A Phase II clinical study to evaluate the efficacy and safety of pleural perfusion of recombinant modified human tumor necrosis factor combined with sindrelimab plus chemotherapy in first-line treatment of driver negative non-squamous non-small cell lung cancer (NSCLC) with malignant pleural effusion

Start Date15 Nov 2023

Sponsor / Collaborator

Shandong First Medical University Affiliated Tumor Hospital (Shandong Cancer Research Institute Shandong Tumor Hospital)

CTR20233523 / Not yet recruitingPhase 3

注射用重组改构人肿瘤坏死因子（rmhTNF-NC，天恩福®）联合顺铂对比顺铂腔内灌注治疗恶性胸腹腔积液的有效性和安全性随机、双盲、平行对照的多中心III期临床试验

[Translation] A randomized, double-blind, parallel-controlled, multicenter phase III clinical trial on the efficacy and safety of recombinant human tumor necrosis factor for injection (rmhTNF-NC, Tianenfu®) combined with cisplatin versus intracavitary cisplatin perfusion in the treatment of malignant pleural and peritoneal effusions

主要有效性目的：以无穿刺生存期（Puncture-Free Survival，PuFS）和客观缓解率（ORR）作为主要疗效指标，评价rmhTNF-NC+顺铂相较于顺铂单药腔内灌注治疗恶性胸、腹腔积液的有效性。次要有效性目的：基于以下次要疗效指标，评价rmhTNF-NC+顺铂相较于顺铂单药腔内灌注治疗恶性胸、腹腔积液的有效性： 1)6个月生存率（6m-OS）； 2)疾病控制率（DCR）； 3)总生存期（OS）； 4)患者报告结局（PRO）：生活质量评分（QLQ评分）相对于基线的变化。安全性目的: 基于以下指标评估各治疗组的安全性： 1)不良事件的发生率和严重程度； 2)生命体征、体格检查、实验室检查（包括血常规、尿常规、血生化、凝血功能）以及心电图相对于基线的变化；特别关注不良事件（AESI）发生率。

[Translation]

Primary efficacy objective: Using puncture-free survival (PuFS) and objective response rate (ORR) as the primary efficacy indicators, evaluate the effectiveness of rmhTNF-NC + cisplatin compared with cisplatin monotherapy in the treatment of malignant pleural and peritoneal effusions. Secondary efficacy objective: Based on the following secondary efficacy indicators, evaluate the effectiveness of rmhTNF-NC + cisplatin compared with cisplatin monotherapy in the treatment of malignant pleural and peritoneal effusions: 1) 6-month survival rate (6m-OS); 2) disease control rate (DCR); 3) overall survival (OS); 4) patient-reported outcomes (PRO): changes in quality of life score (QLQ score) relative to baseline. Safety objective: The safety of each treatment group was evaluated based on the following indicators: 1) the incidence and severity of adverse events; 2) changes in vital signs, physical examination, laboratory tests (including blood routine, urine routine, blood biochemistry, coagulation function) and electrocardiogram relative to baseline; Special attention was paid to the incidence of adverse events (AESI).

Start Date-

Sponsor / Collaborator

Shanghai Wellcares Biopharmaceutical Co.,Ltd.

100 Clinical Results associated with Recombinant mutant human tumor necrosis factor

100 Translational Medicine associated with Recombinant mutant human tumor necrosis factor

100 Patents (Medical) associated with Recombinant mutant human tumor necrosis factor

115

Literatures (Medical) associated with Recombinant mutant human tumor necrosis factor

01 Dec 2020·BMC pulmonary medicineQ3 · MEDICINE

Thoracic perfusion of recombinant mutant human tumor necrosis factor (rmhTNF) can be considered as a good adjunct in the treatment of malignant pleural effusion caused by lung cancer

Q3 · MEDICINE

ArticleOA

Author: Zeng, Qingdi ; Fu, Tian ; Yao, Wei ; Lin, Yong ; Han, Liping

Abstract:

Background:

Tumor necrosis factor (TNF) has been investigated to be correlated with the occurrence and progression of lung cancer. This investigation was to assess the efficacy and safety of recombinant mutant human tumor necrosis factor (rmhTNF) for controlling malignant pleural effusion (MPE) through thoracic perfusion.

Methods:

Through searching from MEDLINE, Web of Science, EMBASE, Cochrance Library, OVID and China National Knowledge Infrastructure (CNKI), a total of 12 studies with 694 patients were included in this study. A series of meta-analysis methods were used to analyze the extracted data.

Results:

Thoracic perfusion of rmhTNF combined with cisplatin promoted the objective response rate (ORR) (P < 0.001; odds ratio = 4.49) and the quality of life (QOL) of patients with MPE (P < 0.001; odds ratio = 10.33), as compared with cisplatin alone. Although the participation of rmhTNF increased the incidence of fever (P < 0.001), it seemed to relieve the adverse reactions in the digestive tract (P = 0.017).

