Track topics on Twitter Track topics that are important to you
For most advanced solid tumors, current therapy is inadequate at improving quality of life, slowing progression of disease, prolonging survival, and providing a cure. Hence, there is a continuous need for innovative, safer and more effective anti-cancer therapies. Our study is based on the dependence receptor paradigm and the associated therapeutic strategy. In preclinical models, preventing Netrin-1 interaction with its receptors is sufficient to trigger Netrin-1-expressing tumor cell death in vitro as well as tumor growth and metastasis inhibition in vivo. This indicates that a therapeutic approach based on Netrin-1/Netrin-1 receptors interaction inhibition is both feasible and promising. NP137 is a "first-in-class" humanized monoclonal antibody targeting the Netrin-1 ligand, a secreted protein recently described as a driver of tumor initiation and progression. NP137 demonstrated anti-tumor activity as a single agent in several pre-clinical models of cancer, including breast and lung cancer. Taken together, several studies strongly support the rational for preclinical development and clinical evaluation of a highly potent and selective anti-Netrin-1 antibody in cancer patients. The proposed study is an open label, multicenter, Phase I dose escalation study to assess the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and preliminary anti-tumor activity of NP137 administered every 2 weeks (Q2W) as single agent in patients with locally advanced or metastatic solid tumors. This trial will be the First in Human (FIH) study for NP137; there is no clinical experience with this antibody in the clinic. Dose escalation part will define the Maximum tolerated dose and the Recommended Phase II dose (MTD /RP2D) of NP137 and Expansion part will assess the PD and anti-tumor activity of NP137.
The dose escalation part (NP137 administered as a single agent by intravenous injection with up to 7 ascending dose levels) will be initiated with an accelerated dose titration with 1 patient per DL until the occurrence of a ≥ Grade 2 drug-related AE. Following the occurrence of such moderate toxicity, patients will be enrolled in a slower dose escalation design with at least 3 patients per DL using a Modified Continual Reassessment Method. Of note, in case no toxicity occurs up to the DL4, the classical 3+3 design will be initiated. In both parts, NP137 will continue to be administered as long as patient experience clinical benefit in the opinion of the investigator or until unacceptable toxicity or symptomatic deterioration attributed to disease progression as determined by the investigator after an integrated assessment of radiographic data and clinical status or withdrawal of consent or patient willingness to stop the treatment. In the expansion part, patients will be treated at the RP2D defined in Part 1.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Advanced Solid Tumor
Centre Léon Bérard
Not yet recruiting
Centre Leon Berard
Published on BioPortfolio: 2016-12-01T16:08:22-0500
This research study is studying an investigational combination of drugs as a possible treatment for advanced solid tumors: melanoma, ovarian, renal, or colorectal cancer. The drugs involv...
RATIONALE: ABT-510 and bevacizumab may stop the growth of solid tumors by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ...
This aim of study to assess the safety and tolerability of SHR7390 combined with SHR-1210 and to define Dose limiting toxicity（DLT）and the maximum tolerated dose (MTD) of SHR7390 in th...
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others inter...
This aim of study to assess the safety and tolerability of SHR7390 and to define the maximum tolerated dose (MTD) of SHR7390 in the patients with advanced solid tumors. To evaluate the ph...
Elenagen is a plasmid encoding p62/SQSTM1, the first DNA vaccine possessing two mutually complementing mechanisms of action: it elicits immune response against p62 and mitigates systemic chronic infla...
Pracinostat is a potent histone deacetylase inhibitor with antitumor activity in both solid tumor and acute myeloid leukemia (AML) cell lines. Pracinostat is reported to have modest clinical activity ...
A pathology-adaptive nanosystem, in which nest-like hosts are built based on nanofibers that are transformed from i.v. injected nanoparticles under acidic tumor microenvironment. The solid tumor is ar...
The MDM2 inhibitor MK-8242 is tolerable in patients with liposarcoma and other advanced solid tumors.
Solid pseudopapillary tumor of the pancreas (SPTP) is a rare neoplasm of low malignant potential with uncertain behavior, diagnosed mainly in young women.
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
A malignant cystic or semisolid tumor most often occurring in the ovary. Rarely, one is solid. This tumor may develop from a mucinous cystadenoma, or it may be malignant at the onset. The cysts are lined with tall columnar epithelial cells; in others, the epithelium consists of many layers of cells that have lost normal structure entirely. In the more undifferentiated tumors, one may see sheets and nests of tumor cells that have very little resemblance to the parent structure. (Hughes, Obstetric-Gynecologic Terminology, 1972, p184)
Mucocellular carcinoma of the ovary, usually metastatic from the gastrointestinal tract, characterized by areas of mucoid degeneration and the presence of signet-ring-like cells. It accounts for 30%-40% of metastatic cancers to the ovaries and possibly 1%-2% of all malignant ovarian tumors. The lesions may not be discovered until the primary disease is advanced, and most patients die of their disease within a year. In some cases, a primary tumor is not found. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1685)
A solid tumor consisting of a dense infiltration of MAST CELLS. It is generally benign.
An adenocarcinoma in which the tumor elements are arranged as finger-like processes or as a solid spherical nodule projecting from an epithelial surface.
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...