Medicine Y is here!

Recently, the world’s first CTLA-4 inhibitor Yiwo® (Ipilimumab, drug Y) was launched in China.
This is the first and only approved CTLA-4 inhibitor in China, which will inhibit PD-1.
Odivo® (Nivolumab, drug O) is used in combination with unresectable, newly-treated non-epithelioid malignant pleural mesothelioma (MPM) adult patients
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This is the first and only dual immunotherapy approved in China, marking the official opening of the era of dual immunotherapy in China
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In order to improve the availability of medications for patients, the China Cancer Foundation simultaneously launched a patient assistance program, adding indications for malignant pleural mesothelioma on the basis of the original Odivo patient assistance program, in order to reduce the economic burden of patients in treatment
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At present, Yiwo has officially landed in China and is available for purchase! This time, Cancer Degree invited the main researcher of CheckMate-743, Professor Lu Shun, director of the Department of Oncology, Shanghai Jiaotong University Thoracic Hospital, to be interviewed on the disease characteristics, prognosis and treatment status of pleural mesothelioma, as well as the dual immunotherapy.
In-depth communication was made for breakthrough significance
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1 The "breast" is successful: Survival benefits are long-lasting, and history is made.
Let us go back to June 11 this year.
The National Medical Products Administration (NMPA) officially approved Odivo® (Navulimab injection, Commonly known as O drug) combined with Yiwo® (Ipilimumab injection, commonly known as Y drug) is used for unresectable, newly treated adult patients with non-epithelioid malignant pleural mesothelioma
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This approval makes "Immune Gemini" 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! (Break: Immune Gemini has been approved for malignant pleural mesothelioma, filling the gap in the treatment of more than 15 years!) Malignant pleural mesothelioma is a rare, highly invasive and fatal malignant tumor that originates from the pleural mesothelium
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There are approximately 3,000 confirmed cases in China each year, accounting for one third of the new cases in Asia
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Asbestos is the main cause of malignant pleural mesothelioma
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As a major country in the production and use of asbestos, the incidence of malignant pleural mesothelioma in China is gradually increasing
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Professor Lu Shun, director of the Oncology Department of the Thoracic Hospital Affiliated to Shanghai Jiaotong University, said that the early symptoms of malignant pleural mesothelioma are not obvious, and most patients are in the advanced stage at the time of treatment
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Its clinical symptoms are mainly chest pain, and symptoms of chest tightness and shortness of breath will appear later
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Talking about the treatment of malignant pleural mesothelioma, Professor Lu Shun shared that the prognosis of malignant pleural mesothelioma is poor, and the median survival period of patients with advanced or metastatic malignant pleural mesothelioma that has not been treated in the past is 12 to 14 Between months, the five-year survival rate is about 10%
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Pemetrexed combined with platinum therapy is the traditional standard treatment.
In the past 15 years, no new systemic treatment plan that can effectively prolong the survival of patients has been approved in the world
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Until the CheckMate-743 clinical study appeared, it became the first and currently the only phase III clinical study to prove that first-line immunotherapy can improve the survival benefit of patients with unresectable malignant pleural mesothelioma compared with combined chemotherapy
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It is this study that provides reliable evidence-based medical evidence for the approval of dual immunotherapy for malignant pleural mesothelioma
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It is reported that the study enrolled a total of 605 patients with unresectable 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 at a ratio of 1:1.
In the chemotherapy group (302 cases) combined with platinum-based chemotherapy, the overall survival (OS) of all randomized patients was the primary research endpoint.
Other efficacy outcome indicators include progression-free survival (PFS), objective response rate (ORR) and sustained remission Time (DOR)
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O+Y double-immune overall survival sustained significant benefits Compared with the chemotherapy group, the O+Y double-immune treatment group reduced the risk of death by 27%; and regardless of histological type, overall survival was improved
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Data from the CheckMate-743 study showed that nearly a quarter of patients in the O+Y dual immunotherapy group survived for more than three years, with a median OS of 18.
1 months, and 14.
1 months in the chemotherapy group (hazard ratio [HR]: 0.
