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*Only for medical professionals to read for reference, 1 minute a day, to give you professional "talking information" in the tumor circle! (If you need the original text of the literature, you can add the editor WeChat yxj_oncology to obtain) Key points CCR: PAM50-based chemical endocrine score can predict the efficacy and prognosis of HR+/HER2+ breast cancer neoadjuvant therapy CCR: Wee1 inhibitor Adavosertib once a day for advanced entities Tumor safe and effective new drug: Nivolumab combined with chemotherapy was approved by the FDA for the first-line treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma.
New drug: China’s first self-developed ADC drug is expected to be approved for gastric cancer 01CCR: PAM50-based chemical endocrine score can predict the efficacy and prognosis of neoadjuvant treatment for HR+/HER2+ breast cancer.
On April 16, Clinical Cancer Research reported a PAM50-based chemical endocrine score (CES) for hormone receptor positive/ Independent validation analysis of neoadjuvant anti-HER2 combination therapy for HER2-positive (HR+/HER2+) breast cancer showed that CES can effectively predict the chemoendocrine sensitivity and prognosis of HER2+/HR+ breast cancer.
The article release screenshots based on PAM50 CES can predict the chemoendocrine sensitivity of HR+/HER2- breast cancer.
However, it has not been verified whether CES based on PAM50 is a biomarker for predicting the efficacy and prognosis of HR+/HER2+ breast cancer.
This analysis aims to assess the association between CES and HR+/HER2+ breast cancer efficacy and survival.
Include 7 studies on HER2 targeted therapy combined with endocrine therapy (ET) or chemotherapy (CTX) in the treatment of HR+/HER2+ breast cancer patients, and obtain intrinsic subtypes and clinicopathological data from them.
Use CES as a continuous variable—from low to high scores [CES-C (chemically sensitive), CES-U (uncertain), and CES-E (endocrine sensitive)]; first analyze each data set separately, and then Analyze the combined data set.
Multivariate analysis was used to evaluate the association between CES and pathological complete response (pCR) and disease-free survival (DFS).
The results showed that a total of 457 patients were enrolled (112 patients received HER2 targeted therapy + ET and 345 patients received HER2 targeted therapy + CTX).
In the combined cohort, it was found that the proportions of CES-C, CES-U, and CES-E patients were 60%, 23%, and 17%, respectively.
High CES (ie, CES-E) is associated with a lower probability of obtaining pCR, but not with clinical features, treatment, intrinsic subtypes, and research (adjusted OR=0.
42; P=0.
016).
DFS analysis included 295 patients with a median follow-up of 66 months.
High CES was associated with better DFS (adjusted HR=0.
174; P=0.
003), but not with pCR, clinical features, and intrinsic subtypes.
In patients with residual disease, the adjusted DFS HR of CES was 0.
160 (P=0.
012).
The researchers said that for HR+/HER2+ breast cancer, CES can be used to predict chemical endocrine sensitivity, and can provide prognostic predictions beyond intrinsic subtypes and clinicopathological features.
02CCR: Wee1 inhibitor Adavosertib once a day is safe and effective in the treatment of advanced solid tumors.
On April 16, a phase I trial reported by Clinical Cancer Research showed that the Wee1 inhibitor Adavosertib (AZD1775) is safe to treat advanced solid tumors once a day.
,effective.
Article release screenshot Adavosertib can induce cell death.
Previous studies evaluating Adavosertib twice a day for the treatment of patients with advanced solid tumors determined the phase II recommended dose (RPh2D).
This study aims to evaluate the results of Adavosertib once daily.
Using a 3+3 dose escalation design, Adavosertib was administered once a day on Days 1-5 and Days 8-12 of a 21-day cycle.
Molecular biomarkers for Wee1 activity were evaluated in paired tumor biopsies, including Cdk1/2 (pY15-Cdk) phosphorylated at position 15 tyrosine.
Use the remaining tumor tissue to perform whole-exome sequencing and RNA sequencing to identify potential predictive biomarkers.
