Milestone Approval: BMS’s Dual Immunotherapy Opdivo® + Yervoy® Approved in China as First-Line Treatment for Malignant Pleural Mesothelioma
Jun 11, 2021 16:30
CST Updated
16:30
Bristol-Myers Squibb
Biopharmaceutical and Nutritional Product R&D and Sales
On June 11, 2021, Bristol-Myers Squibb announced that nivolumab injection in combination with ipilimumab injection has been approved by China's National Medical Products Administration for adult patients with unresectable, treatment-naïve non-epithelioid malignant pleural mesothelioma. This marks the first indication approved in China for a dual immunotherapy combination, signifying the official launch of Yervoy, the world's first CTLA-4 inhibitor, in China.
This approval is based on the CheckMate-743 clinical study, which is the first and currently only randomized, Phase III clinical trial to demonstrate that first-line dual immunotherapy compared with standard platinum-based chemotherapy provides a survival benefit for all patients with malignant pleural mesothelioma (MPM). Study results showed that at a minimum follow-up of 22 months, the median OS in the overall population was 18.1 months in the dual immunotherapy group versus 14.1 months in the chemotherapy group (hazard ratio [HR]: 0.74 [96.6% confidence interval]: 0.60, 0.91; p=0.002). The 2-year survival rate was 41% in the Opdivo plus ipilimumab group and 27% in the chemotherapy group.
Histological subtype is a well-established prognostic factor in malignant pleural mesothelioma, with the non-epithelioid subtype generally associated with a poorer prognosis. In the CheckMate-743 trial, patients were randomized and stratified by histological subtype. Treatment with Opdivo plus Yervoy improved survival in both non-epithelioid and epithelioid mesothelioma patients, with a more pronounced benefit observed in the non-epithelioid subgroup. In the dual immunotherapy combination arm, the median OS for patients with non-epithelioid histology was 18.1 months, compared with only 8.8 months in the corresponding chemotherapy arm (Hazard Ratio [HR]: 0.46 [95% Confidence Interval]: 0.31, 0.68).
Mesothelioma is a rare and highly aggressive malignant tumor originating from mesothelial cells.Tumor, in China, approximately 3,000 confirmed cases are reported annually, predominantly pleural mesothelioma. Its incidence is highly associated with asbestos exposure. Due toDiagnosisDue to diagnostic delays, most patients present with advanced or metastatic disease at the time of diagnosis. The prognosis for malignant pleural mesothelioma is generally poor, with a median survival of 12 to 14 months and a five-year survival rate of approximately 10% among previously untreated patients with advanced or metastatic malignant pleural mesothelioma.
The China Principal Investigator for CheckMate-743 is affiliated with Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine.TumorDepartment Director Professor Lu Shun. Professor Lu Shun stated that malignant pleural mesothelioma is a highly aggressive rare cancer with very limited treatment options. Its incidence is highly correlated with asbestos exposure, and the majority of patients are diagnosed at an advanced stage, with a 5-year survival rate of less than 10%. Among all histological subtypes, patients with non-epithelioid histology have a poorer prognosis, underscoring an urgent need for novel therapeutic regimens to improve clinical outcomes and prolong survival. As the first approved systemic therapy in 15 years, Opdivo in combination with Yervoy has delivered a twofold overall survival benefit compared to chemotherapy for patients with non-epithelioid histology, making long-term survival possible. This represents a milestone achievement and is poised to become the new standard of care for malignant pleural mesothelioma.
In the newly published 《China ClinicalTumorIn the 《CSCO Guidelines for the Clinical Application of Immune Checkpoint Inhibitors (2021 Edition)》, Opdivo in combination with Yervoy as first-line treatment for non-epithelioid and epithelioid pleural mesothelioma is the only treatment regimen to receive a Class I recommendation (Category 1 evidence) and a Class II recommendation (Category 2A evidence).
