On March 3, 2022, local time, cancer cell (impact factor: 31.743), a top international oncology journal, published the results of a large-scale prospective phase III clinical study (JUPITER-06 study) independently developed by the mainland on PD-1 immunotherapy drug Treprimumab combined with chemotherapy for the first-line treatment of advanced or metastatic esophageal squamous cell carcinoma, with Professor Xu Ruihua and Professor Wang Feng of the Cancer Prevention and Control Center of Sun Yat-sen University as co-corresponding authors.
Screenshot of the Cancer Cell web page
The JUPITER-06 study was led by Professor Xu Ruihua and Professor Wang Feng, and was jointly carried out by 72 units across the country, including the Cancer Prevention and Control Center of Sun Yat-sen University, the Cancer Hospital of the Chinese Academy of Medical Sciences, the First Affiliated Hospital of Henan University of Science and Technology, and the Affiliated Cancer Hospital of Harbin Medical University. The results of the study showed that treprizumab combined with TP chemotherapy (paclitaxel + cisplatin) significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced esophageal squamous cell carcinoma compared with chemotherapy alone, with median OS significantly extended by 55% to 17 months, setting a new survival record for first-line treatment for advanced esophageal squamous cell carcinoma.
This is a major contribution of Chinese scholars to the field of international immunotherapy with Chinese original research drugs, which is expected to completely change the treatment pattern of advanced esophageal squamous cell carcinoma and establish a new first-line treatment standard.
Professor Xu Ruihua said that the JUPITER-06 study focused on the population with high incidence of esophageal squamous cell carcinoma in China, and applied the immunotherapy preparations of domestic original research, which is conducive to solving the gap in the treatment needs of mainland patients and meeting the major strategic needs of the country. It is expected that treprizumab combined with TP chemotherapy will become a new standard for the first-line treatment of advanced esophageal squamous cell carcinoma, bringing better treatment options for patients with esophageal squamous cell carcinoma in China and even the world.
Professor Ruihua Xu, the principal investigator of JUPITER-06
Cancer Cell also published an accompanying editorial from Dr. Ken Kato of the National Cancer Research Center Central Hospital of Japan as a corresponding author, mentioning, "Jupiter-06 studies have shown that compared with chemotherapy alone, triprimumab combined chemotherapy has brought superior progression-free survival (PFS) and overall survival (OS) for patients with advanced esophageal squamous cell carcinoma who have not been treated before, This provides conclusive evidence that immune checkpoint inhibitors are the key drugs for the first-line treatment of advanced esophageal squamous cell carcinoma. ”
Esophageal cancer is one of the most common malignancies in the gastrointestinal tract. According to statistics, in 2020, the number of new cases of esophageal cancer in China reached 320,000, and the number of deaths also reached 300,000, which exceeded more than half of the world's total, and the morbidity and mortality rate ranked fifth and fourth among all malignant tumors, respectively. Esophageal squamous cell carcinoma and adenocarcinoma are the two main histological subtypes of esophageal cancer, and patients in Europe and the United States are mostly esophageal adenocarcinoma, Asian patients with esophageal squamous cell carcinoma (ESCC) as the main subtype, accounting for more than 90% of the total number of cases.
Although surgery is the best option for radical treatment with non-metastatic ESCC, postoperative recurrences often occur. In addition, because the early symptoms of esophageal cancer are not obvious, most patients are already advanced at the time of initial diagnosis. For patients with advanced or metastatic ESCC, the current first-line standard therapy mostly uses platinum-containing dual-agent chemotherapy regimens, but the clinical benefit is limited, the median survival is only about 1 year, the 5-year survival rate is less than 20%, and new drugs and treatment options are urgently needed to prolong the survival of patients.
The emergence of tumor immunotherapy, represented by PD-1 inhibitors, has brought a huge turnaround for the survival of patients with advanced esophageal cancer. International exploration of immunotherapy for advanced esophageal cancer started early, but due to the different pathogenesis and pathological characteristics of patients in the East and the West, clinical evidence for ESCC, the main subtype of esophageal cancer in mainland China, is still lacking.
