit https://highfieldbio .

免疫疗法临床1期临床2期基因疗法临床结果

2024-05-28

·BioSpace

HighField Biopharmaceuticals ASCO 2024 Poster Presentation Shows HFK1, a Unique Immunoliposome May Improve Clinical Outcomes over Antibody Drug Conjugates

HFK1 is the company’s groundbreaking drug encapsulated immunoliposome for solid tumors with HER2 low expression HANGZHOU, China--(BUSINESS WIRE)-- HighField Biopharmaceuticals, a clinical stage company using lipid-based therapeutics to treat cancer, diabetes and other diseases, will present positive clinical and preclinical data of HFK1, a drug encapsulated immunoliposome for treatment of solid tumors, at the American Society of Clinical Oncology annual meeting May 31 – June 4, in Chicago, IL. The poster presentation describes preliminary findings from the company’s Phase 1a study of HFK1 for HER2 low expression cancers. The first patient dosed suffers from lung metastasis of a rare HER2 low cancer. The patient has been treated with HFK1 for more than five months with no dose-limiting toxicity and stable disease. The clinical and preclinical data, which will be presented by HighField CEO and Scientific Founder Yuhong Xu, Ph.D., also includes study results comparing HFK1 to other antibody drug conjugates (ADCs) and PEGylated liposomal doxorubicin (PLD). The findings demonstrate HFK1 improves significantly on the safety and efficacy of ADCs and PLD. In particular, HFK1 exceeded ADCs in expanding the drug therapeutic window and reducing tumor growth. “We look forward to sharing the encouraging data of our HFK1 studies at ASCO,” said Dr. Xu. “They confirm our confidence that our unique drug encapsulated immunoliposomes will offer a new alternative for targeting HER2 low cancers with lower off-target toxicities and wider therapeutic windows.” The poster, titled “The design, preclinical study and Phase 1 dose escalation of a HER2 targeted immunoliposome (HF-K1) for HER2 low solid tumor treatment,” will be presented Saturday, June 1, 2024 (9am -12pm CDT). HighField’s Phase 1 open-label clinical trial is enrolling patients who have advanced refractory solid tumors with HER2 low expression. The Phase 1a dose escalation portion will be followed by a Phase 1b dose expansion phase. Both the Phase 1a and 1b studies will assess the safety and preliminary efficacy of HFK1. For more information visit NCT05861895 on clinicaltrials.gov. HighField’s immunoliposomes represent a new generation of targeted chemotherapy drugs following the success of antibody drug conjugates (ADCs). Due to their unique features, HighField’s immunoliposomes may offer better safety with greater efficacy in treatment of a broad range of solid tumor types. About HighField Biopharmaceuticals HighField is a clinical stage company focused on novel applications of liposome constructs to disrupt existing immuno-oncology and other disease technologies. The company also has a research and development center and a GMP-compliant production facility. HighField’s lead clinical development program is HF1K16, a drug encapsulated immune modulating liposome containing all-trans retinoic acid targeting myeloid-derived suppressor cells for treatment of solid tumors. The company’s pipeline also includes drug encapsulated immunoliposomes for solid tumor cancers and lipid therapeutics for gene delivery and gene therapy. For more information visit . View source version on businesswire.com: Contacts Media Contact: Dan Eramian Opus Biotech Communications danieleramian@comcast.net 425-306-8716 Business Development Contact: Donald Wyatt HighField Biopharmaceuticals dwyatt@hf-biopharm.com 206-356-8196 Source: HighField Biopharmaceuticals View this news release online at:

临床1期免疫疗法ASCO会议抗体药物偶联物

2024-05-21

·BioSpace

HighField Biopharmaceuticals to Present Preclinical Data of HFG1, a Unique mRNA-based GLP-1R Agonist, for Treatment of Diabetes, at ADA’s 84th Scientific Sessions

