A Single Arm Phase II Study to Evaluate Treatment With Gevokizumab in Patients With Stage II/III Colon Cancer Who Are ctDNA-positive After Curative Surgery and Adjuvant Chemotherapy

This study will look at the recurrence-free survival of microsatellite-stable (MSS) colon cancer in patients are ctDNA (circulating tumor DNA) positive and treated with gevokizumab.

Start Date24 Jun 2022

Sponsor / Collaborator

NSABP Foundation, Inc.

[+2]

NCT03798626 / Active, not recruitingPhase 1

Phase Ib Study of Gevokizumab in Combination With Standard of Care Anti-cancer Therapies in Patients With Metastatic Colorectal Cancer, Gastroesophageal Cancer and Renal Cell Carcinoma

This study will determine the pharmacodynamically-active dose of gevokizumab and the tolerable dose of gevokizumab in combination with the standard of care anti-cancer therapy in patients with metastatic colorectal cancer, metastatic gastroesophageal cancer and metastatic renal cell carcinoma, and the preliminary efficacy of gevokizumab in combination with the SOC anti-cancer therapy in subjects with mCRC and mGEC.

Start Date22 May 2019

Sponsor / Collaborator

Novartis Pharmaceuticals Corp.

CTR20150270 / SuspendedPhase 3

评估本品治疗已控制的非感染性中间、后或全葡萄膜炎的安全性和有效性的随机双盲安慰剂对照研究及亚组PK研究。

[Translation] A randomized, double-blind, placebo-controlled study and subgroup PK study to evaluate the safety and efficacy of this product in the treatment of controlled non-infectious intermediate, posterior or panuveitis.

这项研究的主要目的是证明Gevokizumab相对于安慰剂在当前用系统性治疗的控制期非感染性中间、后、或全葡萄膜炎患者中降低葡萄膜炎疾病复发风险的优效性。此外，还将对Gevokizumab的安全性进行评价。在中国大陆及高加索患者中，评价每4周接受一次（Q4W）30mg 或60mg剂量的Gevokizumab后，Gevokizumab的药代动力学。

[Translation]

The primary objective of this study is to demonstrate the superiority of Gevokizumab over placebo in reducing the risk of recurrence of uveitis disease in patients with non-infectious intermediate, posterior, or panuveitis who are currently treated with systemic therapy. In addition, the safety of Gevokizumab will be evaluated. The pharmacokinetics of Gevokizumab will be evaluated in patients from mainland China and Caucasians who receive Gevokizumab at a dose of 30mg or 60mg once every 4 weeks (Q4W).

Start Date24 Jul 2015

Sponsor / Collaborator

Les Laboratoires Servier SAS

[+2]

100 Clinical Results associated with Gevokizumab

100 Translational Medicine associated with Gevokizumab

100 Patents (Medical) associated with Gevokizumab

Literatures (Medical) associated with Gevokizumab

01 Oct 2024·Acta Biomaterialia

Glucose and pH dual-responsive hydrogels with antibacterial, reactive oxygen species scavenging, and angiogenesis properties for promoting the healing of infected diabetic foot ulcers

Article

Author: Yang, Jianmin ; Chen, Zelong ; Chen, Longhui ; Han, Jinzhi ; Zheng, Yunquan ; Shi, Xianai ; Li, Zhendong ; Yang, Shasha

The healing process of diabetic foot ulcers is challenging due to the presence of a complex and severe inflammatory microenvironment, characterized by hyperglycemia, low pH, susceptibility to infection, vascular dysfunction, and over-expression of reactive oxygen species (ROS), which can potentially lead to amputation or even mortality. Herein, a glucose and pH dual-responsive hydrogel was designed and prepared by crosslinking phenylboronic acid-grafted quaternary chitosan (QF, 4 wt%) with dopamine-grafted oxidized hyaluronic acid (OD, 5 wt%) through phenylboronation, schiff-base reaction, and other techniques. The multifunctional QO/@PV@AB7 hydrogel was prepared by incorporating pravastatin-loaded chitosan nanoparticles (CSNPs@PV, 2 mg/mL) and antimicrobial peptide AMP-AB7 loaded silica nanoparticles (SiO₂NPs@AB7, 0.5 mg/mL). The results demonstrate that the QO/@PV@AB7 hydrogel exhibits good responsiveness to acidic conditions and high glucose levels, while effectively scavenging various types of ROS. Moreover, it exerted protective effects against oxidative stress on cells, enhanced HUVECs viability, and promoted angiogenesis. Notably, the QO/@PV@AB7 hydrogel displayed potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli. Additionally, in an MRSA-infected rat model of diabetic foot wounds, administration of the QO/@PV@AB7 hydrogel led to increased secretion of pro-angiogenic factors such as vascular endothelial nitric oxide synthase (eNOS), vascular endothelial-generating factor (VEGF), and endothelial cell adhesion molecule (CD31). Furthermore, the hydrogel significantly reduced the levels of inflammatory factors such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while simultaneously increasing the levels of anti-inflammatory cytokines such as interleukin-10 (IL-10). The findings suggest that multifunctional hydrogels incorporating PV@CSNPs and SiO₂NPs@AB7 demonstrate promising potential as a therapeutic approach for the treatment of diabetic foot. STATEMENT OF SIGNIFICANCE: Here, a glucose and pH dual-responsive QO/@PV@AB7 hydrogel with antimicrobial and angiogenesis-promoting properties was developed for the treatment of infected wounds in diabetic feet. Our findings demonstrate that the proposed hydrogel exhibits good responsiveness, effectively scavenges various types of reactive oxygen species (DPPH, O^2-, -OH, and ABTS+), provides protection against oxidative stress, enhances HUVECs cell viability, and promotes angiogenesis. Notably, it also demonstrates potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) and E. coli. Additionally, in vivo experiments demonstrated that the hydrogel exhibited accelerated wound healing in MRSA-infected diabetic foot ulcers, with a reduction of four days compared to the control group.