JUPITER-06 Research Center and enterprise representatives participated in the data release ceremony
Triprimumab is the first domestic PD-1-target monoclonal antibody drug approved for marketing in mainland China, independently developed by the local innovative pharmaceutical company Junshi Biotech for the treatment of a variety of malignant tumors. In 2017, Professor Xu Ruihua's team carried out a number of early exploratory studies on the treatment of different malignant tumors with triprimumab monotherapy or combined chemotherapy regimens, and achieved positive results in the field of ESCC treatment, providing a solid theoretical foundation for subsequent large-scale phase III studies. Combining a large amount of clinical practice experience and basic scientific research, the research team innovatively selected TP chemotherapy and treprizumab for combination in the final protocol design of the JUPITER-06 study, rather than the "fluorouracil + platinum" scheme commonly used in Europe and the United States, fully considering the characteristic differences and the tendency of previous treatment of esophageal squamous cell carcinoma patients in Asia, in order to customize the "Chinese protocol" for The Chinese people that is more suitable for local clinical practice.
The JUPITER-06 study (NCT03829969), published in Cancer Cell, is a randomized, double-blind, placebo-controlled, multicenter Phase III clinical study to evaluate the efficacy and safety of teriprumab plus TP chemotherapy (paclitaxel + cisplatin) and placebo combined with TP chemotherapy for advanced or metastatic ESCC first-line treatment. The findings have been recognized by the international academic community several times, and have been presented as oral presentations at the Annual Meeting of the European Society of Oncology (ESMO 2021) and the Annual Meeting of the Society for Cancer Immunotherapy (SITC 2021).
Co-corresponding author of jupiter-06 research publication Professor Wang Feng
From 28 January 2019 to 30 November 2020, the JUPITER-06 study included a total of 514 untreated patients with advanced or metastatic ESCC, randomly assigned to the triprimumab plus TP chemotherapy group (n=257) or placebo plus TP chemotherapy group (n=257), receiving up to 6 cycles of treatment with tereplimonab or placebo in combination chemotherapy regimen, respectively, followed by terepilimab or placebo maintenance therapy. The composite primary endpoints of the study were PFS and OS results assessed by the Blind Independent Review Committee (BICR) according to RECIST v1.1, and the secondary endpoints were the investigator-assessed PFS, objective response rate (ORR), and disease control rate (DCR).
The results showed that compared with chemotherapy alone, the combination of triprimumab significantly prolonged the patient's PFS (5.7 months vs 5.5 months), the risk of disease progression or death was reduced by 42% (HR= 0.58, P<0.0001), the proportion of patients who did not develop disease progression within one year was significantly increased (27.8% vs 6.1%), the median OS of patients was extended by half a year (17.0 months vs 11.0 months), and the risk of death was reduced by 42% (HR = 0.58, P=). 0.0004), indicating that the new therapy has achieved better survival benefits for more patients with advanced ESCC. At the same time, the ORR and DCR of patients in the triprimumab group were also significantly improved, as high as 69.3% and 89.1%, indicating that more patients had a shrinking tumor and alleviated symptoms after receiving treatment, which will increase confidence in their subsequent treatment. In terms of safety, triprimumab was added to the treatment on the basis of chemotherapy, and no new safety signals were found.
Professor Wang Feng said in introducing the results of the JUPITER-06 study: "The JUPITER-06 study successfully achieved a positive double endpoint result, which is exciting. In particular, the OS data performance, which is considered to be the 'gold standard' for tumor clinical benefit, the triprimumab combined with TP chemotherapy regimen has obvious advantages over chemotherapy alone, and the patient's median OS is extended by 6 months to 17 months, setting a new record for os treatment in the first line of first-line immunotherapy for advanced esophageal squamous cell carcinoma. In addition, we observed a significant 'smearing effect' from the Trepleizumab group, indicating that beneficiary patients are able to obtain stable, long-term results from immunotherapy on a sustained basis, which enables 'chronic disease' of esophageal cancer. ”
Based on the results of the JUPITER-06 study, the State Drug Administration (NMPA) accepted the market application for the marketing of a new indication for the treatment of locally advanced or metastatic esophageal squamous cell carcinoma in the first line of trepleimumab combined with platinum-containing chemotherapy in July 2021, and the US Food and Drug Administration (FDA) also granted the "orphan drug qualification" certification of triprimumab for the treatment of esophageal cancer, which will help accelerate the clinical trial and marketing registration progress of the drug in the United States.
[Reporter] Yan Huifang
【Author】 Yan Huifang
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