The results showed that among the 42 patients included, the most common adverse reactions were gastrointestinal and hematological toxicity; dose-limiting toxicity was grade 4 hematological toxicity and grade 3 fatigue.
The RPh2D of Adavosertib once a day is 300 mg.
6 patients (14%) were confirmed to have partial remission (PR): 4 cases of ovarian cancer and 2 cases of endometrial cancer.
The plasma exposure level of Adavosertib once daily is similar to that of twice daily administration.
On the 8th day of the first treatment cycle (before administration), 4 out of 8 patients had tumor pY15-Cdk levels higher than baseline, suggesting that there was a rebound in the therapeutic effect during the administration interruption on days 5-8.
One patient with rapid progression had WEE1 mutation and potential compensatory PKMYT1 overexpression.
Both of the 2 treatment responders had baseline CCNE1 overexpression, one of them had CCNE1 amplification, and none of the 3 non-responders had baseline CCNE1 overexpression.
The researchers said that the study determined the RPh2D of Adavosertib once a day and observed its activity in patients with ovarian cancer or endometrial cancer (including 2 patients with baseline CCNE1 mRNA overexpression).
Future studies will determine whether CCNE1 overexpression is a predictive biomarker of Adavosertib's efficacy.
03 New drug: Nivolumab combined with chemotherapy was approved by the FDA for the first-line treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma.
On April 17, the US Food and Drug Administration (FDA) announced the approval of PD-1 inhibition Nivolumab is used in combination with chemotherapy as a first-line therapy for advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma.
The press release stated that this is the first first-line immunotherapy approved by the FDA for the treatment of gastric cancer.
The approval is based on the results of a randomized, open-label Phase III clinical trial of CheckMate-649.
A total of 1581 untreated patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma were enrolled.
The results of the trial showed that the combination therapy of nivolumab and chemotherapy significantly improved the overall survival (OS) of patients.
The median OS was 13.
8 months in the nivolumab combination therapy group and 11.
6 months in the chemotherapy group.
Among patients whose tumors express PD-L1 (CPS>5), the nivolumab combined treatment group has a better effect, with a median OS of 14.
4 months and 11.
1 months in the chemotherapy group.
The nivolumab combination therapy group reduced the risk of death by 29% (HR=0.
71, 98.
4%CI 0.
59-0.
86, p<0.
0001).
In China, nivolumab has been approved by the National Medical Products Administration (NMPA) of China in March 2020 for the treatment of advanced or recurrent stomachs or stomachs that have received two or more systemic treatments in the past.
Patients with adenocarcinoma of the esophageal junction.
The main results of the Chinese subgroup of CheckMate-649 show that in the Chinese population, compared with chemotherapy alone, the first-line treatment of unresectable advanced or metastatic gastric cancer and gastroesophageal junction cancer with nivolumab combined with chemotherapy has achieved clinical Significant overall survival and progression-free survival (PFS) benefits.
The analysis results of the Chinese subgroup are consistent with the results of the global population as a whole.
04 New drug: China's first self-developed ADC new drug is expected to be approved for gastric cancer treatment.
On April 19, Rongchang Bio announced: "China's first self-developed antibody-conjugated drug (ADC), a new drug for vedixituzumab, has been approved countdown , Will usher in a new era of targeted tumor therapy".
According to the results of the priority review and publicity of the Center for Drug Evaluation (CDE) of the National Food and Drug Administration of China, the drug is intended to be used to treat HER2 overexpression locally advanced or metastatic gastric cancer (including gastroesophageal cancer) that has received at least 2 system chemotherapy after recurrence/metastasis The marketing application of junction cancer) has been included in the priority review, which means that the drug is about to be approved for gastric cancer.
Screenshot of the CDE official website.
Disitamab vedotin (RC48) is the first anti-HER2 ADC drug in my country to enter clinical research.
It is mainly used for the treatment of advanced or metastatic gastric cancer (GC) and urothelial cancer with HER2 expression.
(UC) and potential treatment of HER2 expression (including low expression) breast cancer patients.