01 Nov 2023·Applied microbiology and biotechnology

Rational design of Abhisin-like peptides enables generation of potent antimicrobial activity against pathogens.

Article

Author: Wu, Peifen ; Chen, Zhiying ; Yu, Fengfan ; Chen, Chi ; Yang, Jie ; Weng, Yanlin ; Han, Jinzhi ; Chen, Shunxian ; Ni, Li ; Lin, Yayi ; Li, Ruili ; Lü, Xucong

Infections caused by pathogens can be a significant challenge in wound healing, particularly when antimicrobial resistance is a factor. This can pose a serious threat to human health and well-being. In this scenario, it is imperative to explore novel antimicrobial agents to fight against multi-drug resistant (MDR) pathogenic bacteria. This study employed rational design strategies, including truncation, amino acid replacement, and heterozygosity, to obtain seven α-helical, cationic, and engineered peptides based on the original template of Abhisin. Among the analogs of Abhisin, AB7 displayed broad-spectrum and potent antimicrobial activity, superior targeting of membranes and DNA, and the ability to disrupt biofilms and anti-endotoxins in vitro. Additionally, we evaluated the anti-infection ability of AB7 using a murine skin wound model infected with methicillin-resistant Staphylococcus aureus (MRSA) and found that AB7 displayed negligible toxicity both in vitro and in vivo. Furthermore, AB7 exhibited desirable therapeutic efficacy by reducing bacterial burden and pro-inflammatory mediators, modulating cytokines, promoting wound healing, and enhancing angiogenesis. These results highlight the potential of AB7 as a promising candidate for a new antibiotic. KEY POINTS: • A α-helical, cationic, and engineered peptide AB7 was obtained based on Abhisin. • AB7 exhibited potent antimicrobial activity and multiple bactericidal actions. • AB7 effectively treated infected skin wounds in mice.

01 Aug 2023·Oncology letters

Efficacy and safety of envafolimab in the treatment of advanced dMMR/MSI‑H solid tumors: A single‑arm meta‑analysis.

Article

Author: Fan, Shaoqing ; Li, Baokun ; Wang, Guiying ; Gai, Chunyue

In November 2021, the National Medical Products Administration (China) approved the marketing of envafolimab injection for the treatment of advanced defective mismatch repair (dMMR)/high microsatellite instability (MSI-H) solid tumors. Envafolimab became the first domestic PD-L1 inhibitor approved in China and the first worldwide approved subcutaneously injectable PD-L1 inhibitor. To the best of our knowledge, there are no reports of systematic analyses regarding the use of envafolimab in the treatment of advanced dMMR/MSI-H solid tumors. The present study was a single-arm meta-analysis performed on data systematically searched and retrieved from literature published on PubMed, Web of Science, Cochrane Library, China National Knowledge Infra-structure and Wan Fang databases on 1 October 2022. Quality assessment using the 20 items developed by the Canadian Institute of Health Economics. Data heterogenicity was evaluated using the I² statistics. For datasets with I²>50%, the cumulative incidence and 95% CI for the outcomes of interests were calculated using the random effects model, whereas for I²<50% the fixed effects model was used. The current meta-analysis included four studies enrolling 181 patients with advanced dMMR/MSI-H solid tumors. The pooled objective remission rate was 29.53% (95% CI, 8.61-50.45%). The pooled disease control rate was 60.58% (95% CI, 31.79-89.38%). The pooled median progression-free survival was 4.89 months (95% CI, 1.86-7.93 months). The pooled overall survival (OS) rate was 73.38% (95% CI, 65.76-80.99%). The pooled 6-month and 12-month OS rates were 75.80% (95% CI, 57.02-94.58%) and 69.32% (95% CI, 51.92-86.72%), respectively. The combined data on the incidence of treatment-emergent adverse events (TEAEs) of any grade from all the studies was 77.19% (95% CI, 63.15-91.23%). Most of the adverse reactions were mild and the rate of 3/4 grade TEAE was 10.37% (95% CI, 6.14-14.60%). Gevokizumab was effective and safe in the treatment of patients with advanced dMMR/MSI-H solid tumors and its convenience could significantly improve patient compliance; therefore, the clinical application of envafolimab is promising.