73), the risk of death decreased by 27%
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Figure 1.
Three-year OS follow-up data of the double-immune combination therapy group and the chemotherapy group in the CheckMate-743 study.
As the main researcher of CheckMate-743 in China, Professor Lu Shun pointed out that double-immune therapy has established a new standard of treatment
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According to the results of the CheckMate-743 study, the median survival time of patients in the dual-immune group reached 18.
1 months.
For advanced pleural mesothelioma, this median data is sufficient to change the standard treatment
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Nearly a quarter of patients survived for more than three years.
In the CheckMate-743 study, the 1-year and 2-year OS rates of patients receiving O+Y treatment were 68% and 41%, respectively, which were significantly higher than the 58% and 27% of the chemotherapy group Ratio
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At the time of follow-up to 3 years, the patient had stopped treatment for at least 1 year.
At this time, the 3-year OS rate of the patients receiving O+Y treatment was 23%, which was significantly higher than that of the chemotherapy group (15%), and the 3-year OS of the double-immune combination therapy group The rate is about 1.
5 times that of the chemotherapy group
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This means that among patients receiving dual immunotherapy, one in nearly four patients can live more than three years, while only 15% of the chemotherapy group survived more than three years
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O+Y first-line treatment can still continue to benefit patients with advanced MPM
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Moreover, it can be clearly seen from the survival curve that with the extension of follow-up time, the survival advantage of dual immune combination therapy becomes more obvious, and the long-term survival of patients is greatly improved
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Professor Lu Shun pointed out that the three-year follow-up results of the CheckMate-743 study showed that the three-year survival rate of patients in the dual-immunization group reached 23%, and 1/4 patients survived for more than three years, which can be said to further confirm the long-term survival of the dual-immunization group.
Benefit
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Patients in the dual immunotherapy group had longer disease remission.
The objective response rate (ORR) of patients in the dual immunotherapy group was comparable to that of the chemotherapy group; the median duration of remission (mDOR) of patients in the dual immunotherapy group was 11.
6 months, while that of the chemotherapy group was 6.
7 months
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The median duration of remission increased by 4.
9 months, reaching 1.
7 times that of chemotherapy, confirming that dual immunotherapy has a deeper and longer remission of the disease; nearly 30% (28%) of patients who respond to O+Y are after the start of the response3 Continued to respond throughout the year
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This part of the patients is very likely to get a longer survival time, more than 5 years, 10 years are possible
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In the chemotherapy group, the ratio was 0%
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Regardless of the histological type, dual immunotherapy can bring longer duration of remission for patients, indicating that the clinical application of O+Y combination has great universality
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Figure 2.
CheckMate-743 research on PFS and ORR/DOR has a unique data mechanism and good security.
Talking about the unique mechanism of the dual immune combination, Professor Lu Shun said that Odivo combined with Yiwo is a unique combination of two immune checkpoint inhibitors , Respectively target two different checkpoints (PD-1 and CTLA-4) to help kill tumor cells.
The two have a potential synergistic mechanism and can produce 1+1 >2 effects
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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 dual immunotherapy was consistent with the previously reported research results, and no new safety signals were observed
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The incidence of treatment-related adverse events (TRAEs) in the dual immunotherapy group was comparable to that in the chemotherapy group.
The overall incidence of TRAEs in the two groups was 80% and 82%, respectively, and the incidence of grade 3-4 TRAEs was 31% and 32%, respectively
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Post-mortem analysis found that the discontinuation of dual immunotherapy due to TRAEs did not have a negative impact on the long-term benefits of patients: among patients who discontinued the drug due to adverse reactions, the mOS was 25.
4 months, and the 3-year overall survival rate (OS) was 37%! On the whole, the side effects of dual immunotherapy are controllable
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Figure 3.
CheckMate743 study 3-year follow-up of patients who discontinued treatment due to TRAEs.
