Multi-arm, Phase II Clinical Study of Intraperitoneal Injection of Recombinant Human Tumor Necrosis Factor, Bevacizumab Monoclonal Antibody, and Serplulimab for the Treatment of Malignant Ascites Patients With Standard Therapy Failure

1. More than half of peritoneal metastases are from digestive tract. Peritoneal metastasis has poor prognosis, poor treatment response and limited means.
2. rmhTNF-NC or bevacizumab are effective in the treatment of malignant pleuroabdominal effusion.
3, There is increasing evidence that PD-1/PD-L1 inhibitors in combination with vascular endothelial growth factor receptor (VEGFR) inhibitors have a complementary mechanism of action: VEGF pathway inhibitors normalize blood vessels in tumors and promote immune cell maturation and infiltration, thus playing a synergistic role with ICIs. The strategy of systemic immunotherapy combined with antivascular therapy has been confirmed by several large phase III clinical trials such as IMbrave-150. Basic studies have confirmed that uncontrolled tumor vessels in peritoneal metastasis and malignant ascites microenvironment also play an important role in promoting disease progression. Therefore, this project intends to explore the treatment of malignant abdominal effusion by local intraperitoneal injection of bevacizumab and PD-1 on the basis of rmhTNF-NC

Start Date14 Dec 2023

Sponsor / Collaborator

Sun Yat-Sen University

CTR20233377 / RecruitingPhase 2

一项评价E10A联合帕博利珠单抗对照帕博利珠单抗治疗转移性或不可切除的复发性头颈鳞癌有效性和安全性的随机、开放、多中心II期临床研究

[Translation] A randomized, open-label, multicenter phase II clinical study to evaluate the efficacy and safety of E10A combined with pembrolizumab versus pembrolizumab in the treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma

主要目的：（1）与帕博利珠单抗比较，评估E10A与帕博利珠单抗联合使用的安全性和耐受性；（2）比较E10A联合帕博利珠单抗和帕博利珠单抗在CPS≥20的转移性或不可切除的复发性头颈鳞癌中的疗效。次要目的：（1）评价E10A联合帕博利珠单抗在头颈鳞癌患者中多次给药的药代动力学/药效动力学（PK/PD）特征。（2）评价E10A联合帕博利珠单抗在头颈鳞癌患者中多次给药的免疫原性特征。

[Translation]

Primary objectives: (1) To evaluate the safety and tolerability of E10A combined with pembrolizumab compared with pembrolizumab; (2) To compare the efficacy of E10A combined with pembrolizumab and pembrolizumab in metastatic or unresectable recurrent HNSCC with CPS ≥ 20. Secondary objectives: (1) To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of E10A combined with pembrolizumab after multiple dosing in patients with HNSCC. (2) To evaluate the immunogenicity characteristics of E10A combined with pembrolizumab after multiple dosing in patients with HNSCC.

Start Date04 Dec 2023

Sponsor / Collaborator

Guangzhou Doublle Bioproduct Co., Ltd.

CTR20150683 / CompletedPhase 3

评价重组人内皮抑素腺病毒注射液联合紫杉醇加顺铂对照紫杉醇加顺铂治疗头颈部鳞癌(非鼻咽癌)

[Translation] Evaluation of recombinant human endostatin adenovirus injection combined with paclitaxel plus cisplatin versus paclitaxel plus cisplatin in the treatment of head and neck squamous cell carcinoma (non-nasopharyngeal carcinoma)

主要目的:对比两组的无进展生存期（PFS）、对比两组的总生存期（OS）。次要目的:肿瘤客观缓解率；对比两组的安全性和耐受性；对比两组的生存质量；检测受试者局部用药前后及多次用药的Endostatin，VEGF-A 水平，了解 E10A 的表达及抗体对表达的影响。

[Translation]

Primary purpose: to compare the progression-free survival (PFS) and overall survival (OS) of the two groups. Secondary purpose: objective response rate of tumors; to compare the safety and tolerability of the two groups; to compare the quality of life of the two groups; to detect the levels of Endostatin and VEGF-A before and after local medication and multiple medications, and to understand the expression of E10A and the effect of antibodies on the expression.

