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Author: Cornflower This article is published by Yimaitong authorized by the author, please do not reprint without authorization.
The 2021 American Society of Clinical Oncology (ASCO) Annual Meeting will be held online from June 4th to 8th.
As one of the largest and most popular events in the oncology community, the ASCO Annual Meeting will show scholars from all walks of life the latest cutting-edge progress.
At present, most of the abstracts have been published on the official website.
What are the important research advances in the area of lung cancer that will be the most concerned this year? Come and watch.
EGFR targets 1.
New advances in first-line treatment of EGFR.
Ametinib is the first-line treatment for patients with epidermal growth factor receptor (EGFR) mutant lung cancer, with a median progression-free survival (mPFS) of 19.
3 months (Abstr 9013).
Ametinib is the first in my country A self-developed third-generation EGFR tyrosine kinase inhibitor (TKI) for the second-line treatment of T790M mutation-positive non-small cell lung cancer (NSCLC) patients.
The results of the Phase III AENEAS study will be announced at this meeting, which strongly proves the benefits of its first-line treatment.
A total of 429 patients with advanced NSCLC with EGFR19 exon deletion or L858R mutation were enrolled in the study, and they were randomized 1:1 to receive treatment with ametinib or gefitinib.
The results of the study showed that compared with gefitinib, patients who used ametinib as the first-line treatment had significantly longer PFS and duration of remission (DOR)-mPFS 19.
3 months vs 9.
9 months (HR0.
46, P< 0.
0001), mDOR 18.
1 months vs 8.
3 months (HR 0.
38, P<0.
0001).
In terms of safety, the ametinib group is safe and controllable.
2.
New development of EGFR 20ins DZD9008 is used for NSCLC patients with EGFR 20ins insertion mutation (EGFR 20ins), the disease control rate (DCR) is as high as 90.
3% (Abstr 9008) DZD9008 is a small molecule designed for EGFR/HER2 20ins mutation Compound.
In the study reported at this meeting, 97 cases of NSCLC with EGFR/HER2 mutations were included, and the dose of DZD9008 was 50 mg to 400 mg.
The results showed that the best tolerated dose of DZD9008 was 400 mg, and the common grade 3 adverse reactions were diarrhea (5.
2%) and rash (1%).
Fifty-six patients (42.
9% of patients with brain metastases) underwent efficacy evaluation.
When the dose of DZD9008 was 300 mg once a day, the objective response rate (ORR) was 48.
4% (15/31), and the DCR was 90.
3% (28/31).
3.
New progress in EGFR resistance, HER3-targeted antibody conjugated drug (ADC) patritumab deruxtecan (U3-1402) after the line treatment of EGFR-TKI-resistant NSCLC patients, the DCR is 72% (Abstr 9007) will soon be at this meeting In the published phase I study of dose escalation/cohort expansion, 53 patients with locally advanced or metastatic NSCLC with EGFR mutations who had previously received EGFR-TKI treatment were included, and the median number of treatment lines was 4.
All patients received patritumab deruxtecan (U3-1402, 5.
6 mg/kg) Q3W treatment, and the median follow-up was 10.
2 months.
The results showed that the primary study endpoint ORR was 39% (1 CR, 21 PR), and DCR was 72%.
Among them, patients who had previously received platinum-containing chemotherapy had an ORR of 37%; patients who had previously received osimertinib and platinum-containing chemotherapy had an ORR of 39%, a median DOR of 6.
9 months, and a median PFS of 8.
2 months. The most common ≥ grade 3 adverse events were thrombocytopenia (30%), neutral neuropenia (19%) and fatigue (14%).
KRAS target Sorasasib can benefit patients with co-mutated KRAS p.
G12 C mutant NSCLC (Abstr 9003) Sorasasib (AMG510) is a small molecule inhibitor that can selectively and irreversibly target KRAS p.
G12C.
The CodeBreaK 100 study included 129 patients (59 cases of NSCLC, 42 cases of colorectal cancer and 28 cases of other tumors).
Previous studies have shown that the ORR of sorasasib in the treatment of NSCLC patients with KRAS G12C mutations was 37.
1% and the PFS was 6.
8 month.
