-
Categories
-
Pharmaceutical Intermediates
-
Active Pharmaceutical Ingredients
-
Food Additives
- Industrial Coatings
- Agrochemicals
- Dyes and Pigments
- Surfactant
- Flavors and Fragrances
- Chemical Reagents
- Catalyst and Auxiliary
- Natural Products
- Inorganic Chemistry
-
Organic Chemistry
-
Biochemical Engineering
- Analytical Chemistry
- Cosmetic Ingredient
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
▎The content team editor of WuXi AppTec recently, Leap Therapeutics announced that the potential "first-in-class" antibody therapy DKN-01 developed by the company is compatible with BeiGene's anti-PD-1 antibody tislelizumab ( tislelizumab), combined with chemotherapy, achieved positive preliminary results in the Phase 2a clinical trial DisTinGuish, a first-line treatment of patients with advanced gastric cancer and gastroesophageal junction (GEJ) cancer
.
Among patients who received a complete course of DKN-01 treatment, the objective response rate (ORR) reached 68.
2%, and the ORR of patients with tumors with high DKK1 expression reached 90%
.
DKN-01 is a potential "first-in-class" antibody targeting DKK1
.
DKK1 is highly expressed in a variety of tumors.
It can up-regulate the expression of VEGFR2 by activating the Akt signaling pathway, thereby promoting vascular proliferation and providing nutrients for tumor survival and proliferation
.
On the other hand, it enhances the immunosuppressive ability of myeloid-derived suppressor cells (MDSC) by regulating the Wnt signaling pathway
.
In a variety of cancer patients including gastric cancer and gastroesophageal junction cancer, the high expression of DKK1 is associated with shortened overall survival
.
Moreover, real-world data show that the high expression of DKK1 is related to the poor response of patients with gastric cancer/gastric junction cancer to various chemotherapy methods
.
▲High expression of DKK1 is related to shortening of overall survival (picture source: Leap Therapeutics official website) DKN-01 can reduce vascular proliferation by combining with DKK1, and up-regulate key cytokines such as IFNγ, IL-15 and IL-33 Level, promote the death of tumor cells
.
It can also reprogram MDSC cells by activating the Wnt signaling pathway and reduce their immunosuppressive activity
.
▲The mechanism of action of DKN-01 (picture source: Leap Therapeutics official website) In January 2020, BeiGene and Leap Therapeutics reached a research and development cooperation, and obtained DKN-01 clinical development and development in Asia (except Japan), Australia and New Zealand.
Exclusive option and licensing rights for promotion
.
In this study, a total of 25 patients with gastric cancer/gastroesophageal junction cancer received DKN-01, tislelizumab and chemotherapy as a first-line combination therapy
.
The tumors of these patients do not express the HER2 receptor
.
The results of the test showed that among all patients who received a complete DKN-01 treatment cycle, the ORR was 68.
2%.
Among them, the ORR of patients with high DKK1 expression was 90%, and the ORR of patients with low DKK1 expression was 56%
.
The complete data of the trial will be announced at the ESMO conference opening this week
.
▲Efficacy data of combination therapy in the first-line treatment of patients with gastric cancer/gastric junction cancer (picture source: Leap Therapeutics official website) Leap Therapeutics will also cooperate with BeiGene to test DKN- in patients with gastric cancer/GFJ cancer that highly express DKK1 01 Combined with tislelizumab, the efficacy and safety of second-line therapy
.
▲DKN-01's clinical development project (picture source: Leap Therapeutics company official website) Previously, DKN-01 was used in combination with the anti-PD-1 antibody Keytruda to treat gastric cancer/stomach that has not yet received PD-1/PD-L1 inhibitor treatment.
Positive preliminary clinical results are shown in patients with cancer of the esophagus junction
.
Among patients with high expression of DKK1, the combination of DKN-01 and Keytruda reached an ORR of 50%.
Compared with patients with low expression of DKK1, patients with high expression of DKK1 achieved longer progression-free survival and overall survival
.
▲Patients with high expression of DKK1 obtained longer progression-free survival after DKN-01 plus Keytruda treatment (picture source: Leap Therapeutics official website) "The preliminary data of the DisTinGuish study is very gratifying, it shows that DKN-01 and tislelizone Combination of anti- drug and chemotherapy has resulted in a high remission rate in first-line gastric cancer/gastric junction cancer patients
.