Vidicizumab has been approved by the U.
S.
Food and Drug Administration (FDA) as an orphan drug.
The C008 study of the Phase II clinical trial of Vidicuzumab was conducted by Professor Lin Lin of Peking University Cancer Hospital as the main investigator.
It is a single-arm, single-arm, safety-related study aimed at the effectiveness and safety of HER2 overexpression in patients with locally advanced or metastatic gastric cancer.
The open, multi-center Phase II clinical study is also China's first single-group open clinical study for the third-line treatment of the ADC drug for HER2 overexpressing gastric cancer.
The results of the study showed that the objective response rate (ORR) of the drug in third-line and above HER2 overexpression locally advanced or metastatic gastric cancer reached 23.
6%, the median PFS was 4.
1 months, and the median OS was 7.
6 months.
The patient's survival status Almost as effective as second-line treatment.
Moreover, the study included patients with low HER2 expression, further expanding the target patient population.
In addition, studies have confirmed that it can benefit patients with HER2-expressing breast cancer and biliary tract cancer, as well as some other HER2-expressing solid tumor patients after the failure of conventional treatment.
In the future, it is hoped that the first Chinese self-developed ADC drug Vidicitor Monoclonal antibodies can play a role in the treatment of multiple tumors. References: [1] Tomás Pascual, Aranzazu Fernandez-Martinez, Maki Tanioka, et al.
Independent Validation of the PAM50-Based Chemo-Endocrine Score(CES) in Hormone Receptor-Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 -Based Therapy[J].
Clin Cancer Res.
Published:April 16,2021.
DOI:10.
1158/1078-0432.
CCR-20-4102[2]Naoko Takebe,Abdul Rafeh Naqash,Geraldine O'Sullivan Coyne,et al.
Safety,anti-tumor activity,and biomarker analysis in a phase 1 trial of the once-daily Wee1 inhibitor adavosertib(AZD1775)in patients with advanced solid tumors[J].
Clin Cancer Res.
Published:April 16,2021.
DOI:10.
1158 /1078-0432.
CCR-21-0329[3]https://mp.
weixin.
qq.
com/s/NhJeReBSXvF4-puMPjyvgw[4] ?sn=a66bef65e5b04013b5e9147eb926d55e&from=wechat
New drug: China’s first self-developed ADC drug is expected to be approved for gastric cancer 01CCR: PAM50-based chemical endocrine score can predict the efficacy and prognosis of neoadjuvant treatment for HR+/HER2+ breast cancer.
On April 16, Clinical Cancer Research reported a PAM50-based chemical endocrine score (CES) for hormone receptor positive/ Independent validation analysis of neoadjuvant anti-HER2 combination therapy for HER2-positive (HR+/HER2+) breast cancer showed that CES can effectively predict the chemoendocrine sensitivity and prognosis of HER2+/HR+ breast cancer.
The article release screenshots based on PAM50 CES can predict the chemoendocrine sensitivity of HR+/HER2- breast cancer.
However, it has not been verified whether CES based on PAM50 is a biomarker for predicting the efficacy and prognosis of HR+/HER2+ breast cancer.
This analysis aims to assess the association between CES and HR+/HER2+ breast cancer efficacy and survival.
Include 7 studies on HER2 targeted therapy combined with endocrine therapy (ET) or chemotherapy (CTX) in the treatment of HR+/HER2+ breast cancer patients, and obtain intrinsic subtypes and clinicopathological data from them.
Use CES as a continuous variable—from low to high scores [CES-C (chemically sensitive), CES-U (uncertain), and CES-E (endocrine sensitive)]; first analyze each data set separately, and then Analyze the combined data set.
Multivariate analysis was used to evaluate the association between CES and pathological complete response (pCR) and disease-free survival (DFS).
The results showed that a total of 457 patients were enrolled (112 patients received HER2 targeted therapy + ET and 345 patients received HER2 targeted therapy + CTX).
In the combined cohort, it was found that the proportions of CES-C, CES-U, and CES-E patients were 60%, 23%, and 17%, respectively.
