CSCO Immuno-Oncology Summit Forum: Global Voices and Chinese Perspectives in the "Era of Maritime" Immunotherapy

In recent years, immuno-oncology (IO) has been in a stage of rapid development both globally and in China.

From 2018, the world's first PD-1 inhibitor nivolumab was first approved in China, to a total of 8 PD-1/PD-L1 inhibitors followed by listing in China; from the late cancer line The treatment started, and gradually advanced to the first-line and perioperative treatment; the medication regimen also changed from PD-1 single agent to combined chemotherapy and targeted therapy, and then combined with other immune checkpoint inhibitors, and the trend of innovation and development is in full swing.

In this context, in order to focus on immunotherapy innovation, the 2021 CSCO 4th National Tumor Immunotherapy Summit Forum will be officially held in Jinan on May 28-30.

Many Chinese experts gathered offline to discuss cutting-edge hotspots and share Chinese views, and overseas scientists also participated online to look forward to future trends and share global perspectives.

Global perspective: From PD-1, CTLA-4 to LAG-3, "immunity + immunity" opens the future.
As we all know, the medical oncology community is undergoing a transition from the era of traditional treatment to the era of immunotherapy.

Since the first immuno-oncology drug CTLA-4 inhibitor ipilimumab was approved in 2011, nearly 10 immunotherapeutic drugs have been marketed globally for the treatment of 15 tumor types.

In 2019, a total of 2,975 immunotherapy clinical studies are underway globally.

These data show that the rapid development of immunotherapy is changing the practice of tumor treatment in all aspects.

At the "Comprehensive Forum on Immunotherapy", Joseph Eid, Senior Vice President of Global Medical Affairs of Bristol-Myers Squibb, gave an online keynote speech and looked forward to the new global development trend of immuno-oncology therapy.

Following immune monotherapy, immune + chemotherapy or targeted therapy, immune + immune (such as PD-1+CTLA-4 or PD-1+LAG-3) is becoming an important strategy and future direction of immune frontier exploration.

Joseph Eid mentioned in his speech that the first phase III clinical study of LAG-3 inhibitor, a new target for immunotherapy, RELATIVITY-047, has recently announced the results.

The LAG-3 inhibitor Relatlimab combined with the PD-1 inhibitor nivolumab as the first-line treatment of advanced melanoma, compared with the nivolumab monotherapy group, the median PFS of patients doubled.

LAG-3 is the third immune checkpoint target to enter clinical trials after CTLA-4 and PD-1.
It plays an important role in the regulation of T cell activation, proliferation and homeostasis.

The success of RELATIVITY-047 not only clarified the clinical value of LAG-3 inhibitors for the first time, but also confirmed its synergistic effect with PD-1 inhibitors, undoubtedly injecting another inotropic agent into the academic and research and development of immunotherapy.

Through the global perspective shared by Joseph E.
Eid, it can be foreseen that, on the one hand, traditional treatment methods such as immunotherapy monotherapy or combined chemotherapy are fully integrated into clinical practice and are in the ascendant; on the other hand, "immunization + immunity" is gradually entering the market.
The center of the stage: As PD-L1 inhibitors combined with CTLA-4 or LAG-3 inhibitors have made important breakthroughs in phase III clinical studies, the future of immunotherapy and tumor treatment will also usher in more development opportunities .

China's view: Immunization exploration is progressing in multiple lines, starting from the back line to the first line, and perioperative treatment is advancing the global exploration of immunotherapy.
It also provides a lot of experience and inspiration for clinical diagnosis and treatment in China.

In each link of this conference, many domestic authoritative experts based on China's practice, interpreted the important phase III clinical research results of immunotherapy and their significance in recent years.

The first-line blockbuster advanced or metastatic cancer is the starting point of immunotherapy exploration.

Due to the rapid progress of advanced cancer, first-line treatment is often the best opportunity for patients to obtain curative effects.
Therefore, the research results of first-line treatment have always attracted attention.

First-line gastric immunity, China refreshes history.
Gastric cancer is the second most common type of cancer with Chinese "characteristics", but the research progress of its first-line treatment has been stagnated for a long time.

Even in the age of immunotherapy, many clinical studies based on PD-1/PD-L1 have returned.