Start Date08 Jul 2013

Sponsor / Collaborator

Guangzhou Doublle Bioproduct Co., Ltd.

100 Clinical Results associated with Recombinant human endostatin adenovirus(Sun Yat-Sen University)

100 Translational Medicine associated with Recombinant human endostatin adenovirus(Sun Yat-Sen University)

100 Patents (Medical) associated with Recombinant human endostatin adenovirus(Sun Yat-Sen University)

Literatures (Medical) associated with Recombinant human endostatin adenovirus(Sun Yat-Sen University)

01 Jan 2018·ClinicsQ4 · MEDICINE

Ethacrynic acid decreases expression of proinflammatory intestinal wall cytokines and ameliorates gastrointestinal stasis in murine postoperative ileus

Q4 · MEDICINE

ArticleOA

Author: Harada, Tomoyuki ; Fink, Mitchell ; Cruz, Ruy J

OBJECTIVESSeveral compounds characterized by an olefin linkage conjugated to a carbonyl group have anti-inflammatory properties. The diuretic ethacrynic acid (EA) is a compound of this type. Herein, we tested the hypothesis that ethacrynic acid can modulate the development of ileus after bowel manipulation.METHODSGroups (n=9) of male C57Bl/6 mice underwent surgical manipulation of the small intestine using a pair of cotton-tipped applicators (MAN). Control animals (CONT) did not undergo any surgical intervention or receive treatment. MAN mice were pre- and post-treated with four intraperitoneal doses of phosphate buffered saline (PBS), EA1 (1mg/kg per dose), or EA10 (10mg/kg per dose). Gastrointestinal transit of non-absorbable FITC-labeled dextran was assessed by gavaging the mice with the tracer 24h after operation and assessing FD70 concentration 120 min later in the bowel contents from the stomach, 10 equally long segments of small intestine, cecum, and two equally long segments of colon. The geometric center for the tracer was calculated for each animal. Expression of interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) transcripts in the ileal muscularis propria was assessed using semiquantitative reverse transcriptase-polymerase chain reaction.RESULTSIn control animals, the mean (±SE) geometric center for the transit marker was 9.89±0.47, whereas it was 4.59±0.59 for PBS-treated animals (p<0.05 vs CONT). The geometric center for pre- post treatment with low (1mg/kg) and high (10mg/kg) doses of ethacrynic acid were 7.23±0.97 and 5.15±0.57, respectively. Compared to PBS, treatment with ethacrynic acid (1mg/kg) significantly decreased manipulation-induced IL-6 and iNOS mRNA expression in the wall of the small bowel.CONCLUSIONSPre- and post-treatment with ethacrynic acid ameliorates ileus and modulates inflammation in the gut wall induced by bowel manipulation.

01 Jun 2014·Molecular TherapyQ1 · MEDICINE

Multicenter Randomized Phase 2 Clinical Trial of a Recombinant Human Endostatin Adenovirus in Patients with Advanced Head and Neck Carcinoma

Q1 · MEDICINE

Article

Author: Tiebang Kang ; Lixia Li ; George R Thomas ; Wen Tan ; Changchuan Pan ; Wen Ye ; Su Li ; Jiangxue Wu ; Li Zhang ; Wenlin Huang ; Ranyi Liu ; Qing Liu ; Wenqi Jiang ; Manli Huang ; Musheng Zeng ; Zhongzhen Guan ; Xiaofang Ying ; Wuguo Deng

