"The King of Stomach" Continues to Write a Chinese Chapter, Looking Forward to the Data of CheckMate -649 Chinese Subgroup

Preface In 2020, the large-scale phase III clinical study CheckMate-649 of nivolumab (Odivo, drug O) combined with chemotherapy for the first-line treatment of advanced gastric cancer, gastroesophageal junction cancer and esophageal adenocarcinoma was a great success.

The first round of detailed data showed that: nivolumab combined with chemotherapy for the first-line treatment of advanced gastric cancer, in patients with a combined positive score (CPS) ≥5, the overall survival (OS) is 14.
4 months, and the progression-free survival ( PFS) up to 7.
7 months, which was significantly better than chemotherapy alone (11.
1 months, 6.
0 months); at the same time, OS benefit was also observed in patients with CPS ≥ 1 and all randomized patients.

In the field of first-line treatment of advanced gastric cancer, this is also the first and only PD-1 inhibitor combination chemotherapy.
Both OS and PFS are better than the results of the phase III study of chemotherapy alone.

According to the latest agenda of the American Association for Cancer Research (AACR) in 2021, the largest randomized controlled, global phase III clinical study CheckMate-649 study in the field of gastric cancer and esophageal adenocarcinoma has so far carried out the Chinese subgroup data of the CheckMate-649 study.
Heavy release on Saturday.

As the detailed data is about to be announced, more than 20 Chinese researchers who participated in the CheckMate-649 study will bring you their insights and highlights in advance: China is a major gastric cancer country.

According to data from the Global Cancer Observatory in 2020, the number of new cases of gastric cancer in China is 478,000, and the number of deaths is 374,0001, accounting for 44% and 49% of the global number of new cases and deaths2; and 80% of the cases Chinese gastric cancer patients have reached the advanced stage when they are diagnosed, and they have lost the opportunity for radical surgery.

Since many patients with advanced or metastatic gastric cancer cannot tolerate subsequent treatment due to their worsening condition, first-line treatment is a key factor in determining the survival benefit of patients and the effect of subsequent treatment.

However, in the past ten years, with the exception of HER2 targeted drugs, the first-line drug treatment of advanced gastric cancer has not made progress.

And in China, HER2-positive patients account for only 12%-13%.

Therefore, chemotherapy is still the standard first-line treatment for most patients, and usually only brings survival benefits of less than one year.

In 2020, the release of the overall data of the CheckMate-649 study not only gave doctors and patients confidence in the first-line treatment of gastric cancer, but also ended the long-standing controversy over immunotherapy for gastric cancer.

However, due to the high heterogeneity of gastric cancer, there are big differences in the onset characteristics, biological behaviors, and treatment modes of the eastern and western populations.
The efficacy and safety of nivolumab combined with chemotherapy in Chinese patients are still unknown.
.

In response to this problem, in terms of research design, the CheckMate-649 study included test centers almost all over the world.
The large sample size included various gastric cancer types from the East and the West, evenly covering the molecular types required for the study, and gastric cancer was considered.
The highly heterogeneous problem of treatment.

In addition, among the gastric cancer immunotherapy studies with published data results, CheckMate-649 is the first global multicenter phase III study to include the mainland Chinese population.
The number of Chinese patients accounted for the highest proportion of the enrolled Asian patients, reaching 60%.

Through the research design, it can be found that the strategy of the combined plan is highly consistent with the current clinical practice in China.
The stratification factors take into account the clinically relevant prognostic factors.
The characteristics of the patients included in the group are representative of first-line gastric cancer disease, and the baseline clinical characteristics are balanced.
These are important for China.
The population's benefit and risk assessment provides a sound basis.

However, in the end, data must be used to speak.

Can CheckMate-649 Chinese subgroup data bring opportunities and changes to the treatment of gastric cancer in China? Please lock in on April 10th at 20:30, Beijing time, 2021 AACR Conference on CheckMate-649 Study CheckMate-649 is a phase III randomized, multi-center, open-label clinical study designed to evaluate Navulio compared with chemotherapy alone The efficacy of monoclonal antibody combined with chemotherapy or nivolumab combined with ipilimumab for the treatment of patients with HER2-negative, advanced or metastatic gastric cancer, gastroesophageal junction cancer or esophageal adenocarcinoma who have not received previous treatment.

The primary endpoint of the study was compared with chemotherapy alone, nivouximab combined with chemotherapy for OS in patients with positive PD-L1 expression, ie CPS ≥ 5, and PFS based on a blinded independent central review committee (BICR) assessment.

Key secondary endpoints include the OS of patients with CPS ≥ 1 and all randomized patients who received nivolumumab combined with chemotherapy, and the OS of patients who received nivolumab combined with ipilimumab versus chemotherapy alone and the time to symptom worsening (TTSD).

 Patients in the nivolumab combined with chemotherapy group received nivolumab 360 mg combined with capecitabine and oxaliplatin (CapeOX) every 3 weeks; or received nivolumab 240 mg combined with 5- Treatment with fluorouracil, leucovorin and oxaliplatin (FOLFOX) every 2 weeks.

Patients in the nivolumumab combined with ipilimumab group received nivolumab 1 mg/kg combined with ipilimumab 3 mg/kg, once every 3 weeks, after four consecutive cycles of administration, sequential administration Wuliyuumab 240 mg, once every 2 weeks.

Patients in the chemotherapy group received FOLFOX treatment, once every 2 weeks, or CapeOX treatment, once every 3 weeks.

All patients continued treatment for up to two years, or until disease progression, intolerable toxicity, or withdrawal of informed consent.

References: 1.
WHO, Globocan 2020 Stomach.
https://gco.
iarc.
fr/today/data/factsheets/cancers/7-Stomach-fact-sheet.
pdf 2.
WHO, Globocan 2020 China.
http://gco .
iarc.
fr/today/data/factsheets/populations/160-china-fact-sheets.
pdf