In this context, the CheckMate-649 study has achieved a landmark "double superiority" result.
It is the world's first and so far only phase III clinical study with positive results for the first-line immunotherapy of gastric cancer.

Nivolumab combined with chemotherapy is used in the first-line treatment of advanced or metastatic gastric cancer.
In people with CPS ≥ 5, overall survival (OS)/progression-free survival (PFS) is significantly better than chemotherapy alone (OS: 14.
4) Month vs 11.
1 months, P<0.
0001; PFS: 7.
7 months vs 6.
0 months, P<0.
0001); in the population with CPS≥1 and all randomized patients, statistically significant OS benefits were also observed.

Not only that, the results of the CheckMate-649 study in the Chinese subgroup published in April this year further show that the benefits of Chinese patients are consistent with the overall population, and the OS benefit can reach nearly 6 months (15.
5 months vs 9.
6 months).
Chinese patients with advanced gastric cancer have brought the best survival benefit so far in the phase III clinical study.

Based on the results of CheckMate-649, the indication for this regimen for the first-line treatment of advanced gastric cancer has been approved by the FDA, and regardless of the expression levels of HER2 and PD-L1, it has become the world's first approved first-line immunotherapy drug for gastric cancer.

Professor Zhang Xiaotian from Peking University Cancer Hospital interpreted the CheckMate-649 research in the "Progress in Gastric Cancer Immunotherapy" section of this conference and gave it a high evaluation: Professor Zhang Xiaotian has been slow in the first-line treatment of advanced gastric cancer for a long time.
, Anti-HER2 targeted therapy can only cover about 12-13% of patients, and the remaining patients can only rely on chemotherapy.

The results of the exploration of immunotherapy in gastric cancer were initially frustrating.
It was not until the results of CheckMate-649 was announced that it ended doubts and controversies about the value of immunotherapy for gastric cancer and opened up the dilemma that only chemotherapy is available for the first-line treatment of HER2-negative gastric cancer A brand new road.

Data from the Chinese subgroup of CheckMate-649 further show that Chinese patients have achieved better results than the global population, indicating that first-line immunotherapy is likely to be more in line with China's gastric cancer treatment practice.
This program is expected to set a new standard for first-line treatment of advanced gastric cancer in China .

First-line double immunity, lung cancer bears the brunt of the first-line treatment of non-small cell lung cancer (NSCLC) has always been an important position for immune exploration, but there are still some unmet needs.

For example, the first-line immunization single-drug regimen can only cover NSCLC patients with PD-L1 ≥ 1%, and immunization + chemotherapy expands the beneficiary population, but neither can completely replace chemotherapy.

Then, through the dual immunotherapy of PD-1+CTLA-4, can a broad-spectrum use of patients who do not rely on chemotherapy be achieved, triggering the opening of the era of "de-chemotherapy" first-line lung cancer treatment? According to the three-year follow-up results of the CheckMate-227 study, compared with chemotherapy, the PD-1 inhibitor nivolumab combined with the CTLA-4 inhibitor ipilimumab (O+Y) treatment improved the OS of the Asian population.
Consistent with the benefits of the global population, even better numerically.

In patients with PD-L1≥1% and <1%, O+Y reduced the risk of death by 28% and 34%, respectively.

The OS rate of Asian populations receiving dual immunotherapy is more than 10% higher than that of the global population.
At the same time, as time goes by, the trend of OS for Asian populations is more obvious.

In addition, in order to effectively control the risk of early disease progression in immunotherapy and weaken the problem of slow immune onset, another CheckMate -9LA study pioneered the addition of two cycles of chemotherapy (O+Y+ two-cycle chemotherapy) to the dual-immune combination.

According to data with a median follow-up of 13.
2 months, triple therapy compared with chemotherapy alone can bring significant OS and PFS benefits (OS: 15.
6 months vs 10.
9 months; 1-year PFS rate: 33% vs 18%), and the same Not limited by the expression level of PD-L1.

Professor Wang Jun from the First Affiliated Hospital of Shandong First Medical University commented on the results of these two important studies and their significance in the "Research Progress in Advanced Thoracic Tumor Combination Therapy" session of the conference satellite conference: Professor Wang Jun's drive For patients with gene-negative advanced NSCLC, the existing first-line immune monotherapy requires precise screening of patients, and achieving "chemotherapy-free" for a wider population is always the direction of our clinical efforts.