The combination of Nivolumab Injection and Ipilimumab Injection is a unique combination of two immune checkpoint inhibitors that target two distinct checkpoints (PD-1 and CTLA-4) respectively to help destroy tumor cells. The two exhibit a potential synergistic mechanism of action: YERVOY promotes the activation and proliferation of T cells, while OPDIVO helps existing T cells recognize tumor cells. A subset of the T cells activated by YERVOY can also differentiate into memory T cells, helping to achieve long-term anti-TumorImmune response.
The combination of nivolumab injection and ipilimumab injection delivers a significant and durable overall survival benefit to patients with advanced malignant pleural mesothelioma through potential synergistic effects, making a "chemotherapy-free" approach possible. Prof. Wu Yilong, Lifetime Director of Guangdong Provincial People's Hospital and Honorary Director of the Guangdong Lung Cancer Institute (GLCI), stated that in the CheckMate-743 trial, the safety profile of Opdivo (3 mg/kg every 2 weeks) combined with Yervoy (1 mg/kg every 6 weeks) as first-line treatment for malignant pleural mesothelioma is consistent with that of this combination in prior studies across other tumor types, including first-line dual immunotherapy for lung cancer. This achieves a balance between efficacy and safety, indicating that dual immunotherapy combination therapy holds the potential to benefit Chinese patients across various tumor indications in the future.
Ms. Siyuan Chen, General Manager of Bristol-Myers Squibb for Mainland China and Hong Kong, stated that Bristol-Myers Squibb has consistently been committed to accelerating the launch of globally innovative drugs in China. Following the launch in China of its first PD-1 inhibitor, ’Opdivo’, Bristol-Myers Squibb has once again brought the world’s first CTLA-4 inhibitor, ’Yervoy’, to China, continuously transforming patients’ lives through science. In the future, Bristol-Myers Squibb will continue to explore immune# Tumorthe application of treatment across various tumor types, including combination immunotherapy, with the aim of providing patients with new therapeutic options. Meanwhile, we will continuously explore collaborations with the Chinese government, payers, and third-party organizations, and through innovative market access models and diversified initiatives, jointly enhance the accessibility of dual immunotherapy in China.”
It is reported that in October 2015, Opdivo in combination with Yervoy became the world's first regulatory authority-approved immunotherapyTumorCombination therapy has currently been approved for 6 tumor types in over 50 countries and regions worldwide, covering lung cancer, pleural mesothelioma,`Melanoma`, kidney cancer, colorectal cancer,Liver Cancer。
This approval is based on the CheckMate-743 clinical study, which is the first and currently only randomized, Phase III clinical trial to demonstrate that first-line dual immunotherapy compared with standard platinum-based chemotherapy provides a survival benefit for all patients with malignant pleural mesothelioma (MPM). Study results showed that at a minimum follow-up of 22 months, the median OS in the overall population was 18.1 months in the dual immunotherapy group versus 14.1 months in the chemotherapy group (hazard ratio [HR]: 0.74 [96.6% confidence interval]: 0.60, 0.91; p=0.002). The 2-year survival rate was 41% in the Opdivo plus ipilimumab group and 27% in the chemotherapy group.
Histological subtype is a well-established prognostic factor in malignant pleural mesothelioma, with the non-epithelioid subtype generally associated with a poorer prognosis. In the CheckMate-743 trial, patients were randomized and stratified by histological subtype. Treatment with Opdivo plus Yervoy improved survival in both non-epithelioid and epithelioid mesothelioma patients, with a more pronounced benefit observed in the non-epithelioid subgroup. In the dual immunotherapy combination arm, the median OS for patients with non-epithelioid histology was 18.1 months, compared with only 8.8 months in the corresponding chemotherapy arm (Hazard Ratio [HR]: 0.46 [95% Confidence Interval]: 0.31, 0.68).
Mesothelioma is a rare and highly aggressive malignant tumor originating from mesothelial cells.Tumor, in China, approximately 3,000 confirmed cases are reported annually, predominantly pleural mesothelioma. Its incidence is highly associated with asbestos exposure. Due toDiagnosisDue to diagnostic delays, most patients present with advanced or metastatic disease at the time of diagnosis. The prognosis for malignant pleural mesothelioma is generally poor, with a median survival of 12 to 14 months and a five-year survival rate of approximately 10% among previously untreated patients with advanced or metastatic malignant pleural mesothelioma.