Filing of a U.S. IND for HFG1 is scheduled for Q3/2024 HANGZHOU, China--(BUSINESS WIRE)-- HighField Biopharmaceuticals, a clinical stage company using lipid-based therapeutics to treat cancer, diabetes and other diseases, announced today that its abstract of preclinical data evaluating an mRNA-based GLP-1R agonist (HFG1) in diabetic monkeys has been accepted for a poster presentation at the American Diabetes Association (ADA) 84th Scientific Sessions June 21-24, 2024, in Orlando, FL. The abstract also will be published on the website of the ADA’s journal Diabetes. “We are very excited to introduce our unique lipid nanoparticle (LNP)-mRNA complex, HFG1, to the thousands of clinicians and researchers attending this year’s Scientific Sessions from around the world,” said HighField CEO and Scientific Founder Yuhong Xu, Ph.D. “The components of HFG1’s LNP complex were designed to provide consistent expression of a GLP-1R agonist for diabetes and weight loss. We believe HFG1 will require far fewer injections than existing GLP-1 products while providing steady-state agonist activity.” Abstract Title: Preliminary Study of Efficacy and Duration of an mRNA-Based GLP-1R Agonist in Diabetic Monkeys. (Poster presentation number 1860-LB in category 12-B Clinical Therapeutics-Incretin-Based Therapies). Presenter: Dr. Yuhong Xu, HighField CEO Presentation: Saturday, June 22, 2024, 12:30 pm – 1:30 pm EDT (The poster will be displayed Saturday, Sunday and Monday in the Poster Hall; and at a Networking Reception Friday evening.) About HighField Biopharmaceuticals HighField is a clinical stage company focused on novel applications of liposome constructs to disrupt existing immuno-oncology and other disease technologies. The company also has a research and development center and a GMP-compliant production facility. HighField’s lead clinical development program is HF1K16, a drug encapsulated immune modulating liposome containing all-trans retinoic acid targeting myeloid-derived suppressor cells for treatment of solid tumors. The company’s pipeline also includes drug encapsulated immunoliposomes for solid tumor cancers and lipid therapeutics for gene delivery and gene therapy. For more information visit . View source version on businesswire.com: Contacts Media Contact: Dan Eramian Opus Biotech Communications danieleramian@comcast.net 425-306-8716 Business Development Contact: Donald Wyatt HighField Biopharmaceuticals dwyatt@hf-biopharm.com 206-356-8196 Source: HighField Biopharmaceuticals View this news release online at:

免疫疗法临床研究

100 项与全反式维甲酸脂质体相关的药物交易

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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
脑癌	临床2期	中国	杭州高田生物医药有限公司	-
胶质瘤	临床1期	中国	杭州高田生物医药有限公司	2022-02-07

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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


NCT05388487 (ESMO2024) 人工标引	临床1期	肿瘤二线	17	HF1K16 45 mg/m2	(壓鑰遞鹽齋簾製膚遞顧) = 築衊鑰築餘蓋夢膚壓衊壓夢築蓋齋觸蓋觸範衊 (鹽觸鹹鹹窪鏇蓋糧壓醖 ) 更多	积极	2024-09-14
NCT05388487 (ASCO2024) 人工标引	临床1期	胶质瘤	12	HF1K16	(選築憲窪憲選壓繭築壓) = 簾觸構蓋製齋夢艱憲鬱獵範憲膚鹹繭廠構網鹽 (糧襯築憲範蓋衊齋憲醖 )	积极	2024-05-24
NCT05388487 (ASCO2024) 人工标引	临床1期	胶质瘤	12	HF1K16o	(選築憲窪憲選壓繭築壓) = 鬱襯糧齋憲夢顧夢淵選獵範憲膚鹹繭廠構網鹽 (糧襯築憲範蓋衊齋憲醖 )	积极	2024-05-24
NCT05388487 (Biospace) 人工标引	临床1期	实体瘤	14	HF1K16	(築壓構獵膚顧構膚獵膚) = 窪醖獵繭鹽糧窪衊衊範膚廠餘鹹糧醖獵獵構膚 (獵積鬱膚觸繭遞廠繭網 ) 更多	积极	2024-01-08
NCT05388487 (ASCO 12023 \| ASCO 22023) 人工标引	临床1期	肿瘤转移	11	HF1K16	(範糧顧膚鬱夢膚範網齋) = 顧壓壓憲簾糧簾廠範憲夢夢艱衊糧蓋鹽繭膚鏇 (糧齋膚廠觸範製鏇繭蓋 ) 更多	积极	2023-05-26