News (Medical) associated with Gevokizumab

28 Aug 2023

·www.biospace.com

Novartis Abandons Xoma-Partnered Antibody for Pancreatic Cancer

Pictured: Novartis' office in Marburg, Germany/iStock, TBE Novartis is discontinuing the development of the anti-TGFβ antibody NIS793 and is returning it to Xoma Corporation, according to an SEC filing posted Friday. Following the discontinuation, Novartis will stop enrollment into all active clinical studies of NIS793 but will still collect data once these studies have concluded. After returning to Xoma, NIS793 will also remain an investigational compound. “Efficacy and safety have not been established. There is no guarantee that NIS793 will become commercially available,” Xoma wrote in its SEC filing. NIS793 is a fully human and potentially first-in-class monoclonal antibody that works by blocking the TGFβ cytokine, a protein involved in many cancer pathways including metastasis, vascular remodeling and immune evasion. The candidate had previously won the FDA’s Orphan Drug Designation for pancreatic cancer in July 2021. Novartis first gained access to NIS793 in October 2015, when it bought the asset from Xoma for $37 million upfront. The deal also involved up to $480 million in regulatory and commercial milestones. Before ending its development, Novartis was running a Phase III trial for NIS793 in pancreatic ductal adenocarcinoma, testing the candidate in combination with gemcitabine and nab-paclitaxel in the first-line setting. Novartis signed another licensing deal with Xoma in August 2017, gaining worldwide commercial rights to its anti-IL-1β antibody gevokizumab for $31 million. Prior to the deal, the candidate had already failed a Phase III trial for Behcet’s disease uveitis. Novartis is currently developing gevokizumab for the first-line treatment of colorectal cancer, with earlier planned submissions starting in 2026. The pancreatic cancer space has seen major developments lately. Last week, Exelixis stopped and unblinded its Phase III CABINET trial in advanced pancreatic and extra-pancreatic neuroendocrine tumors (NET) following “dramatic improvement” associated with its Cabometyx. There is currently no standard of care for NET patients who progress after initial treatment, representing a large unmet medical need. Cabometyx could potentially present these patients with a strong and effective treatment option. Exelixis will engage regulatory authorities using data from CABINET. In June 2023, Ipsen announced that the FDA had accepted its supplemental New Drug Application, seeking to expand Onivyde (irinotecan liposome injection) into the first-line setting for metastatic pancreatic ductal adenocarcinoma. Its application included data from the Phase III NAPOLI trial, which demonstrated significantly better overall and progression-free survival associated with Onivyde versus nab-paclitaxel and gemcitabine. The FDA’s verdict is due early next year. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3License out/inOrphan DrugClinical ResultNDA