This time ASCO reported the results of the subgroup analysis of ORR.
Among them, for patients who have not received immunotherapy, the use of KRAS inhibitors has better benefits, with an ORR of 45.
5%; for patients with lung cancer with co-mutation of KRAS and TP53, ORR is 39.
3%; for patients with lung cancer with co-mutation of KRAS and STK11, ORR 40%; for lung cancer patients with co-mutation of KRAS and KEAP1, ORR was 20%.
MET mutation Capmatinib treats NSCLC patients with MET 14 exon skipping mutation (MET ex14), the first-line treatment is more effective (Abstr 9020) MET amplification (METamp) is a carcinogenic driver that occurs in 1%-5% of NSCLC Among them, the prognosis is poor and there is a lack of approved targeted therapies.
Capmatinib is a selective MET inhibitor, based on a multi-cohort phase II GEOMETRY mono-1 study, and has been approved in the United States and Japan for the treatment of advanced NSCLC patients with MET ex14.
This time ASCO reported 160 untreated MET ex14 NSCLC patients (groups 5b and 7) and patients who had previously received first-line or second-line treatment (expansion group 6 and cohort 4).
The ORR of the extended cohort 7 was 65.
6%, the median PFS was 10.
8 months, and the median overall survival (OS) was immature.
The ORR of cohort 5b was 67.
9%, OS was 20.
8 months, and median PFS was 12.
4 months.
Capmatinib treatment of MET ex14 NSCLC patients, ORR is 40.
6%, OS is 13.
6 months, so capmatinib first-line treatment can benefit more.
ROS1 mutation ROS1 mutation: After crizotinib is treated with brigatinib treatment, DCR is nearly 60% (Abstr 9040), about 2% of NSCLC patients, and 3.
3% of lung adenocarcinoma patients will have ROS1 fusion.
Brigatinib is a new generation TKI targeting ALK and ROS1.
Crizotinib is the first drug approved for the treatment of ROS1 fusion-positive NSCLC.
The standard treatment for crizotinib-resistant ROS1-positive NSCLC has not yet been established.
The Barossa trial is a multicenter, phase II basket study in patients with ROS1-positive solid tumors.
This ASCO reports the results of the study of ROS1-positive NSCLC patients who have previously received crizotinib treatment (cohort 2).
The enrolled patients received brigatinib 180 mg once a day, the lead-in period was 7 days, and the dose was 90 mg.
At the data cutoff date of October 30, 2020, 5 and 6 patients had achieved partial remission (PR) and stable disease (SD), respectively.
ORR was 26.
3% (90%CI 11.
0-47.
6), and DCR was 57.
9% (95%CI 33.
5-79.
7).
The median follow-up duration of PFS was 12.
0 months.
The median PFS was 7.
3 months (95%CI 1.
3-9.
3), and the 1-year PFS rate was 26.
9% (95%CI 9.
2-48.
6). TROP2 target TROP 2 ADC ——DS-1062 (Datopotamab deruxtecan, Dato-DXd) in the treatment of advanced NSCLC, ORR is 25% (Abstr 9058) TROP2 is a transmembrane glycoprotein, which is used in a variety of solid tumors including NSCLC Highly expressed in both.
DS-1062 is an ADC targeting TROP2.
TROPION-PanTumor01 is a multicenter dose escalation/expansion study to evaluate the efficacy and safety of Dato-DXd Q3W administration in patients with advanced NSCLC.
The results of the study showed that the median follow-up time was 7.
4 months (range: 0.
10-21.
7 months), the incidence of all grades of treatment-related adverse events selected in the 8 mg/kg cohort, ≥ grade 3 drug-related adverse events, and serious drugs The incidence of related adverse events, the incidence of drug-related interstitial lung disease (ILD), and the proportion of patients who discontinued treatment early due to adverse events were higher than those in the 4 mg/kg and 6 mg/kg dose groups.
The ORR determined by blind independent central review was similar: 25% (20/80) for the 8 mg/kg cohort; 21% (8/39) for the 6 mg/kg cohort; 23% (9/40) for the 4 mg/kg cohort.
The initial mPFS (95%CI) of the 8 mg/kg cohort was 5.
4 months (4.
1-7.