There are several "chest" data: patient assistance program launched, improving access to drugs In order to help more patients achieve high-quality long-term survival and improve the availability of innovative drugs In addition, the China Cancer Foundation has added a new indication for malignant pleural mesothelioma on the basis of the original "Odivo Patient Assistance Project"
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Patients who meet the project criteria can voluntarily submit an application for assistance in the treatment of "Odivo and Yiwo"
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According to the approved indications for malignant pleural mesothelioma, the Odivo Drug Assistance Program will provide differentiated assistance programs based on the dosage and medication cycle of Odivo
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1) Treat according to kilogram body weight (3mg/kg, once every 2 weeks), and the assistance plan is "3+3, 3+X"
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Patients who meet the criteria of the project are approved by the project office, and within an application year, after paying for 3 times, they can get 3 follow-up treatment medication assistance (3+3).
In the follow-up treatment, they can pay 3 times, that is Get all the drug assistance (3+X) remaining in the current year
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In short, if you pay yourself up to 6 times in an application year, you can get the remaining drug assistance in that year
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Patients can apply according to the annual application cycle until 24 months or the disease progresses
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2) According to the fixed dose (360mg, once every 3 weeks plan) treatment, the assistance plan is "2+2, 2+X"
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Patients who meet the criteria of the project are approved by the project office, and after paying twice within an application year, they can obtain assistance (2+2) for the subsequent 2 treatments.
In the follow-up treatment, they will pay 2 times, that is Get all the drug assistance (2+X) remaining in the current year
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In short, if you pay yourself up to 4 times in an application year, you can get the remaining drug assistance in that year
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Patients can apply according to the annual application cycle until 24 months or the disease progresses
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The Yiwo assistance program will adopt the "1+3" program, that is, patients who meet the project standards will be approved by the project office and paid once by themselves to receive up to 3 free drug assistance
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Patients can apply in cycles until 24 months or the disease progresses
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Taking a patient weighing 60 kg as an example, if the treatment is carried out by kg body weight, Odivo’s patient assistance part will adopt the "3+3, 3+X" model, while Yiwo’s assistance program is "1+3 "
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According to the O drug dosage of 3mg/kg, once every two weeks, the annual out-of-pocket cost of O drug for a 60kg patient is RMB 110,652 (6 times a year)
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The dosage and cycle of medicine Y is 1 mg/kg, once every six weeks
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The current market price of medicine Y: 50mg is 28,000 yuan
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The annual out-of-pocket cost of medicine Y for a 60kg patient is RMB 56,000 (two times a year)
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For patients who meet the aid criteria, the annual out-of-pocket cost of Odivo and Yiwo is expected to be reduced to 167,000 yuan, which is a 76% drop from the listed price.

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If the patient chooses a fixed-dose 360mg, once every 3 weeks O drug treatment plan combined with Y drug, after the patient assistance program, the annual cost savings are also 76%
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Patients who meet the project criteria can apply according to the requirements and procedures
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The application process and project materials for the new indications of the project will be announced on the official website of the China Cancer Foundation (http:// and the WeChat public account "China Cancer Foundation Odivo Project", or call the project Hotline 400-669-0906 for consultation
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3 "Chest" with great ambition: The first appearance of the edge, the future can be expected pleural mesothelioma is only the first show of Immune Gemini treatment 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! Talking about the application of dual immunity in other tumor types, Professor Lu Shun said that dual immunotherapy in Europe and the United States has been approved for lung cancer indications
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In China, the current research on dual immunity in lung cancer indications is also underway
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Looking to the future, this innovative solution that leads the transformation of tumor treatment models is expected to play a greater role in the treatment of more tumor types, providing a wide range of people with the possibility of "de-chemotherapy" and "less chemotherapy", and bringing more patients Treatment options
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Up to now, Bristol-Myers Squibb has carried out more than 30 immunological clinical studies in China, covering multiple high-incidence tumor types, including lung cancer, liver cancer, gastric cancer, esophageal cancer and urothelial cancer, to meet the most urgent treatment needs of patients
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It may still be a dream to cure cancer, but we are waiting for the day when the dream is reflected in reality.

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With the emergence of more innovative drugs like Yiwo, doctors have more advanced weapons, and patients have more hope of continuing their lives
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In this game with cancer, we are more likely to win than ever
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