Breaking the game: Immune Gemini was approved for malignant pleural mesothelioma, filling the gap in treatment for more than 15 years!

2021 is the third year that immunotherapy has been registered in China.
In just three years, immune checkpoint inhibitors with PD-1/PD-L1 as the core have reshaped the pattern of cancer treatment in China, following chemotherapy and targeting After the treatment, the era of tumor immunotherapy began
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In just these two days, another breakthrough in immunotherapy: The National Medical Products Administration (NMPA) officially approved Odivo® (Navulimab injection, commonly known as O drug) combined with Yiwo® (Ipilimumab injection) Liquid, commonly known as Y drug) is used for non-epithelioid malignant pleural mesothelioma in adult patients who are unresectable and newly treated
.

"Immune Gemini" (Odivo® combined with Yiwo®) has become the first new systemic therapy that brings survival benefits to patients with malignant pleural mesothelioma in 15 years, and the era of dual immunotherapy in China has officially opened! As the pioneer of tumor immunotherapy, ipilimumab (Drug Y) is the first immune checkpoint inhibitor approved for marketing in the world, and this approval has also made ipilimumab become China’s The first and currently the only approved CTLA-4 inhibitor
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Poor "chest" is extremely evil, and the five-year survival rate is less than 10%.
Pleural mesothelioma is a primary tumor derived from pleural mesothelial cells with a low incidence rate and is a rare type of tumor
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Pleural mesothelioma is mainly divided into two subtypes, one is epithelial and the other is non-epithelial
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Long-term exposure to asbestos is a high-risk factor for pleural mesothelioma [1].
When asbestos fine fibers are inhaled into the lungs, it causes cell damage and chronic inflammation.
As asbestos is very stable, it will increase year after year.
Risk of cancer
.

Moreover, the incubation period from asbestos exposure to occurrence of mesothelioma is very long, which can be as long as 20-50 years [2]
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Other pathogenic factors of pleural mesothelioma include hereditary BAP1 gene mutations and previous radiotherapy [1]
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When people with this mutation are unfortunately exposed to asbestos, the combined effects of internal and external causes greatly increase the risk of pleural mesothelioma
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About 3000 people are diagnosed with mesothelioma every year in China [3]
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Early symptoms of malignant pleural mesothelioma are not obvious, and patients with advanced stages will have severe chest pain or dyspnea.
The vast majority of patients are already in the advanced stage at the time of diagnosis, and the treatment effect is greatly reduced
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In the past 15 years or so, the research of new drugs for malignant pleural mesothelioma has been slow, and has been stagnated in the traditional treatment model based on chemotherapy for a long time, and the treatment effect has not been good
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The median survival time of advanced patients is less than one year, and the five-year survival rate is less than 10% [4]
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In particular, patients with advanced non-epithelial subtypes have a shorter survival period.
New drugs are urgently needed to improve the treatment status of malignant pleural mesothelioma and prolong the survival time of patients
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 "Chest" has success: gnaw on the'hardest' bones to immune Gemini and win the battle! Fortunately, the emergence of tumor immunotherapy in recent years has brought new hope to patients! Research on immunotherapy for malignant pleural mesothelioma is in full swing
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Among them, the leader is the combination therapy of Immune Gemini (Odivo® combined with Yiwo®)
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This approval is based on a clinical study called CheckMate-743, which is the first and currently the only randomized, phase III clinical trial to prove that first-line dual immunotherapy versus chemotherapy can bring survival benefits to all patients with malignant pleural mesothelioma Research
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The study enrolled a total of 605 patients with advanced malignant pleural mesothelioma who had not been treated before, and they were randomly assigned to the Odivo® combined with Evo® group (303 cases) or pemetrexed combined with platinum at a ratio of 1:1 In the chemotherapy group (302 cases), the overall survival (OS) of all randomized patients was the main research endpoint, and other efficacy outcome indicators included progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR)
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And according to the different pathological types of epithelioid and non-epithelial for subgroup analysis
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The results live up to expectations! At the shortest follow-up of 22 months, the median OS of the dual immunotherapy group was 18.
1 months and that of the chemotherapy group was 14.
1 months (hazard ratio [HR]: 0.
74 [96.
6% confidence interval]: 0.
60, 0.
91; p=0.
002 ), the risk of death is reduced by 26%, which is significantly higher than the median survival of only one year in the past! Compared with chemotherapy alone, more than 40% of patients are still alive after 2 years of dual immunotherapy (the 2-year OS rate is 41% vs 27%)
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The results of the subgroups that continue to be analyzed in depth are even more amazing
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Among non-epithelioid patients with poor prognosis, the median overall survival of patients in the dual immunotherapy group reached 18.
1 months, more than twice that of the chemotherapy group (8.
8 months in the chemotherapy group), and the risk of death was reduced by 54%, 2 years The survival rate is 38%! You know, in the clinical research of advanced pleural mesothelioma, the survival period is extended by 2 months is already very good, and the extension of nearly 10 months is a huge leap
.