1 months), the 6 mg/kg cohort was 8.
2 months (1.
5-11.
8 months), and the 4 mg/kg cohort was 4.
3 months (2.
0 months-NE).
HER2 20ins mutation combined with anti-HER2 therapy has become a reference strategy for patients with HER2-positive metastatic NSCLC (Abstr 9015) The incidence of HER2 gene 20 exon insertion mutation (HER2 20ins) in NSCLC is 1%-2%, and there is currently no target Approved therapy for these patients.
IFCT-1703 R2D2 is a multi-center, non-randomized phase II clinical trial that included 45 patients with HER2 20ins who had previously received chemotherapy and 31.
1% of them had brain metastases. These patients were treated with trastuzumab + pertuzumab + docetaxel.
A median follow-up of 12 months, 44 patients can be evaluated for efficacy.
ORR was 29%, DCR was 85%, mPFS was 6.
8 months, and the incidence of grade 3-4 adverse reactions was 64%.
RET fusion Selpercatinib is effective in RET fusion-positive NSCLC patients (Abstr 9032).
About 1%~2% of NSCLC patients will have RET gene fusion.
Selpercatinib is the first highly selective, potent, CNS (central nervous system) active RET kinase inhibitor.
The LIBRETTO-001 study is a phase I-II clinical trial conducted in 89 research centers in 16 countries to evaluate the efficacy of selpercatinib in previously treated RET fusion-positive NSCLC patients.
A total of 218 patients who had previously received platinum-based chemotherapy and whose efficacy could be evaluated were included.
The results showed that among the evaluable patients (N=218) who had previously received platinum-based chemotherapy, 57% of the patients responded to selpercatinib, and 16% of the patients responded to the previous immediate treatment.
Regardless of previous treatment, improvement in ORR after selpercatinib treatment was observed: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%) or chemotherapy (58% vs 15%) ).
A total of 108 patients (49%) did not respond to previous immediate treatment, but responded to selpercatinib.
The follow-up editor will bring you more ASCO progress, and let us experience the latest developments and breakthroughs in clinical research in the global oncology field.
The 2021 American Society of Clinical Oncology (ASCO) Annual Meeting will be held online from June 4th to 8th.
As one of the largest and most popular events in the oncology community, the ASCO Annual Meeting will show scholars from all walks of life the latest cutting-edge progress.
At present, most of the abstracts have been published on the official website.
What are the important research advances in the area of lung cancer that will be the most concerned this year? Come and watch.
EGFR targets 1.
New advances in first-line treatment of EGFR.
Ametinib is the first-line treatment for patients with epidermal growth factor receptor (EGFR) mutant lung cancer, with a median progression-free survival (mPFS) of 19.
3 months (Abstr 9013).
Ametinib is the first in my country A self-developed third-generation EGFR tyrosine kinase inhibitor (TKI) for the second-line treatment of T790M mutation-positive non-small cell lung cancer (NSCLC) patients.
The results of the Phase III AENEAS study will be announced at this meeting, which strongly proves the benefits of its first-line treatment.
A total of 429 patients with advanced NSCLC with EGFR19 exon deletion or L858R mutation were enrolled in the study, and they were randomized 1:1 to receive treatment with ametinib or gefitinib.
The results of the study showed that compared with gefitinib, patients who used ametinib as the first-line treatment had significantly longer PFS and duration of remission (DOR)-mPFS 19.
3 months vs 9.
9 months (HR0.
46, P< 0.
0001), mDOR 18.
1 months vs 8.
3 months (HR 0.
38, P<0.
0001).
In terms of safety, the ametinib group is safe and controllable.
2.
New development of EGFR 20ins DZD9008 is used for NSCLC patients with EGFR 20ins insertion mutation (EGFR 20ins), the disease control rate (DCR) is as high as 90.
3% (Abstr 9008) DZD9008 is a small molecule designed for EGFR/HER2 20ins mutation Compound.
In the study reported at this meeting, 97 cases of NSCLC with EGFR/HER2 mutations were included, and the dose of DZD9008 was 50 mg to 400 mg.
The results showed that the best tolerated dose of DZD9008 was 400 mg, and the common grade 3 adverse reactions were diarrhea (5.
