-
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
- Water Treatment Chemical
-
Pharmaceutical Intermediates
Promotion
ECHEMI Mall
Wholesale
Weekly Price
Exhibition
News
-
Trade Service
*Only for medical professionals to read and reference for 1 minute a day, to give you professional "talks" in the tumor circle! (If you need the original text of the document, you can add Xiaobian WeChat yxj_oncology to get it.
) Key points THE LANCET ONCOLOGY: Pyrotinib combined with capecitabine in the treatment of HER2-positive breast cancer with brain metastases Cancer Cell: MEK inhibitors may enhance immunity and chemotherapy New drug with synergistic effect: domestic FGFR inhibitor pemigatinib was approved for marketing in Hong Kong, China Approval of clinical 01THE LANCET ONCOLOGY: Pyrotinib combined with capecitabine in the treatment of HER2-positive breast cancer with brain metastases has a considerable effect.
HER2-positive metastatic breast cancer patients have a high risk of brain metastases and lack effective treatment options
.
Recently, a study investigating the activity and safety of pyrotinib combined with capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases was published in THE LANCET ONCOLOGY.
The treatment of HER2-positive breast cancer brain metastases has considerable clinical activity and safety
.
Screenshot of the official website The researchers conducted a multicenter, single-arm, two-cohort phase II trial in eight tertiary hospitals in China
.
Group A was naive HER2-positive brain metastases, and group B was patients with disease progression after radiotherapy.
They received pyrotinib 400 mg orally, once a day, and capecitabine 1000 mg/m2 orally, twice a day, for 14 days , followed by 7 days off every 3 weeks until disease progression or intolerable adverse events
.
The primary endpoint was investigator-confirmed intracranial objective response rate according to the Solid Tumor Response Evaluation Criteria (version 1.
1)
.
A total of 78 women were recruited between January 29, 2019, and July 10, 2020
.
The intracranial objective response rate was 74.
6% (95% CI: 61.
6–85.
0) in Group A and 42.
1% (95% CI: 20.
3–66.
5) in Group
B.
The most common sudden adverse reaction of grade 3 or higher was diarrhea (24% in arm A and 21% in cohort B)
.
Two (3%) patients in Arm A and three (16%) patients in Arm B had treatment-related serious adverse events
.
This is the first prospective study to show the activity and safety of pyrotinib in combination with capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naïve populations, and warrants a randomized controlled trial for further verification
.
02Cancer Cell: MEK inhibitors may enhance immune and chemotherapy synergy PD-1/PD-L1 inhibitor combination chemotherapy has become the standard treatment for patients with metastatic non-small cell lung cancer (mNSCLC), however, pemetrexed and cisplatin (PEM/CDDP) chemotherapy fails to synergize with immune checkpoint inhibitors (ICIs)
.
Recently, a study investigating MEK inhibitors to overcome chemoimmunotherapy resistance by inducing CXCL10 in cancer cells was published in Cancer Cell.
The results showed that the combination of MEK inhibitors and chemotherapy was synergistic with PD-L1 blockade
.
The researchers linked the failure of PEM/CDDP chemotherapy to synergize with ICIs in a lung tumor model and its inability to induce CXCL10 expression and CD8 T cell recruitment
.
Using drug screening, we found that combining a MEK inhibitor (MEKi) with PEM/CDDP triggers CXCL10 secretion and CD8 T cell recruitment in tumor cells, sensitizing them to ICIs
.
PEM/CDDP combined with MEKi promotes optic nerve protein (OPTN)-dependent mitophagy to produce CXCL10 in a mitochondrial DNA and TLR9-dependent manner
.
TLR9 or autophagy/mitochondrial inhibition abolished the antitumor efficacy of PEM/CDDP combined with MEKi/anti-PD-L1 therapy
.
Our findings underscore the role of TLR9 and OPTN-dependent mitophagy in enhancing the efficacy of chemoimmunotherapy
.
03New Drugs: Domestic FGFR Inhibitor Pemigatinib Approved for Listing in Hong Kong, China Following the approval of the U.
S.
Food and Drug Administration (FDA) in April 2020, Innovent announced on January 24 that Pemigatinib was approved by the Hong Kong Special Administrative Region Approved by the Government Department of Health (DH) for the treatment of adults with progressive disease, unresectable locally advanced or metastatic bile ducts with fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement after at least one prior systemic therapy cancer
.
Pemigatinib is a potent and selective oral inhibitor of FGFR subtypes 1/2/3
.
A phase II, open-label, single-arm, multicenter study of pemigatinib called FIGHT202 showed an objective response rate of 37.
0% (95%CI: 27.
94-46.
86) and was well tolerated, including hyperphosphatemia As the most common adverse reaction, the incidence rate was 58.
5%
.