The China Principal Investigator for CheckMate-743 is affiliated with Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine.TumorDepartment Director Professor Lu Shun. Professor Lu Shun stated that malignant pleural mesothelioma is a highly aggressive rare cancer with very limited treatment options. Its incidence is highly correlated with asbestos exposure, and the majority of patients are diagnosed at an advanced stage, with a 5-year survival rate of less than 10%. Among all histological subtypes, patients with non-epithelioid histology have a poorer prognosis, underscoring an urgent need for novel therapeutic regimens to improve clinical outcomes and prolong survival. As the first approved systemic therapy in 15 years, Opdivo in combination with Yervoy has delivered a twofold overall survival benefit compared to chemotherapy for patients with non-epithelioid histology, making long-term survival possible. This represents a milestone achievement and is poised to become the new standard of care for malignant pleural mesothelioma.
In the newly published 《China ClinicalTumorIn the 《CSCO Guidelines for the Clinical Application of Immune Checkpoint Inhibitors (2021 Edition)》, Opdivo in combination with Yervoy as first-line treatment for non-epithelioid and epithelioid pleural mesothelioma is the only treatment regimen to receive a Class I recommendation (Category 1 evidence) and a Class II recommendation (Category 2A evidence).
The combination of Nivolumab Injection and Ipilimumab Injection is a unique combination of two immune checkpoint inhibitors that target two distinct checkpoints (PD-1 and CTLA-4) respectively to help destroy tumor cells. The two exhibit a potential synergistic mechanism of action: YERVOY promotes the activation and proliferation of T cells, while OPDIVO helps existing T cells recognize tumor cells. A subset of the T cells activated by YERVOY can also differentiate into memory T cells, helping to achieve long-term anti-TumorImmune response.
The combination of nivolumab injection and ipilimumab injection delivers a significant and durable overall survival benefit to patients with advanced malignant pleural mesothelioma through potential synergistic effects, making a "chemotherapy-free" approach possible. Prof. Wu Yilong, Lifetime Director of Guangdong Provincial People's Hospital and Honorary Director of the Guangdong Lung Cancer Institute (GLCI), stated that in the CheckMate-743 trial, the safety profile of Opdivo (3 mg/kg every 2 weeks) combined with Yervoy (1 mg/kg every 6 weeks) as first-line treatment for malignant pleural mesothelioma is consistent with that of this combination in prior studies across other tumor types, including first-line dual immunotherapy for lung cancer. This achieves a balance between efficacy and safety, indicating that dual immunotherapy combination therapy holds the potential to benefit Chinese patients across various tumor indications in the future.
Ms. Siyuan Chen, General Manager of Bristol-Myers Squibb for Mainland China and Hong Kong, stated that Bristol-Myers Squibb has consistently been committed to accelerating the launch of globally innovative drugs in China. Following the launch in China of its first PD-1 inhibitor, ’Opdivo’, Bristol-Myers Squibb has once again brought the world’s first CTLA-4 inhibitor, ’Yervoy’, to China, continuously transforming patients’ lives through science. In the future, Bristol-Myers Squibb will continue to explore immune# Tumorthe application of treatment across various tumor types, including combination immunotherapy, with the aim of providing patients with new therapeutic options. Meanwhile, we will continuously explore collaborations with the Chinese government, payers, and third-party organizations, and through innovative market access models and diversified initiatives, jointly enhance the accessibility of dual immunotherapy in China.”
It is reported that in October 2015, Opdivo in combination with Yervoy became the world's first regulatory authority-approved immunotherapyTumorCombination therapy has currently been approved for 6 tumor types in over 50 countries and regions worldwide, covering lung cancer, pleural mesothelioma,`Melanoma`, kidney cancer, colorectal cancer,Liver Cancer。