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3rd line treatment for Gastric cancer
Global Phase III trials have been completed with Rivoceranib monotherapy for the third line gastric cancer treatment.
Rivoceranib is an oral target anticancer agent that selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), a major factor involved in angiogenesis in tumors.
VEGFR-2 inhibitor is the world's first synthetic drug to be approved for the treatment of gastric cancer.
In addition, we conducted clinical trials on thousands of patients in multiple countries including the US, Europe, Korea, and Japan to confirm their effectiveness in various cancers, including gastric cancer, colon cancer, hematological cancer, non-small cell cancer, esophageal cancer, and thyroid cancer.
Riboceranib has shown significant improvement in combination therapy and maintenance therapy with various drugs such as chemo and immunocancer drugs, and is undergoing various global clinical trials such as indication expansion studies and combination studies.
Smaller tumors can live without blood vessels by receiving oxygen by diffusion, but to grow more than 2mm in diameter, oxygen and nutrients must be supplied through the blood. Cancer cells secrete vascular endothelial growth factor (VEGF) for growth. When VEGF binds to receptors on the surface of vascular endothelial cells, it promotes angiogenesis, which supplies oxygen and nutrients. Metastasis can also occur through new blood vessels.
These representative angiogenesis promoters, VEGF, vary in VEGF-A, VEGF-B, VEGF-C, VEGF-D, and PIGF (placentl growth factor). Vascular endothelial cells contain vascular endothelial cell receptors (VEGFR) -1, 2, and 3 that accept vascular endothelial growth factors, and VEGFR-2 is involved in angiogenesis of cancer.
Rivoceranib is a tyrosine kinase inhibitor (TKI) small molecule that selectively inhibits VEGFR-2, which is involved in angiogenesis of cancer, and blocks the receptor signaling system of vascular endothelial cells. It inhibits the proliferation and migration of cells, preventing the formation of new blood vessels.
Two important processes of cells in our body are proliferation and apoptosis. However, unlike normal cells, cancer cells proliferate and die without control of the process of proliferation and death. According to the paper, Rivoceranib prohibits the proliferation and induces apoptosis of cancer cells.
The most important reason for the failure of chemotherapy is the multidrug resistance (MDR), which causes cancer cells to cross-resistant to several types of anticancer drugs. MDR is the most important cause of excessive production of proteins, such as glycoproteins (P-gp) or multidrug-resistant proteins, in the cell membranes of cancer cells. Anticancer drug resistant cancer cells reduce the efficacy of the anticancer drug by blocking the migration of the anticancer drug into the cancer cell or sending anticancer drug out of cells. It also changes the anticancer agent that enters the cell so that it cannot exert its anticancer effect. Rivoceranib improves drug efficacy by maintaining the concentration of intracellular anticancer drugs by inhibiting the activity of P-glycoprotein, which increases MDR or drug release.
As such, Rivoceranib may not only increase the effectiveness of other anticancer drugs, but also be effective in anticancer drug-resistant tumors, making it the best partner in combination therapy.
VEGF/VEGFR2 are known to be involved not only in the formation of blood vessels but also in the immunity of the tumor microenvironment. VEGF/VEGFR2 promotes the induction and proliferation of immunosuppressive Regulatory T cells (Tregs) and Myeloid Derived Suppressor Cells (MDSCs), while it inhibits the differentiation and activity of cytotoxic T lympnocytes (CTLs) and dendritic cells (DCs). In particular, the weakening of CTLs is known to be due to increased expression of immune barriers such as PD-1, CTLA-4, Tim-3, and Lag-3 via the VEGFR2 signaling pathway.
Riboceranib lowers the expression of PD-1, Tim-3, and Lag-3, which are immune barriers in CTLs, and stimulates the secretion of immune activators, IFN-r and IL-2, to activate immunity in the tumor microenvironment. This mechanism is expected to produce synergistic effects in combination therapy with immune gateway inhibitors.