” said Dr.
Cynthia Sirard, chief medical officer of Leap Therapeutics, “Patients with high tumor expression of DKK1 have the highest remission rate, showing that this organism Markers play an important role in predicting the response to therapy
.
"Stomach cancer is the fifth most common cancer in the world and the third leading cause of cancer death
.
In China, gastric cancer is the second largest type of cancer after lung cancer
.
Its incidences and deaths accounted for 44% and 50% of the world's total
.
Chemotherapy has been the first choice of first-line treatment in the past few decades, but the effect is limited.
The 5-year survival period of patients with advanced or metastatic gastric cancer is only 5%
.
The treatment of gastric cancer has made a major breakthrough this year.
Bristol-Myers Squibb's PD-1 inhibitor Opdivo was approved by the US FDA, bringing first-line immune combination therapy to patients with gastric cancer/gastric esophageal junction cancer for the first time
.
We look forward to a new generation of combination therapies that can bring more effective treatment options to patients with gastric cancer/gastric esophageal junction cancer
.
Reference: [1] Leap Therapeutics to Present New Data from the DisTinGuish Study of DKN-01 Plus Tislelizumab at the ESMO 2021 Congress.
Retrieved September 14, 2021, from https://investors.
leaptx.
com/news-releases/news -release-details/leap-therapeutics-present-new-data-distinguish-study-dkn-01-plus[2] DKN-01 in combination with tislelizumab and chemotherapy as a first-line therapy in unselected patients with advanced gastroesophageal adenocarcinoma ( GEA): DisTinGuish trial.
Retrieved September 14, 2021, fromhttps://oncologypro.
esmo.
org/meeting-resources/esmo-congress-2021/dkn-01-in-combination-with-tislelizumab-and-chemotherapy-as- a-first-line-therapy-in-unselected-patients-with-advanced-gastroesophageal-adenocarcino[3] Leap Therapeutics Company Presentation.
Retrieved September 14, 2021, from https://fc949ce6-fa24-49e6-bbfd-6f920c9d5cba.
filesusr.
com/ugd/c343d0_0396914d915a43fab057cda07cd5f1ed.
pdf Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for the purpose of information exchange only.
The opinions expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes the views in the article
.
This article is not a treatment recommendation either
.
If you need guidance on the treatment plan, please go to a regular hospital for treatment
.
.
Among patients who received a complete course of DKN-01 treatment, the objective response rate (ORR) reached 68.
2%, and the ORR of patients with tumors with high DKK1 expression reached 90%
.
DKN-01 is a potential "first-in-class" antibody targeting DKK1
.
DKK1 is highly expressed in a variety of tumors.
It can up-regulate the expression of VEGFR2 by activating the Akt signaling pathway, thereby promoting vascular proliferation and providing nutrients for tumor survival and proliferation
.
On the other hand, it enhances the immunosuppressive ability of myeloid-derived suppressor cells (MDSC) by regulating the Wnt signaling pathway
.
In a variety of cancer patients including gastric cancer and gastroesophageal junction cancer, the high expression of DKK1 is associated with shortened overall survival
.
Moreover, real-world data show that the high expression of DKK1 is related to the poor response of patients with gastric cancer/gastric junction cancer to various chemotherapy methods
.
▲High expression of DKK1 is related to shortening of overall survival (picture source: Leap Therapeutics official website) DKN-01 can reduce vascular proliferation by combining with DKK1, and up-regulate key cytokines such as IFNγ, IL-15 and IL-33 Level, promote the death of tumor cells
.
It can also reprogram MDSC cells by activating the Wnt signaling pathway and reduce their immunosuppressive activity
.
▲The mechanism of action of DKN-01 (picture source: Leap Therapeutics official website) In January 2020, BeiGene and Leap Therapeutics reached a research and development cooperation, and obtained DKN-01 clinical development and development in Asia (except Japan), Australia and New Zealand.
Exclusive option and licensing rights for promotion
.
In this study, a total of 25 patients with gastric cancer/gastroesophageal junction cancer received DKN-01, tislelizumab and chemotherapy as a first-line combination therapy
.