2%) and rash (1%).
Fifty-six patients (42.
9% of patients with brain metastases) underwent efficacy evaluation.
When the dose of DZD9008 was 300 mg once a day, the objective response rate (ORR) was 48.
4% (15/31), and the DCR was 90.
3% (28/31).
3.
New progress in EGFR resistance, HER3-targeted antibody conjugated drug (ADC) patritumab deruxtecan (U3-1402) after the line treatment of EGFR-TKI-resistant NSCLC patients, the DCR is 72% (Abstr 9007) will soon be at this meeting In the published phase I study of dose escalation/cohort expansion, 53 patients with locally advanced or metastatic NSCLC with EGFR mutations who had previously received EGFR-TKI treatment were included, and the median number of treatment lines was 4.
All patients received patritumab deruxtecan (U3-1402, 5.
6 mg/kg) Q3W treatment, and the median follow-up was 10.
2 months.
The results showed that the primary study endpoint ORR was 39% (1 CR, 21 PR), and DCR was 72%.
Among them, patients who had previously received platinum-containing chemotherapy had an ORR of 37%; patients who had previously received osimertinib and platinum-containing chemotherapy had an ORR of 39%, a median DOR of 6.
9 months, and a median PFS of 8.
2 months. The most common ≥ grade 3 adverse events were thrombocytopenia (30%), neutral neuropenia (19%) and fatigue (14%).
KRAS target Sorasasib can benefit patients with co-mutated KRAS p.
G12 C mutant NSCLC (Abstr 9003) Sorasasib (AMG510) is a small molecule inhibitor that can selectively and irreversibly target KRAS p.
G12C.
The CodeBreaK 100 study included 129 patients (59 cases of NSCLC, 42 cases of colorectal cancer and 28 cases of other tumors).
Previous studies have shown that the ORR of sorasasib in the treatment of NSCLC patients with KRAS G12C mutations was 37.
1% and the PFS was 6.
8 month.
This time ASCO reported the results of the subgroup analysis of ORR.
Among them, for patients who have not received immunotherapy, the use of KRAS inhibitors has better benefits, with an ORR of 45.
5%; for patients with lung cancer with co-mutation of KRAS and TP53, ORR is 39.
3%; for patients with lung cancer with co-mutation of KRAS and STK11, ORR 40%; for lung cancer patients with co-mutation of KRAS and KEAP1, ORR was 20%.
MET mutation Capmatinib treats NSCLC patients with MET 14 exon skipping mutation (MET ex14), the first-line treatment is more effective (Abstr 9020) MET amplification (METamp) is a carcinogenic driver that occurs in 1%-5% of NSCLC Among them, the prognosis is poor and there is a lack of approved targeted therapies.
Capmatinib is a selective MET inhibitor, based on a multi-cohort phase II GEOMETRY mono-1 study, and has been approved in the United States and Japan for the treatment of advanced NSCLC patients with MET ex14.
This time ASCO reported 160 untreated MET ex14 NSCLC patients (groups 5b and 7) and patients who had previously received first-line or second-line treatment (expansion group 6 and cohort 4).
The ORR of the extended cohort 7 was 65.
6%, the median PFS was 10.
8 months, and the median overall survival (OS) was immature.
The ORR of cohort 5b was 67.
9%, OS was 20.
8 months, and median PFS was 12.
4 months.
Capmatinib treatment of MET ex14 NSCLC patients, ORR is 40.
6%, OS is 13.
6 months, so capmatinib first-line treatment can benefit more.
ROS1 mutation ROS1 mutation: After crizotinib is treated with brigatinib treatment, DCR is nearly 60% (Abstr 9040), about 2% of NSCLC patients, and 3.
3% of lung adenocarcinoma patients will have ROS1 fusion.
Brigatinib is a new generation TKI targeting ALK and ROS1.
Crizotinib is the first drug approved for the treatment of ROS1 fusion-positive NSCLC.
The standard treatment for crizotinib-resistant ROS1-positive NSCLC has not yet been established.
The Barossa trial is a multicenter, phase II basket study in patients with ROS1-positive solid tumors.