04New drug: Phase III clinical trial of tislelizumab combined with chemotherapy for the first-line treatment of gastric cancer achieved positive results Positive results from Phase III clinical trial of RATIONALE 305 in first-line treatment of gastric or gastroesophageal junction cancer
.
In an interim analysis, tislelizumab in combination with chemotherapy met the primary endpoint of overall survival (OS) in patients with positive PD-L1 expression, requiring further follow-up to assess overall survival in the intent-to-treat patient population (ITT) benefit
.
The safety results of tislelizumab were consistent with those observed in previous trials, with no new safety warnings arising from the use of tislelizumab in combination with chemotherapy
.
05New Drugs: Domestic Oral Small Molecular PD-L1 Inhibitors Approved for Clinical On January 24, the official website of the Center for Drug Evaluation (CDE) of the State Drug Administration of China showed that Heyu Medicine is a new oral small molecule PD-L1 inhibitor The clinical trial application for ABSK043 capsule was accepted
.
A number of PD-1/PD-L1 antibody drugs have been approved for marketing in the world, but no small molecule drugs have been approved
.
ABSK043 has started a Phase I clinical trial in Australia for solid tumors
.
ABSK043 can specifically bind to PD-L1 and induce its endocytosis from the cell surface, effectively inhibiting the PD-1/PD-L1 interaction and restoring PD-L1-mediated inhibition of T cell activation
.
As a small molecule PD-L1 inhibitor, ABSK043 can overcome the disadvantages of high cost of monoclonal antibody, low bioavailability of oral absorption, long half-life and immunogenicity
.
Reference: [1] Meric-Bernstam F, et al.
Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study [published online ahead of print, 2021 Sep 22].
Cancer Discov.
2021;10.
1158/2159-8290.
CD-21-0697.
doi:10.
1158/2159-8290.
CD-21-0697 https://cancerdiscovery.
aacrjournals.
org/content/early/2022/ 01/19/2159-8290.
CD-21-0697[2]Limagne E, et al.
MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells[published online ahead of print,2022 Jan 17].
Cancer Cell.
2022; S1535-6108(21)00662-0.
doi:10.
1016/j.
ccell.
2021.
12.
009 https:// ://mp.
weixin.
qq.
com/s/8ot3LRqekpjIkMr3poD5rQ[4]https://mp.
weixin.
qq.
com/s/z8kAbwIOKdsS5h91FY4Q9Q[5]https://mp.
weixin.
qq.
com/s/f7ZEX8ynopEjoVkHQSKWgg
) Key points THE LANCET ONCOLOGY: Pyrotinib combined with capecitabine in the treatment of HER2-positive breast cancer with brain metastases Cancer Cell: MEK inhibitors may enhance immunity and chemotherapy New drug with synergistic effect: domestic FGFR inhibitor pemigatinib was approved for marketing in Hong Kong, China Approval of clinical 01THE LANCET ONCOLOGY: Pyrotinib combined with capecitabine in the treatment of HER2-positive breast cancer with brain metastases has a considerable effect.
HER2-positive metastatic breast cancer patients have a high risk of brain metastases and lack effective treatment options
.
Recently, a study investigating the activity and safety of pyrotinib combined with capecitabine in patients with HER2-positive metastatic breast cancer and brain metastases was published in THE LANCET ONCOLOGY.
The treatment of HER2-positive breast cancer brain metastases has considerable clinical activity and safety
.
Screenshot of the official website The researchers conducted a multicenter, single-arm, two-cohort phase II trial in eight tertiary hospitals in China
.
Group A was naive HER2-positive brain metastases, and group B was patients with disease progression after radiotherapy.
They received pyrotinib 400 mg orally, once a day, and capecitabine 1000 mg/m2 orally, twice a day, for 14 days , followed by 7 days off every 3 weeks until disease progression or intolerable adverse events
.
The primary endpoint was investigator-confirmed intracranial objective response rate according to the Solid Tumor Response Evaluation Criteria (version 1.
1)
.
A total of 78 women were recruited between January 29, 2019, and July 10, 2020
.
The intracranial objective response rate was 74.
6% (95% CI: 61.
6–85.
0) in Group A and 42.
1% (95% CI: 20.
3–66.
5) in Group
B.
The most common sudden adverse reaction of grade 3 or higher was diarrhea (24% in arm A and 21% in cohort B)
.
Two (3%) patients in Arm A and three (16%) patients in Arm B had treatment-related serious adverse events
.
This is the first prospective study to show the activity and safety of pyrotinib in combination with capecitabine in patients with HER2-positive breast cancer and brain metastases, especially in radiotherapy-naïve populations, and warrants a randomized controlled trial for further verification
.
