Prof. Caicun Zhou: Significantly prolong PFS, and Shuglizumab brings new first-line treatment options for metastatic NSCLC

*Only for medical professionals to read for reference, regardless of squamous or non-squamous NSCLC, sugarizumab combined with chemotherapy has significant PFS benefits! Lung cancer is currently the world's "number one cancer killer"
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According to the latest global tumor disease burden data released by the International Agency for Research on Cancer of the World Health Organization in 2021, the number of cases of lung cancer is 2.
2 million, ranking second in the global incidence of malignant tumors.
At the same time, lung cancer is also the cancer that causes the most deaths, accounting for about cancer.
18% of the total deaths (1.
8 million)
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The 2021 World Conference on Lung Cancer (WCLC) will be held in the form of an online virtual conference from September 8th to 14th.
Experts and scholars in the field of lung cancer from all over the world gather in the cloud to share the latest research progress in the field of lung cancer
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At this conference, the main researcher of GEMSTONE-302, Professor Zhou Caicun of Shanghai Pulmonary Hospital affiliated to Tongji University, shared the first-line treatment of metastatic non-small cell lung cancer with suglizumab or placebo combined with platinum chemotherapy in the form of an oral report (NSCLC) randomized, double-blind, phase III GEMSTONE-302 study results (abstract number: MA13.
07)
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▎The results of the study showed that the sugarizumab combined with chemotherapy group significantly prolonged progression-free survival (PFS: 9.
0 months vs 4.
9 months, HR 0.
48) compared with placebo combined with chemotherapy, and the overall survival (OS) data were also Shows the benefit trend
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In this regard, the Medical Oncology Channel is fortunate to invite Professor Zhou Caicun to make an in-depth interpretation of the research results and its clinical significance
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Wonderful video of Professor Zhou Caicun The GEMSTONE-302 study is uniquely designed: all patients in stage IV, full coverage of squamous and non-squamous NSCLC GEMSTONE-302 is the first to be evaluated in patients with squamous or non-squamous NSCLC (regardless of PD-L1 expression) A randomized, double-blind phase III trial of the efficacy and safety of PD-L1 monoclonal antibody combined with platinum-based chemotherapy
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The study included no previous chemotherapy, measurable lesions (according to RECIST v1.
1), ECOG performance status (PS) score of 0-1, no known EGFR/ALK/ROS/RET mutations, and tumor tissues that can be used to detect PD -L1 expression stage IV NSCLC (squamous and non-squamous) patients
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Randomly assigned to suglimumab combined chemotherapy group (n=320) or placebo combined chemotherapy group (n=160) at 2:1
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GEMSTONE-302 research design Professor Zhou Caicun pointed out that the GEMSTONE-302 research design has its uniqueness
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Different from other immunotherapy studies, all patients included in the GEMSTONE-302 study were stage IV NSCLC patients, and the study included both squamous and non-squamous patients, achieving full coverage of squamous and non-squamous NSCLC patients
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In addition, previous studies of immuno+chemotherapy with positive results were mainly PD-1 monoclonal antibody combined with chemotherapy compared with placebo combined chemotherapy, while the GEMSTONE-302 study was successful with PD-L1 monoclonal antibody combined with chemotherapy compared with placebo combined chemotherapy
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"At the beginning of the clinical study, we were also a little worried because the previous studies of PD-L1 monoclonal antibody combined with chemotherapy did not achieve consistent results
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However, the efficacy of suglimumab was very good, and the final study obtained a positive result
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This is also our comparison Proud place
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" Professor Zhou Caicun said that good clinical research design is very important
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In the first-line treatment of sugarizumab combined with chemotherapy for stage IV NSCLC, regardless of the pathological type and PD-L1 expression, PFS was significantly prolonged at the WCLC in 2021.
Professor Zhou Caicun shared the final PFS results of the GEMSTONE-302 study and the preliminary OS results
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As of March 15, 2021, with a median follow-up of 18 months, among the enrolled 479 patients, 79 (24.
7%) and 12 (7.
5%) patients in the sugarizumab group and placebo group, respectively Under treatment
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The results of the study showed that in the intention-to-treat (ITT) patients, the combination of suglizumab and chemotherapy can prolong the median PFS by 4.
1 months; the median PFS evaluated by the investigators in the suglizumab group and the placebo group was 9.
0 respectively At 4.
9 months and 4.
9 months (HR 0.
48), the 12-month PFS rates were 36.
4% and 14.
8%, respectively
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GEMSTONE-302 study ITT population PFS results OS data is not yet mature, but the benefit trend is significant
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The initial OS of sugarizumab group and placebo group were 22.
8 months and 17.
7 months (HR 0.
67), and the 24-month OS rate was 47.
1% and 38.
1%, respectively
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GEMSTONE-302 study ITT population OS results The objective response rate (ORR) evaluated by the investigators in the Shuxgliumab group and the placebo group were 63.
4% and 40.
3%, respectively, and the median duration of response (DoR) was 9.
8 months and 4.