This ASCO reports the results of the study of ROS1-positive NSCLC patients who have previously received crizotinib treatment (cohort 2).
The enrolled patients received brigatinib 180 mg once a day, the lead-in period was 7 days, and the dose was 90 mg.
At the data cutoff date of October 30, 2020, 5 and 6 patients had achieved partial remission (PR) and stable disease (SD), respectively.
ORR was 26.
3% (90%CI 11.
0-47.
6), and DCR was 57.
9% (95%CI 33.
5-79.
7).
The median follow-up duration of PFS was 12.
0 months.
The median PFS was 7.
3 months (95%CI 1.
3-9.
3), and the 1-year PFS rate was 26.
9% (95%CI 9.
2-48.
6). TROP2 target TROP 2 ADC ——DS-1062 (Datopotamab deruxtecan, Dato-DXd) in the treatment of advanced NSCLC, ORR is 25% (Abstr 9058) TROP2 is a transmembrane glycoprotein, which is used in a variety of solid tumors including NSCLC Highly expressed in both.
DS-1062 is an ADC targeting TROP2.
TROPION-PanTumor01 is a multicenter dose escalation/expansion study to evaluate the efficacy and safety of Dato-DXd Q3W administration in patients with advanced NSCLC.
The results of the study showed that the median follow-up time was 7.
4 months (range: 0.
10-21.
7 months), the incidence of all grades of treatment-related adverse events selected in the 8 mg/kg cohort, ≥ grade 3 drug-related adverse events, and serious drugs The incidence of related adverse events, the incidence of drug-related interstitial lung disease (ILD), and the proportion of patients who discontinued treatment early due to adverse events were higher than those in the 4 mg/kg and 6 mg/kg dose groups.
The ORR determined by blind independent central review was similar: 25% (20/80) for the 8 mg/kg cohort; 21% (8/39) for the 6 mg/kg cohort; 23% (9/40) for the 4 mg/kg cohort.
The initial mPFS (95%CI) of the 8 mg/kg cohort was 5.
4 months (4.
1-7.
1 months), the 6 mg/kg cohort was 8.
2 months (1.
5-11.
8 months), and the 4 mg/kg cohort was 4.
3 months (2.
0 months-NE).
HER2 20ins mutation combined with anti-HER2 therapy has become a reference strategy for patients with HER2-positive metastatic NSCLC (Abstr 9015) The incidence of HER2 gene 20 exon insertion mutation (HER2 20ins) in NSCLC is 1%-2%, and there is currently no target Approved therapy for these patients.
IFCT-1703 R2D2 is a multi-center, non-randomized phase II clinical trial that included 45 patients with HER2 20ins who had previously received chemotherapy and 31.
1% of them had brain metastases. These patients were treated with trastuzumab + pertuzumab + docetaxel.
A median follow-up of 12 months, 44 patients can be evaluated for efficacy.
ORR was 29%, DCR was 85%, mPFS was 6.
8 months, and the incidence of grade 3-4 adverse reactions was 64%.
RET fusion Selpercatinib is effective in RET fusion-positive NSCLC patients (Abstr 9032).
About 1%~2% of NSCLC patients will have RET gene fusion.
Selpercatinib is the first highly selective, potent, CNS (central nervous system) active RET kinase inhibitor.
The LIBRETTO-001 study is a phase I-II clinical trial conducted in 89 research centers in 16 countries to evaluate the efficacy of selpercatinib in previously treated RET fusion-positive NSCLC patients.
A total of 218 patients who had previously received platinum-based chemotherapy and whose efficacy could be evaluated were included.
The results showed that among the evaluable patients (N=218) who had previously received platinum-based chemotherapy, 57% of the patients responded to selpercatinib, and 16% of the patients responded to the previous immediate treatment.
Regardless of previous treatment, improvement in ORR after selpercatinib treatment was observed: chemotherapy + immune checkpoint inhibitor (ICI) (57% vs 14%), single-agent ICI (48% vs 3%) or chemotherapy (58% vs 15%) ).
A total of 108 patients (49%) did not respond to previous immediate treatment, but responded to selpercatinib.
The follow-up editor will bring you more ASCO progress, and let us experience the latest developments and breakthroughs in clinical research in the global oncology field.