High CES (ie, CES-E) is associated with a lower probability of obtaining pCR, but not with clinical features, treatment, intrinsic subtypes, and research (adjusted OR=0.
42; P=0.
016).
DFS analysis included 295 patients with a median follow-up of 66 months.
High CES was associated with better DFS (adjusted HR=0.
174; P=0.
003), but not with pCR, clinical features, and intrinsic subtypes.
In patients with residual disease, the adjusted DFS HR of CES was 0.
160 (P=0.
012).
The researchers said that for HR+/HER2+ breast cancer, CES can be used to predict chemical endocrine sensitivity, and can provide prognostic predictions beyond intrinsic subtypes and clinicopathological features.
02CCR: Wee1 inhibitor Adavosertib once a day is safe and effective in the treatment of advanced solid tumors.
On April 16, a phase I trial reported by Clinical Cancer Research showed that the Wee1 inhibitor Adavosertib (AZD1775) is safe to treat advanced solid tumors once a day.
,effective.
Article release screenshot Adavosertib can induce cell death.
Previous studies evaluating Adavosertib twice a day for the treatment of patients with advanced solid tumors determined the phase II recommended dose (RPh2D).
This study aims to evaluate the results of Adavosertib once daily.
Using a 3+3 dose escalation design, Adavosertib was administered once a day on Days 1-5 and Days 8-12 of a 21-day cycle.
Molecular biomarkers for Wee1 activity were evaluated in paired tumor biopsies, including Cdk1/2 (pY15-Cdk) phosphorylated at position 15 tyrosine.
Use the remaining tumor tissue to perform whole-exome sequencing and RNA sequencing to identify potential predictive biomarkers.
The results showed that among the 42 patients included, the most common adverse reactions were gastrointestinal and hematological toxicity; dose-limiting toxicity was grade 4 hematological toxicity and grade 3 fatigue.
The RPh2D of Adavosertib once a day is 300 mg.
6 patients (14%) were confirmed to have partial remission (PR): 4 cases of ovarian cancer and 2 cases of endometrial cancer.
The plasma exposure level of Adavosertib once daily is similar to that of twice daily administration.
On the 8th day of the first treatment cycle (before administration), 4 out of 8 patients had tumor pY15-Cdk levels higher than baseline, suggesting that there was a rebound in the therapeutic effect during the administration interruption on days 5-8.
One patient with rapid progression had WEE1 mutation and potential compensatory PKMYT1 overexpression.
Both of the 2 treatment responders had baseline CCNE1 overexpression, one of them had CCNE1 amplification, and none of the 3 non-responders had baseline CCNE1 overexpression.
The researchers said that the study determined the RPh2D of Adavosertib once a day and observed its activity in patients with ovarian cancer or endometrial cancer (including 2 patients with baseline CCNE1 mRNA overexpression).
Future studies will determine whether CCNE1 overexpression is a predictive biomarker of Adavosertib's efficacy.
03 New drug: Nivolumab combined with chemotherapy was approved by the FDA for the first-line treatment of advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma.
On April 17, the US Food and Drug Administration (FDA) announced the approval of PD-1 inhibition Nivolumab is used in combination with chemotherapy as a first-line therapy for advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma.
The press release stated that this is the first first-line immunotherapy approved by the FDA for the treatment of gastric cancer.
The approval is based on the results of a randomized, open-label Phase III clinical trial of CheckMate-649.
A total of 1581 untreated patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma were enrolled.
The results of the trial showed that the combination therapy of nivolumab and chemotherapy significantly improved the overall survival (OS) of patients.
The median OS was 13.
8 months in the nivolumab combination therapy group and 11.
6 months in the chemotherapy group.
Among patients whose tumors express PD-L1 (CPS>5), the nivolumab combined treatment group has a better effect, with a median OS of 14.
4 months and 11.
1 months in the chemotherapy group.
The nivolumab combination therapy group reduced the risk of death by 29% (HR=0.
71, 98.