02Cancer Cell: MEK inhibitors may enhance immune and chemotherapy synergy PD-1/PD-L1 inhibitor combination chemotherapy has become the standard treatment for patients with metastatic non-small cell lung cancer (mNSCLC), however, pemetrexed and cisplatin (PEM/CDDP) chemotherapy fails to synergize with immune checkpoint inhibitors (ICIs)
.
Recently, a study investigating MEK inhibitors to overcome chemoimmunotherapy resistance by inducing CXCL10 in cancer cells was published in Cancer Cell.
The results showed that the combination of MEK inhibitors and chemotherapy was synergistic with PD-L1 blockade
.
The researchers linked the failure of PEM/CDDP chemotherapy to synergize with ICIs in a lung tumor model and its inability to induce CXCL10 expression and CD8 T cell recruitment
.
Using drug screening, we found that combining a MEK inhibitor (MEKi) with PEM/CDDP triggers CXCL10 secretion and CD8 T cell recruitment in tumor cells, sensitizing them to ICIs
.
PEM/CDDP combined with MEKi promotes optic nerve protein (OPTN)-dependent mitophagy to produce CXCL10 in a mitochondrial DNA and TLR9-dependent manner
.
TLR9 or autophagy/mitochondrial inhibition abolished the antitumor efficacy of PEM/CDDP combined with MEKi/anti-PD-L1 therapy
.
Our findings underscore the role of TLR9 and OPTN-dependent mitophagy in enhancing the efficacy of chemoimmunotherapy
.
03New Drugs: Domestic FGFR Inhibitor Pemigatinib Approved for Listing in Hong Kong, China Following the approval of the U.
S.
Food and Drug Administration (FDA) in April 2020, Innovent announced on January 24 that Pemigatinib was approved by the Hong Kong Special Administrative Region Approved by the Government Department of Health (DH) for the treatment of adults with progressive disease, unresectable locally advanced or metastatic bile ducts with fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement after at least one prior systemic therapy cancer
.
Pemigatinib is a potent and selective oral inhibitor of FGFR subtypes 1/2/3
.
A phase II, open-label, single-arm, multicenter study of pemigatinib called FIGHT202 showed an objective response rate of 37.
0% (95%CI: 27.
94-46.
86) and was well tolerated, including hyperphosphatemia As the most common adverse reaction, the incidence rate was 58.
5%
.
04New drug: Phase III clinical trial of tislelizumab combined with chemotherapy for the first-line treatment of gastric cancer achieved positive results Positive results from Phase III clinical trial of RATIONALE 305 in first-line treatment of gastric or gastroesophageal junction cancer
.
In an interim analysis, tislelizumab in combination with chemotherapy met the primary endpoint of overall survival (OS) in patients with positive PD-L1 expression, requiring further follow-up to assess overall survival in the intent-to-treat patient population (ITT) benefit
.
The safety results of tislelizumab were consistent with those observed in previous trials, with no new safety warnings arising from the use of tislelizumab in combination with chemotherapy
.
05New Drugs: Domestic Oral Small Molecular PD-L1 Inhibitors Approved for Clinical On January 24, the official website of the Center for Drug Evaluation (CDE) of the State Drug Administration of China showed that Heyu Medicine is a new oral small molecule PD-L1 inhibitor The clinical trial application for ABSK043 capsule was accepted
.
A number of PD-1/PD-L1 antibody drugs have been approved for marketing in the world, but no small molecule drugs have been approved
.
ABSK043 has started a Phase I clinical trial in Australia for solid tumors
.
ABSK043 can specifically bind to PD-L1 and induce its endocytosis from the cell surface, effectively inhibiting the PD-1/PD-L1 interaction and restoring PD-L1-mediated inhibition of T cell activation
.
As a small molecule PD-L1 inhibitor, ABSK043 can overcome the disadvantages of high cost of monoclonal antibody, low bioavailability of oral absorption, long half-life and immunogenicity
.
Reference: [1] Meric-Bernstam F, et al.
Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study [published online ahead of print, 2021 Sep 22].
Cancer Discov.
2021;10.
1158/2159-8290.
CD-21-0697.
doi:10.
1158/2159-8290.
CD-21-0697 https://cancerdiscovery.
aacrjournals.
org/content/early/2022/ 01/19/2159-8290.
CD-21-0697[2]Limagne E, et al.
MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells[published online ahead of print,2022 Jan 17].
Cancer Cell.
2022; S1535-6108(21)00662-0.
doi:10.
1016/j.
ccell.
2021.
12.
009 https:// ://mp.
weixin.
qq.
com/s/8ot3LRqekpjIkMr3poD5rQ[4]https://mp.
weixin.
qq.
com/s/z8kAbwIOKdsS5h91FY4Q9Q[5]https://mp.
weixin.
qq.
com/s/f7ZEX8ynopEjoVkHQSKWgg