The stomach, which is the largest digestive organ of our body, is located in the upper part of the abdomen, below the left ribs, and in the upper part of the abdomen.
The stomach is responsible for the storage and digestion of food.
Gastric cancer refers to all cancers of the stomach in principle, but it refers to gastric adenocarcinoma that occurs mainly in the glandular cells of the gastric mucosa. Gastric adenocarcinoma is classified into several types depending on the shape of the cancer cells observed under the microscope. In addition to gastric adenocarcinoma, lymphoma, which rarely develops in lymphoid tissues, gastrointestinal tumors in gastric stromal cells, sarcoma, a malignant tumor derived from non-epithelial cells, and neuroendocrine tumor that secrete hormones may occur.
The large intestine is a long tube-shaped digestive system that begins at the end of the small intestine and reaches the anus, which is about 150cm long. It is usually much shorter than the small intestine, which over 6m, but much wider. Cancer that occurs in this area is colorectal cancer.
The colon is divided into the appendix, the cecum, the colon, the rectum, and the anal canal, and the colon is divided into the ascending colon, the transverse colon, the descending colon, and the S-phase colon, among which malignant tumors of the cecum, colon and rectum are colon cancer. Most of the colorectal cancers are adenocarcinomas (adenocarcinoma), or cancers of the adenocarcinoma of the mucous membranes, and lymphomas, malignant carcinoids, and leiomyosarcomas may be primary.
The liver is the largest organ in our body, located just below the diaphragm and on the inside of the ribs below the right breast when viewed outward.
Liver cancer refers to primary malignant tumors that occur in the liver.
In general, cancer that has spread to the liver from other organs is often called liver cancer, but it is strictly referring to primary cancer.
There are various types of primary liver cancers, such as hepatocellular carcinoma (HCC), cholangiocarcinoma, hepatoblastoma, and hemangiosarcoma. Most of them are hepatocellular carcinoma and cholangiocarcinoma.
Adenoid cystic carcinoma (ACC) is a rare cancer that primarily affects salivary glands. It can also occur in the breast, skin, respiratory tract, and reproductive organs.
ACC is a malignant tumor with very high metastasis and a particularly severe onset around the nerves.
It shows slow growth rate, high recurrence rate (more than 40% after initial treatment) and aggressive tendency, low cure rate. In case of recurrence or metastasis after surgery or radiation treatment, chemotherapy is treated.
Chemotherapy is a combination treatment of Doxorubicin, Cisplatin, Cyclophosphamide, etc., but the effect is unclear. There is no standard chemotherapy.
* source: National Information Cancer Center
Indication | Mono/Combo | Phase 1 | Phase 2 | Phase 3 | NDA | ||||
GC (3rd/4th line) | Monotherapy |
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HCC (1st line) | Camrelizumab Combo |
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ACC (1st line) | Monotherapy |
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GC (2nd line) | Taxane Combo |
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CRC (3rd line) | TAS-102 Combo |
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Multiple Solid Tumors (Sarcoma) | Nivolumab Combo |
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Global Phase III trials have been completed with Rivoceranib monotherapy for the third line gastric cancer treatment.
Global Phase III trials are underway with a combination of Rivoceranib and Camrelizumab (PD-1 antibody therapeutics) from Chinese Hengrui medicine for the first line hepatocellular carcinoma.
Phase II clinical trials are underway in the US and Korea with Rivoceranib monotherapy for the 1st line Adenoid cystic carcinoma.
Phase I/II clinical trials are underway in Korea for a combination of Rivoceranib and Paclitaxel for the second line gastric cancer
Phase II clinical trials are in progress in the US and Korea for the combination of Rivoceranib and Taiho Pharmaceutical's Lonsurf in Japan for the third line colorectal cancer.
Clinical trials are in progress in the US for the combination of Rivoceranib and BMS's immunotherapy 'Opdivo' for sarcoma and various solid cancers.