4%CI 0.
59-0.
86, p<0.
0001).
In China, nivolumab has been approved by the National Medical Products Administration (NMPA) of China in March 2020 for the treatment of advanced or recurrent stomachs or stomachs that have received two or more systemic treatments in the past.
Patients with adenocarcinoma of the esophageal junction.
The main results of the Chinese subgroup of CheckMate-649 show that in the Chinese population, compared with chemotherapy alone, the first-line treatment of unresectable advanced or metastatic gastric cancer and gastroesophageal junction cancer with nivolumab combined with chemotherapy has achieved clinical Significant overall survival and progression-free survival (PFS) benefits.
The analysis results of the Chinese subgroup are consistent with the results of the global population as a whole.
04 New drug: China's first self-developed ADC new drug is expected to be approved for gastric cancer treatment.
On April 19, Rongchang Bio announced: "China's first self-developed antibody-conjugated drug (ADC), a new drug for vedixituzumab, has been approved countdown , Will usher in a new era of targeted tumor therapy".
According to the results of the priority review and publicity of the Center for Drug Evaluation (CDE) of the National Food and Drug Administration of China, the drug is intended to be used to treat HER2 overexpression locally advanced or metastatic gastric cancer (including gastroesophageal cancer) that has received at least 2 system chemotherapy after recurrence/metastasis The marketing application of junction cancer) has been included in the priority review, which means that the drug is about to be approved for gastric cancer.
Screenshot of the CDE official website.
Disitamab vedotin (RC48) is the first anti-HER2 ADC drug in my country to enter clinical research.
It is mainly used for the treatment of advanced or metastatic gastric cancer (GC) and urothelial cancer with HER2 expression.
(UC) and potential treatment of HER2 expression (including low expression) breast cancer patients.
Vidicizumab has been approved by the U.
S.
Food and Drug Administration (FDA) as an orphan drug.
The C008 study of the Phase II clinical trial of Vidicuzumab was conducted by Professor Lin Lin of Peking University Cancer Hospital as the main investigator.
It is a single-arm, single-arm, safety-related study aimed at the effectiveness and safety of HER2 overexpression in patients with locally advanced or metastatic gastric cancer.
The open, multi-center Phase II clinical study is also China's first single-group open clinical study for the third-line treatment of the ADC drug for HER2 overexpressing gastric cancer.
The results of the study showed that the objective response rate (ORR) of the drug in third-line and above HER2 overexpression locally advanced or metastatic gastric cancer reached 23.
6%, the median PFS was 4.
1 months, and the median OS was 7.
6 months.
The patient's survival status Almost as effective as second-line treatment.
Moreover, the study included patients with low HER2 expression, further expanding the target patient population.
In addition, studies have confirmed that it can benefit patients with HER2-expressing breast cancer and biliary tract cancer, as well as some other HER2-expressing solid tumor patients after the failure of conventional treatment.
In the future, it is hoped that the first Chinese self-developed ADC drug Vidicitor Monoclonal antibodies can play a role in the treatment of multiple tumors. References: [1] Tomás Pascual, Aranzazu Fernandez-Martinez, Maki Tanioka, et al.
Independent Validation of the PAM50-Based Chemo-Endocrine Score(CES) in Hormone Receptor-Positive HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 -Based Therapy[J].
Clin Cancer Res.
Published:April 16,2021.
DOI:10.
1158/1078-0432.
CCR-20-4102[2]Naoko Takebe,Abdul Rafeh Naqash,Geraldine O'Sullivan Coyne,et al.
Safety,anti-tumor activity,and biomarker analysis in a phase 1 trial of the once-daily Wee1 inhibitor adavosertib(AZD1775)in patients with advanced solid tumors[J].
Clin Cancer Res.
Published:April 16,2021.
DOI:10.
1158 /1078-0432.
CCR-21-0329[3]https://mp.
weixin.
qq.
com/s/NhJeReBSXvF4-puMPjyvgw[4] ?sn=a66bef65e5b04013b5e9147eb926d55e&from=wechat