A randomized, open-label, phase 2, multicenter clinical trial was conducted to evaluate the efficacy and safety of the addition of a recombinant human endostatin adenovirus (E10A) to cisplatin and paclitaxel in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma. Patients with locally advanced or metastatic head and neck squamous cell carcinoma or nasopharyngeal carcinoma not suitable for operation or radiotherapy were randomly assigned to receive E10A plus chemotherapy every 3 weeks for a maximum of six cycles or to receive chemotherapy only. One hundred and thirty-six eligible patients were randomly assigned. The addition of E10A did not significantly improve the objective response rate (29.9 versus 39.7%, P = 0.154). However, patients who received endostatin had longer progression-free survival (7.03 versus 3.60 months, P = 0.006; hazard ratio: 0.55). The combination of E10A with chemotherapy benefited prior chemotherapy-treated patients and those who received three to four treatment cycles (6.50 versus 3.43 months, P = 0.003; 8.27 versus 4.27 months, P = 0.018; respectively). The overall disease control rate significantly increased from 80.6% in the control group to 92.6% in the test group (P = 0.034). Except for fever, no adverse events were associated with the E10A treatment. In summary, E10A plus chemotherapy is a safe and effective therapeutic approach in patients with advanced head and neck squamous cell carcinoma or nasopharyngeal carcinoma.

01 May 2012·International Journal of PharmaceuticsQ2 · MEDICINE

Investigation on formulation and preparation of adenovirus encoding human endostatin lyophilized powders

Q2 · MEDICINE

Article

Author: Dongwei Guo ; Shuangning Chen ; Shengrong Guo ; Xiaofen Xu ; Yuanyuan Shen ; Baisong Guo ; Jieying Liu ; Wenlin Huang

A recombinant adenovirus encoding human endostatin gene, E10A, has finished phase II trials for head and neck cancer. However, the rigid storage temperature (-80°C) and the toxicity of glycerol in the E10A liquid preparation limited its clinical application. In this study, lyophilization was applied to develop a stable E10A lyophilized powder without glycerol that is able to maintain biological activity at 4°C and suitable for intravenous administration. The E10A lyophilized formulations composed of nontoxic and already clinically used excipients were characterized in terms of the pH change during freezing, the eutectic melting temperature (T(eu)) and the collapse temperature (T(c)). Freeze thawing tests were carried out to examine the protective effect of various excipients during freezing. Mannitol and its combinations with sucrose or inulin showed effective protection of E10A. The E10A lyophilized powders were analyzed by particle size measurement, residual humidity quantification, infectivity assay and gene expression level. An optimized formulation (formulation I1) yielded a good recovery of 76% of the starting infectivity after lyophilization and 89% of the original infectivity after storage at 4°C for 180 days. Also the gene expression capability of E10A in formulation I1 was maintained after lyophilization. In addition, it was found that the matrix of amorphous excipients, mannitol combinations with sucrose or inulin, was indispensible in protecting E10A against the stress of freezing and dehydration. Hereby, the E10A lyophilized powder with eliminated glycerol toxicity and improved stability could enhance the applicability of E10A for cancer gene therapy through intravenous administration.

100 Deals associated with Recombinant human endostatin adenovirus(Sun Yat-Sen University)

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Malignant ascites	Phase 2	CN	Sun Yat-Sen University	14 Dec 2023
Nasopharyngeal Carcinoma	Preclinical	CN	Guangzhou Doublle Bioproduct Co., Ltd.	08 Jul 2013
Squamous Cell Carcinoma of Head and Neck	Preclinical	CN	Guangzhou Doublle Bioproduct Co., Ltd.	08 Jul 2013

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Phase II trial (AHNS2014)	Phase 2	Head and neck cancer metastatic	140	E10A/chemotherapy	(ugnpefrosj) = blcmllaqlp uxbthzfzib (hnzeeiyybx ) View more	Positive	29 Jul 2014
				Chemotherapy	(ugnpefrosj) = ttydbrfxfs uxbthzfzib (hnzeeiyybx ) View more
Phase II Clinical Trial of Recombinant Human Endostatin Adenovirus (E10A) (ASGCT2012)	Phase 2	Head and Neck Neoplasms VEGF-induced tumor angiogenesis	140	E10A + Cisplatin + Paclitaxel	(qzaheinffk) = grade 1 or 2, 60.0% vs. 59.4%; grade 3 or 4, 7.1% vs. 5.8% cglvmbxuyw (xbmryiiqzc ) View more	Positive	01 May 2012
				Cisplatin + Paclitaxel

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

Recombinant human endostatin adenovirus(Sun Yat-Sen University)

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation