-
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 birth and application of immune checkpoint inhibitors opened a new chapter in the treatment of non-small cell lung cancer (NSCLC)
.
In 2021, the American Association for Cancer Research (AACR) announced the results of the breakthrough study RATIONALE 303 of tislelizumab in the field of NSCLC: Compared with chemotherapy, tislelizumab alone can significantly improve second/third-line NSCLC The overall survival (OS) of the patient, and the safety is good
.
The research results shined on the international stage, further demonstrated the status and value of national innovative drugs, and ignited new hope for many NSCLC patients
.
In this regard, Yimaitong was fortunate to interview one of the main investigators of the RATIONALE 303 study, Professor Wang Ziping from Peking University Cancer Hospital, to introduce us the progress and clinical experience of the RATIONALE 303 study
.
Professor Wang Ziping, Director of the First Department of Thoracic Oncology, Peking University Cancer Hospital, Chief Physician/Professor, China Medical Education Association, Chairman of the Professional Committee of Cancer Chemotherapy, Chinese Society of Gerontology and Geriatrics, Director of the Professional Committee of Oncology and Microbiology, Chinese Society of Gerontology and Geriatrics Member of the Chinese Society of Gerontology and Geriatrics, Geriatric Oncology Professional Committee, Lung Cancer Sub-Committee Deputy Chairman Member of the National Health Professional Technical Qualification Examination Expert Committee Secretary of the Expert Group of Non-small Cell Lung Cancer NCCN China Edition Secretary of the Expert Group of Non-Small Cell Lung Cancer NCCN China Edition Seeking to move forward: looking for hope in a difficult situation.
With the development of medical technology, the treatment of NSCLC has undergone rapid changes.
From traditional chemotherapy to molecular targeted therapy, to today's immunotherapy, the prognosis of patients has gradually improved
.
At present, domestic immunologic drugs have been approved for the first-line treatment of NSCLC, but due to various reasons, such as the availability of drugs, many patients have missed the opportunity of immunotherapy
.
In the past, docetaxel was widely used in clinical practice and was the standard treatment plan for second-line treatment of NSCLC, but patient survival was not ideal
.
For patients who fail to use immunotherapy in the first line, immunotherapy can be tried in the second line
.
However, China’s currently approved immunotherapy drugs are relatively limited, and it is hoped that more drugs will come out to provide patients with more choices
.
Facing the dilemma of the second/third-line treatment of advanced NSCLC, the innovative immunotherapeutic drug tislelizumab independently developed by China has brought revolutionary progress in the clinical treatment of NSCLC
.
"Data is king": RATIONALE 303 research data shines on the international stage, and NSCLC patients’ survival benefits are fully improved.
Professor Wang Ziping introduced that RATIONALE 303 is a randomized, open, multi-center global phase III clinical trial designed to evaluate alternatives.
The effectiveness and safety of ralizumab versus docetaxel in the treatment of second/third-line locally advanced or metastatic NSCLC patients who have undergone disease progression after receiving platinum-based chemotherapy
.
The study enrolled 805 patients in 10 countries around the world, and randomly enrolled them into the tislelizumab monotherapy group or the docetaxel control group at a ratio of 2:1
.
Figure 1 RATIONALE 303 study design Judging from the currently published data, tislelizumab has a very significant clinical benefit compared to traditional chemotherapy: the study has reached the main research endpoint OS in the interim analysis: contrast chemotherapy, Tilelizumab reduces the risk of death by 36%
.
The median OS reached nearly one and a half years (17.
2 months vs.
11.
9 months); the 2-year OS rate reached 1.
6 times that of the chemotherapy group (39.
4% vs.
25.
0%).
Figure 2 OS results of the RATIONALE 303 study regardless of PD-L1 expression Benefits for the entire patient population: Patients with PD-L1 ≥ 1% have a 42% reduction in the risk of death; even for patients with PD-L1 <1%, the risk of death can be reduced by 26%.
Survival benefits can be shown at the beginning of treatment , OS curve has no crossover: Unlike many previous immunotherapy single-agent studies, in the RATIONALE 303 study, the OS curve can be separated at an early stage, and patients can benefit from an objective response rate (ORR) higher than chemotherapy in the early stage of treatment3 Times: The proportion of patients in remission increased to more than 3 times that of the chemotherapy group (21.
9% vs.
7.
0%), and the median duration of remission increased to more than twice that of the chemotherapy group (13.
5 months vs.
6.
2 months).
Figure 3 RATIONALE 303 study The incidence of adverse reactions in the remission situation is generally lower than that of the chemotherapy group, and no new safety signals have appeared: although the treatment cycle of patients in the tislelizumab group is more than twice that of the chemotherapy group (9.
4 cycles vs.
4.
5 cycles), However, the incidence of immune-related adverse reactions is relatively low.
The incidence of treatment-related adverse reactions above grade 3 is only 14%, which is significantly lower than the 66% in the chemotherapy group.
Figure 4 Safety results of the RATIONALE 303 study.