The effect of the non-epithelial type is so good, how about the effect of the epithelial type? The answer is equally good! Among patients with epithelioid type, the median OS of the dual immunotherapy group and the chemotherapy group were 18.
7 months and 16.
5 months, respectively, and the survival time was definitely improved
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In other words, no matter which type of patient, the survival period of dual immunotherapy is prolonged
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Based on the excellent results of the CheckMate-743 study and the highly unmet clinical need for treatment, NMPA officially approved Odivo combined with Yiwo as the first-line treatment for patients with advanced non-epithelial malignant pleural mesothelioma
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In the newly released "Chinese Society of Clinical Oncology (CSCO) Guidelines for the Clinical Application of Immune Checkpoint Inhibitors (2021 Edition)" [6], the treatment of malignant pleural mesothelioma was included for the first time.
Immune Gemini (Odivo ® combined with Yiwo ®) first-line treatment of non-epitheloid and epithelioid pleural mesothelioma has become the only treatment plan that has obtained Class I (Class 1 evidence) and Class II recommendations (Class 2A evidence)
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Professor Lu Shun, chief investigator of CheckMate-743 and director of the Department of Oncology, Shanghai Jiaotong University Thoracic Hospital, said: "Malignant pleural mesothelioma is a highly aggressive and rare cancer with limited treatment options
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Its incidence is related to asbestos exposure.
Highly correlated, most patients are already at an advanced stage at the time of diagnosis, and the 5-year survival rate is less than 10% [5]
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Among all histological types, patients with non-epithelial tissue types have a worse prognosis [2], and patients urgently need new The treatment plan to improve the treatment effect and prolong survival time
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As the first approved systemic therapy in 15 years, Odiwo combined with Yiwo brings twice the overall survival benefit of chemotherapy for non-epithelial patients, making patients Long-term survival is possible and has a milestone significance.
It is expected to become the new standard treatment for malignant pleural mesothelioma
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"The overall situation is in the "chest": a unique mechanism of action to ensure efficacy, and safety and immunity Gemini (Odivo® combined with Yiwo®) It is a unique combination of two immune checkpoint inhibitors, which target two different checkpoints (PD-1 and CTLA-4) to help destroy tumor cells.
The two have a potential synergistic mechanism: Yiwo can promote T Cell activation and proliferation, and Odivo helps existing T cells recognize tumor cells
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Some T cells activated by Yiwo can also differentiate into memory T cells, helping to achieve long-term anti-tumor immune response
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Just like the Heavenly Sword and the Dragon Sword, the combination of the two swords inspires super combat power, and the joint pursuit and killing makes the tumor cells invisible
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While ensuring the efficacy, safety has also been taken into account
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In the CheckMate-743 study, the safety of Odivo and Yiwo was consistent with the results of previous reports, and no new safety signals were observed
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The treatment-related adverse events (TRAE) of any level in the dual immunotherapy group and the chemotherapy group were similar, with the incidence of 80% and 82%, respectively
.