4 months
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Professor Zhou Caicun said that although the OS data is not yet mature, the OS curves of the two groups of patients have been separated, suggesting that with the extension of follow-up time, the OS of the sugarizumab group will still be further improved
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"I am very confident that the OS studied by GEMSTONE-302 will have a positive result
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"In addition, Professor Zhou Caicun emphasized that in combined immunotherapy, if the DoR is significantly prolonged, it means that the main effect is the efficacy of immunotherapy; if the DoR is short, it is more likely that chemotherapy plays a major role
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In the GEMSTONE-302 study, Shuge The median DoR of the Lizumab group was significantly prolonged, which was more than twice that of the placebo group, indicating that the efficacy of Shuglizumab was significant
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In all subgroup analyses, significant results were observed in combination with Shuglizumab and chemotherapy.
PFS benefit
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In patients with squamous NSCLC, the median PFS of sugarizumab group and placebo group were 8.
3 and 4.
8 months (HR 0.
34), respectively; in patients with non-squamous NSCLC, the median PFS of the two groups were respectively It was 9.
6 and 5.
9 months (HR 0.
59)
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Similarly, regardless of the expression level of PD-L1, the PFS of the suglimumab group compared with the placebo group had a benefit
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In patients with PD-L1<1%, The median PFS in the two groups were 7.
4 and 4.
9 months (HR 0.
55), respectively; among the patients with PD-L1 1% to 49%, the median PFS was 8.
8 and 4.
8 months (HR 0.
53), respectively; in PD-L1≥ In 50% of patients, the median PFS was 12.
9 and 5.
1 months (HR 0.
41), respectively
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GEMSTONE-302 study PFS results in patients with squamous and non-squamous NSCLC.
In addition, the combination of suglizumab and chemotherapy is well tolerated.
No new safety signals have been found
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Shuglizumab: fully human PD-L1 monoclonal antibody with unique mechanism of action and better safety.
Shuglizumab's excellent efficacy and safety and its optimized antibody structure and unique The mechanism of action is closely related
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Professor Zhou Caicun, Shuglizumab has the following characteristics in drug design and mechanism: First, Shuglizumab is a full-length fully human IgG4 anti-PD-L1 monoclonal antibody, which has a higher probability of inducing anti-drug antibodies (ADA).
It is low, so it is less likely to cause adverse reactions such as fever and infusion reactions, and avoids the influence of ADA on the efficacy of the drug
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Secondly, as the only PD-L1 inhibitor of IgG4 subtype, sugarizumab retains antibody-dependent cell-mediated phagocytosis (ADCP), which can mediate macrophages to directly kill tumors, thereby further enhancing the antigen Presented to stimulate the immune system to achieve long-term effects
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Finally, compared to PD-1 monoclonal antibody that simultaneously blocks the binding of PD-1 and PD-L1 and PD-L2, sugarizumab, as a PD-L1 monoclonal antibody, only blocks the combination of PD-1 and PD-L1.
The combination of PD-1 and PD-L2 is retained, suggesting that it has more advantages in reducing immune-related adverse events
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In summary, the GEMSTONE-302 study reached the main research endpoint.
The PFS benefit of sugarizumab combined with chemotherapy is significant, and the OS data is also encouraging, and the benefit trend is significant; moreover, whether it is squamous cell carcinoma or non-squamous cell carcinoma, regardless of PD- Whatever the expression status of L1, there are significant PFS benefits! As the first domestic PD-L1 monoclonal antibody to prove that combined chemotherapy significantly improves the PFS of Chinese NSCLC patients, sugarizumab is expected to become the world's first combined chemotherapy to be approved for both squamous and non-squamous stage IV NSCLC first-line treatment of PD-L1 Monoclonal antibodies bring new first-line treatment options for such patients
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Expert profile Prof.
Caicun Zhou Chief physician, professor, and doctoral supervisor of the Institute of Oncology, Tongji University School of Medicine, Shanghai Pulmonary Hospital, Tongji University.
Chairman of the Committee, Chinese Medical Promotion Association Thoracic Tumor Branch Chairman, Shanghai Anti-Cancer Association, Lung Cancer Molecular Targeting and Immunotherapy Committee Chairman, China East and West Lung Cancer Research Collaboration Group (E-WEST), CSCO Translational Tumor Medicine Committee Chair-designate of the Chinese Anti-Cancer Association Oncology Drug Clinical Research Special Committee Chair-designate Member of the International Association for Lung Cancer Research (IASLC) Education Committee Member of the International Association for Lung Cancer Research (IASLC) Tobacco Control Committee Member enjoys special allowance from the State Council Shanghai Leading Talent, Shanghai The person in charge of the city’s most important key discipline of respiratory medicine has received funding for nearly 20 scientific research projects, including the National 863 Program, the National Natural Science Foundation of China, etc.
to lead or participate in more than 30 large-scale clinical researches, and publish more than 200 papers.
Second Prize of Progress, First Prize of Shanghai Science and Technology Progress, First Prize of Science and Technology of China Anti-Cancer Association, First Prize of China Medical Science and Technology Prize, First Prize of Shanghai Medical Science and Technology Prize, Shanghai Good Doctor Scientific information provided by people does not represent the views of this platform