This is a Phase I study designed to evaluate the safety and maximum tolerated dose (MTD) of SGT-94, a novel, tumor-targeted, systemic gene therapy agent for cancer. In addition, we will look for evidence of RB94 expression within tumor tissue after systemic administration of SGT-94.

开始日期2012-01-01

申办/合作机构

SynerGene Therapeutics, Inc.

100 项与 SGT-94 相关的临床结果

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100 项与 SGT-94 相关的转化医学

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100 项与 SGT-94 相关的专利（医药）

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项与 SGT-94 相关的文献（医药）

2019-09-17·Accounts of Chemical Research1区 · 化学

Survey of Clinical Translation of Cancer Nanomedicines—Lessons Learned from Successes and Failures

1区 · 化学

Review

作者: Schwendeman, Anna ; Liu, Min ; He, Hongliang ; Morin, Emily E. ; Liu, Lisha

In 1995, the year the first cancer nanomedicine, Doxil, was approved by the Food and Drug Administration (FDA), only 23 manuscripts appeared in a PubMed search for "nanoparticles for cancer" keywords. Now, over 25 000 manuscripts can be found using those same keywords, yet only 15 nanoparticle-based cancer nanomedicines are approved globally. Based on the clinicaltrials.gov database, a total of 75 cancer nanomedicines are under clinical investigation involving 190 clinical trials summarized here. In this Account, we focus on cancer nanomedicines that have been approved or reached clinical trials to understand this high attrition rate. We classify the various nanomedicines, summarize their clinical outcomes, and discuss possible reasons for product failures and discontinuation of product development efforts. Among ongoing and completed clinical trials, 91 (48 completed) are phase 1, 78 (59 completed) phase 2, and 21 (11 completed) phase 3. The success rate of phase 1 trials has been high-roughly 94%. Of those phase 1 trials with identified outcomes, 45 showed positive safety and efficacy results, with only one negative result (low efficacy) and two terminated due to adverse reactions. In some cases, findings from these trials have not only shown improved pharmacokinetics, but also avid drug accumulation within tumor tissues among active-targeting nanoparticles, including BIND-014, CALAA-01, and SGT-94. However, the success rate drops to ∼48% among completed phase 2 trials with identified outcomes (31 positive, 15 negative, and 4 terminated for toxicity or poor efficacy). A majority of failures in phase 2 trials were due to poor efficacy (15 of 19), rather than toxicity (4 of 19). Unfortunately, the success rate for phase 3 trials slumps to a mere ∼14%, with failures stemming from lack of efficacy. Although the chance of success for cancer nanomedicines starting from the proof-of-concept idea in the laboratory to valuable marketed product may seem daunting, we should not be discouraged. Despite low success rates, funding from the government, foundations, and research organizations are still strong-an estimated > $130 M spent by the National Institutes of Health (NIH) on R01s focused on nanomedicine in 2018 alone. In addition, the NIH created several special initiatives/programs, such as the National Cancer Institute (NCI) Alliance, to facilitate clinical translation of nanomedicines. Companies developing cancer nanomedicines raised diverse ranges of funds from venture capital, capital markets, and industry partnerships. In some cases, the development efforts resulted in regulatory approvals of cancer nanomedicines. In other cases, clinical failures and market pressure from improving standard of care products resulted in product terminations and business liquidation. Yet, recent approvals of nanomedicine products for orphan cancers and continuing development of nanoparticle based drugs for immune-oncology applications fuel continuing industrial and academic interest in cancer nanomedicines.

2016-08-01·Molecular Therapy1区 · 医学

A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers

1区 · 医学

Article

作者: Zhang, Xin-Qiao ; Leong-Wu, Cindy ; Shen, Yu ; Millikan, Randall E ; Pirollo, Kathleen F ; Leung, Chris ; Siefker-Radtke, Arlene ; Guo, Charles C ; Ling, Chi-Ming ; Sabir, Sharjeel ; Benedict, William F ; Chang, Esther H

Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy.

2008-04-01·Clinical Cancer Research1区 · 医学

Tumor-Targeting Nanocomplex Delivery of Novel Tumor Suppressor RB94 Chemosensitizes Bladder Carcinoma CellsIn vitroandIn vivo

1区 · 医学

Article

作者: Zhang, Xin-qiao ; Pirollo, Kathleen F. ; Zhou, Jain ; Chang, Esther H. ; Benedict, William F. ; Rait, Antonina ; Kim, Chang-Soo ; Zhou, Qi

AbstractPurpose: RB94, a truncated form of RB110, has enhanced tumor suppressor potency and activity against all tumor types tested to date including bladder carcinoma. However, efficient, systemic delivery of the gene encoding RB94 specifically to tumors, is an obstacle to clinical application as an anticancer therapeutic. We have developed a systemically given, nanosized liposome DNA delivery system that specifically targets primary and metastatic disease. The ability of RB94, delivered via this nanocomplex, to sensitize bladder carcinoma to chemotherapy in vitro and in vivo was assessed.Experimental Design: The nanocomplex is an RB94 plasmid encapsulated by a cationic liposome, the surface of which is decorated with a tumor-targeting moiety, either transferrin (Tf/Lip/RB94) or an antitransferrin receptor single-chain antibody fragment (TfRScFv/Lip/RB94). The ability of the complex to sensitize human bladder carcinoma HTB-9 cells to chemotherapeutics was assessed in vitro by XTT assay. In vivo tumor specificity and efficacy were tested in mice carrying HTB-9 tumors by PCR and tumor growth inhibition, respectively.Results: Transfection with Tf/Lip/RB94 significantly sensitized HTB-9 cells to chemotherapeutic agents in vitro. Tumor specificity of the complex was shown in an orthotopic bladder tumor model by immunohistochemistry and PCR. Moreover, in mice bearing subcutaneous HTB-9 tumors, the combination of systemically given Tf/Lip/RB94 or TfRScFv/Lip/RB94 plus gemcitabine resulted in significant (P < 0.0005) tumor growth inhibition/regression and induction of apoptosis.Conclusions: Use of our tumor-targeting nanocomplex to specifically deliver the potent tumor suppressor RB94 efficiently to tumors has potential as a more effective treatment modality for genitourinary and other cancers.

100 项与 SGT-94 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
肿瘤	临床1期	-	SynerGene Therapeutics, Inc.	-
实体瘤	临床1期	美国	-	-

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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


AACR2016	临床1期	肿瘤转移	-	SGT-RB94	鹹膚簾築憲夢膚製廠餘(餘顧構繭鬱衊淵構蓋網) = 27% 繭餘築蓋醖鹽襯積鹽繭 (獵鑰製艱蓋蓋鏇積鹽淵 ) 更多	积极	2016-07-15