25 Oct 2021

·www.biospace.com

Novartis Sees Glimmer of Hope in Phase III Lung Cancer Failure

lucarista/Shutterstock Novartis announced the CANOPY-1 Phase III trial of canakinumab failed to meet its primary endpoints when combined with Merck’s checkpoint inhibitor Keytruda (pembrolizumab) plus platinum-based doublet chemotherapy in non-small cell lung cancer (NSCLC). Specifically, the trial did not meet the primary endpoints of overall survival (OS) and progression-free survival (PFS) in patients receiving the combination therapy compared to the placebo cohort that received Keytruda plus platinum-based doublet chemotherapy in patients with previously untreated locally advanced or metastatic NSCLC. The study failed to meet statistical significance for those endpoints. Still, the company did say the study showed potentially clinically meaningful improvements in PFS and OS in pre-specified subgroups based on the baseline inflammatory biomarker, he-CRP, and other biomarker-defined subgroups. They believe this supports the continued study of the drug in lung cancer. “CANOPY-1 provides critical insights into the treatment of this devastating disease, and we will continue to analyze the data and conclusions, as well as their potential clinical implications,” said John Tsai, M.D., head of Global Drug Development and chief medical officer, Novartis. “While this trial did not confirm the benefit for all patients we hoped for, we are energized by the overall CANOPY-1 findings as they support our commitment to continue studying canakinumab in lung cancer. We share our gratitude and thanks to the CANOPY-1 study patients and clinical investigators for their partnership.” Canakinumab is a human monoclonal antibody that targets human interleukin-1beta (IL-1B) and neutralizes its activity. Data suggests this can inhibit Pro-Tumor Inflammation (PTI) from improving anti-tumor immune response and decreasing tumor cell proliferation, survival, invasiveness, and impairing angiogenesis. In March, the Phase III CANOPY-2 trial also failed to hit the primary endpoint of OS in second- or third-line treatment for patients whose cancer had progressed after previous chemotherapy or immunotherapy. This CANOPY-1 study seems to have similar responses. However, Novartis appears to believe it may still help treat cancer, particularly in earlier disease stages, such as when patients received it post-surgery (adjuvant) or neo-adjuvant (before surgery) in NSCLC patients. The Phase II CANOPY-N trial is evaluating canakinumab in the neoadjuvant setting. It tests the drug alone and in combination with Keytruda in patients with resectable NSCLC before their surgery. CANOPY-A is a Phase III trial evaluating canakinumab in the adjuvant setting after surgical resection and cisplatin-based chemotherapy. The drug was initially developed for atherosclerotic disease, but in 2017, the company found it came with a decreased risk of dying from lung cancer. Novartis and the industry are working to determine if drugs that affect the PTI pathway in NSCLC can be helpful. Novartis is also studying gevokizumab, an antibody against IL-1B, in a Phase I trial. Late last week, Novartis inked an initial deal with Pfizer and BioNTech to expand its fill-and-finish activities for the companies’ COVID-19 vaccine. Novartis will leverage its sterile manufacturing plants at the Novartis Technical Operations site in Ljubljana, Slovenia. It expects to fill at least 24 million doses in 2022.

AntibodyVaccineImmunotherapy

19 Jan 2009

·www.in-pharmatechnologist.com

XOMA cuts manufacturing jobs as demand dips

XOMA has dramatically cut back on its manufacturing staff as part of restructuring that will lay off 42 per cent of the company’s total employees. The move will affect 144 employees and has been taken in response to forecasts that the company’s manufacturing capacity will be underutilised in 2009. Having manufactured sufficient quantities of XOMA 052 for planned Phase II studies the company is cutting back and will cease large scale production. XOMA is retaining the potential to resume large scale manufacturing in the future but for now will just maintain its pilot production capacity. Steven Engle, chairman and CEO of XOMA, said: " We have made a difficult, but necessary, decision driven by extremely challenging market conditions. Although manufacturing was fully utilised in the fourth quarter, forecasted manufacturing demand in 2009 will not meet expectations . “ The reductions are focused on manufacturing and related areas and associated general and administrative support. Today's actions will bring operating expenses more in line with expected revenue ." XOMA will incur a $3m charge in the first quarter of 2009 as it pays for severance and other charges related to the restructuring. However, once this charge has been paid the company expects to realise annualised savings of $27m. The remaining 197 employees will continue to develop its anti-inflammatory antibody drug candidate XOMA 052 for the treatment of Type 2 diabetes. In addition XOMA will continue to work on antibody discovery and development in conjunction with its pharmaceutical partners and the US government.

Antibody

100 Deals associated with Gevokizumab

External Link

KEGG	Wiki	ATC	Drug Bank
D09911	Gevokizumab	-	DB12119

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pyoderma Gangrenosum	Phase 3	US	XOMA (US) LLC	01 Nov 2014
Pyoderma Gangrenosum	Phase 3	AU	XOMA (US) LLC	01 Nov 2014
Pyoderma Gangrenosum	Phase 3	CA	XOMA (US) LLC	01 Nov 2014
Ocular inflammation	Phase 3	US	XOMA (US) LLC	01 Mar 2014
Uveitis, Intermediate	Phase 3	US	Les Laboratoires Servier SAS	04 Feb 2013
Uveitis, Intermediate	Phase 3	AR	Les Laboratoires Servier SAS	04 Feb 2013
Uveitis, Intermediate	Phase 3	AM	Les Laboratoires Servier SAS	04 Feb 2013
Uveitis, Intermediate	Phase 3	AU	Les Laboratoires Servier SAS	04 Feb 2013
Uveitis, Intermediate	Phase 3	AT	Les Laboratoires Servier SAS	04 Feb 2013
Uveitis, Intermediate	Phase 3	BR	Les Laboratoires Servier SAS	04 Feb 2013

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01965145 (EYEGUARD B, Pubmed) Manual	Phase 3	Behcet's uveitis	83	gevokizumab	axbogbtkoy(qfvgsqpsvo) = Gevokizumab did not significantly affect the risk of occurrence of ocular exacerbations. However, data suggested that gevokizumab could preserve visual acuity, reduce the uveitis severity, decrease the emergence of macular edema, and have a corticosteroid sparing effect. Gevokizumab was well tolerated ivzzyivrpm (pvfrnhadcx )	Negative	01 Jan 2018
				Placebo

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