Grade 3-4 adverse events were 30.
3% in the dual immunotherapy group and 32.
0% in the chemotherapy group
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The safety of the dual immunization regimen is equivalent to that of chemotherapy, and the patient is well tolerated! 'Chest' with great ambitions: Dual immunotherapy is beginning to show its edge, and the future is expected to be the life director of Guangdong Provincial People’s Hospital and the honorary director of Guangdong Lung Cancer Institute (GLCI) Professor Wu Yilong said: “Odivo and Yiwo are able to reach the advanced stage through potential synergistic effects.
Patients with malignant pleural mesothelioma bring significant and long-lasting overall survival benefits, making it possible to "de-chemotherapy"
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In the CheckMate-743 study, Odivo (3mg/kg, once every 2 weeks) combined with Yiwo (1mg /kg, once every 6 weeks) The safety characteristics of the first-line treatment of malignant pleural mesothelioma are consistent with the safety of the combination therapy in previous studies of other tumor types, including the first-line dual immunotherapy for lung cancer, which achieves efficacy and safety Balance indicates that the dual immune combination therapy will have the opportunity to benefit Chinese patients in different tumor types in the future
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"Pleural mesothelioma is just the first show of immunogemini therapy in China
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Since Odivo and Yiwo became the world's first immuno-oncology combination therapy approved by regulatory agencies in October 2015, 6 tumor types have been approved in more than 50 countries and regions around the world, covering lung cancer and pleural mesothelioma , Melanoma, kidney cancer, colorectal cancer, liver cancer
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The approval of China's "Immune Gemini" will also fully trigger the rise of China's dual immunity! It is reported that at the just-concluded 2021 ASCO annual meeting, Immune Gemini-based combination therapy updated the follow-up data of two important first-line dual immunotherapy studies of lung cancer, CheckMate-9LA and CheckMate-227
.

The 2-year follow-up data of the CheckMate-9LA study showed that compared with the chemotherapy alone group, the survival time of patients receiving dual-immunization combined with a limited course of chemotherapy was significantly prolonged (15.
8 months vs.
11.
0 months), and patients in the two groups who lived for 2 years accounted for the total population The ratios were 38% vs 26%
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The data of the CheckMate-227 study for 4 years showed that among patients with PD-L1 ≥ 1%, 29% of patients who received dual immunotherapy survived 4 years, and 18% in the single-agent chemotherapy group
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Among patients with PD-L1≥50%, this data was 37% vs 20%, respectively
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In patients with PD-L1<1%, this data was 24% vs 10%, respectively
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The updated data of the two studies coincidentally once again confirmed the long-term survival benefits of dual immunization for lung cancer patients
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Dual immunotherapy is emerging.
Looking forward to the future, this innovative solution that leads the transformation of tumor treatment models is expected to be approved for more tumor types such as lung cancer, providing a wide range of people with the possibility of "removing chemotherapy" and "less chemotherapy", and bringing patients More treatment options
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 References [1] Daniel H Sterman, et al.
Epidemiology of malignant pleural mesothelioma.
UpToDate.
[2] Daniel H Sterman, et al.
Manifestations, initial evaluation and prognosis of malignant pleural mesothelioma UpToDate[3] https://gco.
iarc.
fr/today/data/factsheets/populations/160-china-fact-sheets.
pdf.
[4]Tang Shanwei, et al.
Research progress in the treatment of malignant pleural mesothelioma.
Cancer progress.
2019, 17(11): 1245-1250.
[5] American Cancer Society 2010-2016.
[6] Chinese Society of Clinical Oncology Guidelines Working Committee.
Chinese Society of Clinical Oncology (CSCO) Immune Checkpoint Inhibitors Clinical Application Guidelines (2021 Edition).
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