The tumors of these patients do not express the HER2 receptor
.
The results of the test showed that among all patients who received a complete DKN-01 treatment cycle, the ORR was 68.
2%.
Among them, the ORR of patients with high DKK1 expression was 90%, and the ORR of patients with low DKK1 expression was 56%
.
The complete data of the trial will be announced at the ESMO conference opening this week
.
▲Efficacy data of combination therapy in the first-line treatment of patients with gastric cancer/gastric junction cancer (picture source: Leap Therapeutics official website) Leap Therapeutics will also cooperate with BeiGene to test DKN- in patients with gastric cancer/GFJ cancer that highly express DKK1 01 Combined with tislelizumab, the efficacy and safety of second-line therapy
.
▲DKN-01's clinical development project (picture source: Leap Therapeutics company official website) Previously, DKN-01 was used in combination with the anti-PD-1 antibody Keytruda to treat gastric cancer/stomach that has not yet received PD-1/PD-L1 inhibitor treatment.
Positive preliminary clinical results are shown in patients with cancer of the esophagus junction
.
Among patients with high expression of DKK1, the combination of DKN-01 and Keytruda reached an ORR of 50%.
Compared with patients with low expression of DKK1, patients with high expression of DKK1 achieved longer progression-free survival and overall survival
.
▲Patients with high expression of DKK1 obtained longer progression-free survival after DKN-01 plus Keytruda treatment (picture source: Leap Therapeutics official website) "The preliminary data of the DisTinGuish study is very gratifying, it shows that DKN-01 and tislelizone Combination of anti- drug and chemotherapy has resulted in a high remission rate in first-line gastric cancer/gastric junction cancer patients
.
” said Dr.
Cynthia Sirard, chief medical officer of Leap Therapeutics, “Patients with high tumor expression of DKK1 have the highest remission rate, showing that this organism Markers play an important role in predicting the response to therapy
.
"Stomach cancer is the fifth most common cancer in the world and the third leading cause of cancer death
.
In China, gastric cancer is the second largest type of cancer after lung cancer
.
Its incidences and deaths accounted for 44% and 50% of the world's total
.
Chemotherapy has been the first choice of first-line treatment in the past few decades, but the effect is limited.
The 5-year survival period of patients with advanced or metastatic gastric cancer is only 5%
.
The treatment of gastric cancer has made a major breakthrough this year.
Bristol-Myers Squibb's PD-1 inhibitor Opdivo was approved by the US FDA, bringing first-line immune combination therapy to patients with gastric cancer/gastric esophageal junction cancer for the first time
.
We look forward to a new generation of combination therapies that can bring more effective treatment options to patients with gastric cancer/gastric esophageal junction cancer
.
Reference: [1] Leap Therapeutics to Present New Data from the DisTinGuish Study of DKN-01 Plus Tislelizumab at the ESMO 2021 Congress.
Retrieved September 14, 2021, from https://investors.
leaptx.
com/news-releases/news -release-details/leap-therapeutics-present-new-data-distinguish-study-dkn-01-plus[2] DKN-01 in combination with tislelizumab and chemotherapy as a first-line therapy in unselected patients with advanced gastroesophageal adenocarcinoma ( GEA): DisTinGuish trial.
Retrieved September 14, 2021, fromhttps://oncologypro.
esmo.
org/meeting-resources/esmo-congress-2021/dkn-01-in-combination-with-tislelizumab-and-chemotherapy-as- a-first-line-therapy-in-unselected-patients-with-advanced-gastroesophageal-adenocarcino[3] Leap Therapeutics Company Presentation.
Retrieved September 14, 2021, from https://fc949ce6-fa24-49e6-bbfd-6f920c9d5cba.
filesusr.
com/ugd/c343d0_0396914d915a43fab057cda07cd5f1ed.
pdf Disclaimer: WuXi AppTec's content team focuses on introducing global biomedical health research progress
.
This article is for the purpose of information exchange only.
The opinions expressed in the article do not represent the position of WuXi AppTec, nor does it mean that WuXi AppTec supports or opposes the views in the article
.
This article is not a treatment recommendation either
.
If you need guidance on the treatment plan, please go to a regular hospital for treatment
.