In addition, analysis of previous second-line/third-line studies The main clinical research data (such as the CheckMate 078 study) found that: the median OS of nivolumab was 11.
9 months, which was higher than the chemotherapy group's 9.
5 months (HR=0.
75); ORR was 18%
.
The prospects are infinite: Let the world listen to China's voice, tislelizumab will "endurance" the lives of more NSCLC patients.
At present, in China, only nivolizumab is approved for the treatment of second-line NSCLC, and patients have fewer choices
.
In view of the excellent data of the RATIONALE 303 study, the new indications of tislelizumab for the second/third-line treatment of NSCLC have been accepted by the NMPA, which is expected to fully cover the areas of lung squamous cell carcinoma and non-squamous cell carcinoma, adding another powerful weapon to Chinese clinicians
.
In addition to survival advantages, tislelizumab, as the world's only PD-1 monoclonal antibody with antibody Fc modification, effectively avoids the ADCP effect, minimizes the binding to FcγR of macrophages, and maximizes the number of effector T cells.
And function, improve curative effect while reducing side effects
.
The results of the RATIONALE 303 study have again confirmed the clinical benefits brought by Fc segment modification
.
In addition, Professor Wang introduced that Peking University Cancer Hospital, as one of the research centers of RATIONALE 303 research, has screened 40 subjects in recent years, and 23 of them successfully entered clinical trials
.
Up to now, 6 patients are still receiving treatment, and 1 patient is still under follow-up for survival
.
Professor Wang said that tislelizumab has excellent efficacy and safety during the second/third-line use of NSCLC
.
It is hoped that in the near future, tislelizumab will be quickly approved for new indications, thereby benefiting more NSCLC patients
.
Summary Based on the breakthrough results of the RATIONALE 303 study, tislelizumab has become the world's only PD-1 monoclonal antibody that benefits the entire population of advanced NSCLC first-line or second-line, and the only domestically developed PD-1 monoclonal antibody for lung cancer.
Drugs that have achieved a positive result for the primary end point of OS in a phase III clinical study
.
In the "CSCO Immune Checkpoint Inhibitors Clinical Application Guidelines (2021 Edition)", tislelizumab combined with chemotherapy for first-line treatment of advanced squamous NSCLC was recommended by the guideline I, combined with chemotherapy for first-line treatment of advanced non-squamous driving gene negative NSCLC and single-agent second/third-line treatment of advanced NSCLC are also recommended by the guidelines based on IA evidence
.
We look forward to more national innovative drugs "going abroad and benefiting the world"
.
.
In 2021, the American Association for Cancer Research (AACR) announced the results of the breakthrough study RATIONALE 303 of tislelizumab in the field of NSCLC: Compared with chemotherapy, tislelizumab alone can significantly improve second/third-line NSCLC The overall survival (OS) of the patient, and the safety is good
.
The research results shined on the international stage, further demonstrated the status and value of national innovative drugs, and ignited new hope for many NSCLC patients
.
In this regard, Yimaitong was fortunate to interview one of the main investigators of the RATIONALE 303 study, Professor Wang Ziping from Peking University Cancer Hospital, to introduce us the progress and clinical experience of the RATIONALE 303 study
.
Professor Wang Ziping, Director of the First Department of Thoracic Oncology, Peking University Cancer Hospital, Chief Physician/Professor, China Medical Education Association, Chairman of the Professional Committee of Cancer Chemotherapy, Chinese Society of Gerontology and Geriatrics, Director of the Professional Committee of Oncology and Microbiology, Chinese Society of Gerontology and Geriatrics Member of the Chinese Society of Gerontology and Geriatrics, Geriatric Oncology Professional Committee, Lung Cancer Sub-Committee Deputy Chairman Member of the National Health Professional Technical Qualification Examination Expert Committee Secretary of the Expert Group of Non-small Cell Lung Cancer NCCN China Edition Secretary of the Expert Group of Non-Small Cell Lung Cancer NCCN China Edition Seeking to move forward: looking for hope in a difficult situation.
With the development of medical technology, the treatment of NSCLC has undergone rapid changes.
From traditional chemotherapy to molecular targeted therapy, to today's immunotherapy, the prognosis of patients has gradually improved
.
At present, domestic immunologic drugs have been approved for the first-line treatment of NSCLC, but due to various reasons, such as the availability of drugs, many patients have missed the opportunity of immunotherapy
.
In the past, docetaxel was widely used in clinical practice and was the standard treatment plan for second-line treatment of NSCLC, but patient survival was not ideal
.
For patients who fail to use immunotherapy in the first line, immunotherapy can be tried in the second line
.
However, China’s currently approved immunotherapy drugs are relatively limited, and it is hoped that more drugs will come out to provide patients with more choices
.
Facing the dilemma of the second/third-line treatment of advanced NSCLC, the innovative immunotherapeutic drug tislelizumab independently developed by China has brought revolutionary progress in the clinical treatment of NSCLC
.