The exploration results of dual immune combination therapy represented by CheckMate -227 and CheckMate -9LA provide us with a "no chemotherapy" and "less chemotherapy" program that can bring long-term survival, benefit a wide range of people, and is well tolerated .

Whether it is "O+Y" or "O+Y+chemotherapy", these two programs provide patients with new first-line treatment options to avoid long-term chemotherapy, which is a big step toward the goal of "going to chemotherapy".

Pleural mesothelioma, a 15-year dilemma, including the above-mentioned NSCLC, the "O+Y" dual immune combination has been proven to bring significant survival benefits in the treatment of 7 cancer types.
Its latest achievement The clinical breakthrough is for the first-line treatment of rare malignant pleural mesothelioma.

As a rare but extremely malignant tumor, its treatment progress is very slow, and it has not ushered in a breakthrough for nearly 15 years.

The CheckMate -743 study explored the efficacy of the "O+Y" non-chemotherapy combination versus standard chemotherapy for the first-line treatment of malignant pleural mesothelioma.

The results show that O+Y can greatly improve the prognosis of patients.
The 2-year OS rate reaches 41%, which is 1.
5 times that of chemotherapy (27%).
Once it is effective, the median remission time is nearly twice that of chemotherapy (11.
0 months vs.
6.
7 months), the 2-year continuous remission rate can be 4 times that of chemotherapy (32% vs 8%).

Also in the conference "Research Progress in Dual Immunotherapy for Advanced Thoracic Tumors", Professor Wang Jun also interpreted the CheckMate-743 research results of O+Y combined treatment of malignant pleural mesothelioma.

Professor Wang Jun’s previous treatment for malignant pleural mesothelioma has an unsatisfactory prognosis.
Since the current standard chemotherapy regimen was approved in 2004, no new systemic therapy has been approved for more than 15 years.

The CheckMate-743 study achieved the first success of immunotherapy in the treatment of this rare tumor, and once again confirmed the advantages of immunotherapy "pan-tumor species".

From the data point of view, the OS and DoR curves of the O+Y group both show the "long tail effect" of long-term benefits once immunotherapy takes effect; it is expected that this dual-immune combination therapy can bring benefits to patients suffering from this rare tumor.
New hope for survival.

Assisting Youdao Based on the front-line treatment of advanced cancer, immunotherapy continues to advance to the frontline.

At present, the use of immunotherapy for the perioperative treatment of operable cancer has become a hot spot for exploration.
Phase III research results cover a number of different cancer types, including adjuvant and neoadjuvant, immune monotherapy and combination therapy, filling the various treatments.
There are many gaps in the field.

The "new" auxiliary approach to lung cancer neoadjuvant treatment of lung cancer has long been dominated by chemotherapy before surgery, and the median pathological complete remission (pCR) rate after surgery is only about 4%.

Immunotherapy for neoadjuvant treatment of resectable NSCLC has previously shown potential in multiple phase I/II clinical studies.

Subsequently, the Phase III clinical study CheckMate-816 announced the first round of positive results recently.

The data shows that 24% of the people who received immunization + chemotherapy intention-to-treat (ITT) achieved pCR, which was more than 10 times that of chemotherapy alone (2.
2%); among the population who received immunization + chemotherapy and surgical resection, the pCR rate was as high as nearly 1 /3 (30.
5%), and it is also nearly 10 times that of chemotherapy (3.
2%).

With this result, nivolumab becomes the first immunotherapy that has been confirmed by a phase III study for neoadjuvant therapy and can bring significant benefits to NSCLC patients.

Professor Hu Jian from the First Affiliated Hospital of Zhejiang University commented at the conference "Advances in Early Non-Small Cell Lung Cancer Immunotherapy": Professor Hu Jian in clinical practice, even if he undergoes radical surgery, there are still quite a few NSCLC patients.
Recurrence and metastasis.

Existing neoadjuvant chemotherapy can only bring about a 5% increase in the 5-year OS rate, and there is an urgent need for better neoadjuvant treatments in clinical practice.