Conclusions:

Thoracic perfusion of rmhTNF contributes to the treatment of MPE and improves the QOL of MPE patients.

01 Jul 2015·European review for medical and pharmacological sciences

Role of Δ133p53 in Tumor Necrosis Factor-induced survival of p53 functions in MKN45 gastric cancer cell line.

Article

Author: Jiang, Q-Q ; Ji, W-S ; Gao, Z-X ; Guo, A ; Zhang, N ; Shang, Z-M ; Tang, J-D

OBJECTIVE:

To explore the role of Δ133p53 in the effect of recombinant mutant human Tumor Necrosis Factor (rmhTNF) on two gastric cancer cell lines.

MATERIALS AND METHODS:

MKN45 (with Δ133p53 expression) or SGC7901 (without Δ133p53 expression) cells were treated with rmhTNF of different concentrations only or combined with fluorouracil (5-FU), and the growth inhibition rate was detected by a cell counting kit, and apoptosis by flow cytometry. The mRNA of Δ133p53, p53, Gadd45α, MDM2, PTEN and Bax was measured by reverse transcription PCR (RT-PCR) or Nested PCR (nPCR).

RESULTS:

On Δ133p53-positive MKN-45 cells, the effect of rmhTNF was significant in growth inhibition test (t = -9.558, p < 0.01); also, the effect of 5-FU was improved by rmhTNF with remarkable time- and dose-effect (F = 82.742, p < 0.01; F = 128.583, p < 0.01). However, on Δ133p53-negative SGC-7901 cells, no growth inhibition was showed by rmhTNF only (t = -0.121, p > 0.05). In apoptosis test, the effect of rmhTNF was significant on MKN45 cells, and the effect of 5-FU was improved significantly by rmhTNF (F = 123.931, p < 0.05). In mRNA measurement, rmhTNF-induced up-regulation of p53 accompanied with down-regulation of Δ133p53, which correlated significantly to the change of p53 downstream molecules, including MDM2, PTEN, Gadd45α, and Bax.

CONCLUSIONS:

The results in these experiments suggested that Δ133p53 play a pivotal role in rmhTNF-induced survival of p53 functions in Δ133p53-positive MKN-45 cells.

01 Dec 2011·Particle and fibre toxicologyQ1 · MEDICINE

Shape matters: effects of silver nanospheres and wires on human alveolar epithelial cells

Q1 · MEDICINE

ArticleOA

Author: Albert Duschl ; Édgar Iván González ; Linda C Stoehr ; Eudald Casals ; Andreas Stampfl ; Victor Puntes ; Gertie J. Oostingh

Abstract:

Background:

In nanotoxicology, the exact role of particle shape, in relation to the composition, on the capacity to induce toxicity is largely unknown. We investigated the toxic and immunotoxic effects of silver wires (length: 1.5 - 25 μm; diameter 100 - 160 nm), spherical silver nanoparticles (30 nm) and silver microparticles (<45 μm) on alveolar epithelial cells (A549).

Methods:

Wires and nanoparticles were synthesized by wet-chemistry methods and extensively characterized. Cell viability and cytotoxicity were assessed and potential immunotoxic effects were investigated. To compare the effects on an activated and a resting immune system, cells were stimulated with rhTNF-α or left untreated. Changes in intracellular free calcium levels were determined using calcium imaging. Finally, ion release from the particles was assessed by ICP-MS and the effects of released ions on cell viability and cytotoxicity were tested.

Results:

No effects were observed for the spherical particles, whereas the silver wires significantly reduced cell viability and increased LDH release from A549 cells. Cytokine promoter induction and NF-κB activation decreased in a concentration dependent manner similar to the decrease seen in cell viability. In addition, a strong increase of intracellular calcium levels within minutes after addition of wires was observed. This toxicity was not due to free silver ions, since the samples with the highest ion release did not induce toxicity and ion release control experiments with cells treated with pre-incubated medium did not show any effects either.

Conclusions:

These data showed that silver wires strongly affect the alveolar epithelial cells, whereas spherical silver particles had no effect. This supports the hypothesis that shape is one of the important factors that determine particle toxicity.

100 Deals associated with Recombinant mutant human tumor necrosis factor

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R&D Status

Approved

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Indication	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	CN	Shanghai Wellcares Biopharmaceutical Co.,Ltd.	12 Jul 2004

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Malignant ascites	Phase 3	CN	Shanghai Wellcares Biopharmaceutical Co.,Ltd.	01 Jul 2024
Malignant Pleural Effusion	Phase 3	CN	Shanghai Wellcares Biopharmaceutical Co.,Ltd.	01 Jul 2024

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