"Data is king": RATIONALE 303 research data shines on the international stage, and NSCLC patients’ survival benefits are fully improved.
Professor Wang Ziping introduced that RATIONALE 303 is a randomized, open, multi-center global phase III clinical trial designed to evaluate alternatives.
The effectiveness and safety of ralizumab versus docetaxel in the treatment of second/third-line locally advanced or metastatic NSCLC patients who have undergone disease progression after receiving platinum-based chemotherapy
.
The study enrolled 805 patients in 10 countries around the world, and randomly enrolled them into the tislelizumab monotherapy group or the docetaxel control group at a ratio of 2:1
.
Figure 1 RATIONALE 303 study design Judging from the currently published data, tislelizumab has a very significant clinical benefit compared to traditional chemotherapy: the study has reached the main research endpoint OS in the interim analysis: contrast chemotherapy, Tilelizumab reduces the risk of death by 36%
.
The median OS reached nearly one and a half years (17.
2 months vs.
11.
9 months); the 2-year OS rate reached 1.
6 times that of the chemotherapy group (39.
4% vs.
25.
0%).
Figure 2 OS results of the RATIONALE 303 study regardless of PD-L1 expression Benefits for the entire patient population: Patients with PD-L1 ≥ 1% have a 42% reduction in the risk of death; even for patients with PD-L1 <1%, the risk of death can be reduced by 26%.
Survival benefits can be shown at the beginning of treatment , OS curve has no crossover: Unlike many previous immunotherapy single-agent studies, in the RATIONALE 303 study, the OS curve can be separated at an early stage, and patients can benefit from an objective response rate (ORR) higher than chemotherapy in the early stage of treatment3 Times: The proportion of patients in remission increased to more than 3 times that of the chemotherapy group (21.
9% vs.
7.
0%), and the median duration of remission increased to more than twice that of the chemotherapy group (13.
5 months vs.
6.
2 months).
Figure 3 RATIONALE 303 study The incidence of adverse reactions in the remission situation is generally lower than that of the chemotherapy group, and no new safety signals have appeared: although the treatment cycle of patients in the tislelizumab group is more than twice that of the chemotherapy group (9.
4 cycles vs.
4.
5 cycles), However, the incidence of immune-related adverse reactions is relatively low.
The incidence of treatment-related adverse reactions above grade 3 is only 14%, which is significantly lower than the 66% in the chemotherapy group.
Figure 4 Safety results of the RATIONALE 303 study.
In addition, analysis of previous second-line/third-line studies The main clinical research data (such as the CheckMate 078 study) found that: the median OS of nivolumab was 11.
9 months, which was higher than the chemotherapy group's 9.
5 months (HR=0.
75); ORR was 18%
.
The prospects are infinite: Let the world listen to China's voice, tislelizumab will "endurance" the lives of more NSCLC patients.
At present, in China, only nivolizumab is approved for the treatment of second-line NSCLC, and patients have fewer choices
.
In view of the excellent data of the RATIONALE 303 study, the new indications of tislelizumab for the second/third-line treatment of NSCLC have been accepted by the NMPA, which is expected to fully cover the areas of lung squamous cell carcinoma and non-squamous cell carcinoma, adding another powerful weapon to Chinese clinicians
.
In addition to survival advantages, tislelizumab, as the world's only PD-1 monoclonal antibody with antibody Fc modification, effectively avoids the ADCP effect, minimizes the binding to FcγR of macrophages, and maximizes the number of effector T cells.
And function, improve curative effect while reducing side effects
.
The results of the RATIONALE 303 study have again confirmed the clinical benefits brought by Fc segment modification
.
In addition, Professor Wang introduced that Peking University Cancer Hospital, as one of the research centers of RATIONALE 303 research, has screened 40 subjects in recent years, and 23 of them successfully entered clinical trials
.
Up to now, 6 patients are still receiving treatment, and 1 patient is still under follow-up for survival
.
Professor Wang said that tislelizumab has excellent efficacy and safety during the second/third-line use of NSCLC
.
It is hoped that in the near future, tislelizumab will be quickly approved for new indications, thereby benefiting more NSCLC patients
.
Summary Based on the breakthrough results of the RATIONALE 303 study, tislelizumab has become the world's only PD-1 monoclonal antibody that benefits the entire population of advanced NSCLC first-line or second-line, and the only domestically developed PD-1 monoclonal antibody for lung cancer.
Drugs that have achieved a positive result for the primary end point of OS in a phase III clinical study
.
In the "CSCO Immune Checkpoint Inhibitors Clinical Application Guidelines (2021 Edition)", tislelizumab combined with chemotherapy for first-line treatment of advanced squamous NSCLC was recommended by the guideline I, combined with chemotherapy for first-line treatment of advanced non-squamous driving gene negative NSCLC and single-agent second/third-line treatment of advanced NSCLC are also recommended by the guidelines based on IA evidence
.
We look forward to more national innovative drugs "going abroad and benefiting the world"
.