The positive result of CheckMate -816 clarified the value of immunotherapy in the neoadjuvant treatment of NSCLC for the first time, which is a milestone.

From the data point of view, the addition of immunotherapy on the basis of chemotherapy has brought a nearly 10-fold increase in the pCR rate, suggesting that immunotherapy + chemotherapy for neoadjuvant therapy can bring significant pathological relief.

The immune + chemotherapy model led by CheckMate -816 is expected to change the current pattern of chemotherapy-led neoadjuvant therapy for NSCLC as a whole.

In the field of esophageal cancer, the current standard treatment for patients with resectable locally advanced esophageal cancer/gastroesophageal junction cancer (EC/GEJC) is the triple mode of neoadjuvant concurrent chemoradiotherapy (CRT) sequential surgery.
However, patients still have a higher risk of recurrence after treatment, especially those with residual disease.

Fortunately, the first immunoadjuvant treatment for esophageal cancer, nivolumab, has been approved in the United States recently.

According to CheckMate-577, which is approved based on the approval, the median disease-free survival (DFS) of patients who received neoadjuvant CRT and complete surgical resection still has residual pathology after adjuvant treatment with nivolumab can reach 22.
4 months , Which is more than twice the placebo (11.
0 months), and both squamous cell carcinoma and adenocarcinoma can benefit.

In the "Esophageal Cancer Perioperative Immunotherapy" session of the conference satellite conference, Professor Hu Jian further explained: Professor Hu Jian has about 70-75% of patients with early or late stage EC/GEJC undergoing CRT sequential surgery.
Unable to achieve complete pathological remission.

These patients have a higher risk of recurrence and metastasis, but there is currently no standard adjuvant treatment.

CheckMate -577 is the first phase III adjuvant immunotherapy study in the world for patients with EC/GEJC who have pathological residual after receiving neoadjuvant therapy.
It is not only another result of the advancement of immunotherapy to the perioperative period, but also It also fills the gap in this treatment field.

The recent approval of this indication also provides these patients with an important treatment option that can reduce the risk of recurrence.

In the "Urinary System Tumor Immunotherapy Development" section of the conference, Professor Ye Dingwei from Fudan University Cancer Hospital introduced the exploration of immunotherapy in this field.

Among them, the CheckMate-274 study in the field of postoperative adjuvant treatment of bladder cancer is the world's first and currently the only phase III study to prove that immunotherapy is used in patients with muscular invasive urothelial carcinoma after surgery, which can bring significant benefits.
The end point is DFS.

The first round of results announced by it showed that among the ITT population, the median DFS of patients treated with nivolumab was 21.
0 months, which was more than twice that of placebo (10.
9 months), and it could reduce disease recurrence by 30%.
risk.

PD-L1 positive patients benefit more obviously.

Regarding this result, Professor Ye Dingwei from Fudan University Cancer Hospital commented: Professor Ye Dingwei’s primary invasive urothelial carcinoma is one of the main pathological types of bladder cancer, which is characterized by a high probability of postoperative recurrence and metastasis, up to 50%.
%about.

For patients with a high risk of recurrence, the current standard regimen is postoperative platinum-containing adjuvant chemotherapy, but some patients have poor liver and kidney function, resulting in poor tolerance and unsatisfactory prognosis.
There is an urgent need for innovative treatment methods.

CheckMate-274 is currently the only clinical research that has confirmed the value of immunotherapy in the adjuvant treatment of bladder cancer, providing an important treatment option for clinical practice.

Based in China and looking at the world, the CSCO Immuno-oncology Summit Forum provides an opportunity to fully understand the current development pattern of immunotherapy.

The chairman of this conference, Professor Wang Baocheng of the 960th Hospital of the People's Liberation Army concluded: Professor Wang Baocheng's rapid development of immunotherapy has brought tumor treatment into a whole new stage.

From new immunotherapy targets, new immune combination programs, to wider application of cancer types, and more front-line application opportunities, immunotherapy is advancing simultaneously in the two dimensions of "depth" and "breadth".

With the continuous deepening of frontier exploration and the continuous accumulation of application experience, it is believed that in the near future, the survival of cancer patients is expected to achieve a major leap.