Gastrointestinal cancer: conservatively advance ASCO 2021

Click on the title below to read the relevant report of ASCO2021.
Chinese company R&D military report.
Who leads the field of lung cancer and embraces Asia: Junshi nasopharyngeal cancer research is selected for LBA Yasheng: Esophageal and gastrointestinal tumors entering the harvest period are high-incidence diseases of Chinese patients, and they are also very important in tumor treatment.
The thorny issue is that the treatment options available for advanced patients are very limited, which is a severely unmet clinical need and has a huge market potential
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However, R&D companies are also well aware of the difficulty of product development in this field of indications, and most of the research is at the stage of careful testing of the water
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For more detailed analysis of the 2021ASCO annual meeting, please contact mc@pharmaDJ.
com to purchase esophageal cancer: IO brings a glimmer of light Tumor immunotherapy (IO) has been high hopes in the treatment of advanced esophageal cancer in recent years
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In the past, the standard first-line treatment recommended by the guidelines for advanced esophageal cancer was chemotherapy.
In April this year, the Chinese Society of Clinical Oncology (CSCO) released the "2021 version of the guidelines for diagnosis and treatment of esophageal cancer", which recommended PD-1 inhibitors for the first-line advanced metastatic esophageal cancer for the first time.
Treatment
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The summary of the selection of Chinese companies into ASCO also reflects this trend.
Many domestic companies are exploring tumor immunotherapy for the treatment of esophageal cancer
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A total of 6 companies’ 8 products and 13 studies are related to esophageal cancer, of which 6 products involve tumor immunotherapy
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Hengrui Medicine's PD-1 inhibitor carrelizumab is even more heavily supported in this indication.
There is a phase III registration study and multiple neoadjuvant therapies, as well as a real-world study data released
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At the end of last year, Hengrui Medicine issued an announcement stating that the ESCORT-1st study of carrelizumab combined with paclitaxel and cisplatin for the first-line treatment of advanced esophageal cancer has reached the pre-designated superiority standard and has submitted the indication Listing application
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It is the data of this research that was published on ASCO this time
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Judging from the results of the study, this combination regimen improves the overall survival (OS) and progression-free survival (PFS) of patients, and other secondary indicators are also better than the control group (see the figure below)
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In March of this year, the FDA approved Merck’s PD-1 inhibitor pembrolizumab in combination with platinum-containing chemotherapy for the first-line treatment of unresectable or locally advanced or metastatic esophageal cancer or gastroesophageal junction that is not suitable for radical radiotherapy and chemotherapy Department of cancer
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This product is only approved for the second-line treatment of advanced esophageal cancer in China.
If Hengrui can be approved for the first-line indication first, it is estimated that it will soon take advantage of the new guidelines to open the esophageal cancer market
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In addition to this study, Hengrui has also carried out 3 studies on neoadjuvant treatment of esophageal cancer.
The options of choice are carrelizumab + chemotherapy or carrelizumab + apatinib + chemotherapy.
These studies are still early studies, but the results suggest that neoadjuvant therapy related to tumor immunity may improve the prognosis of patients with esophageal cancer after surgery, but this conclusion needs to be proved by a phase III study
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At the same time, the results of a real-world study of Karelizumab monoclonal antibody involving 228 patients also brought new hints to the clinical selection of PD-1 inhibitors for the treatment of esophageal cancer
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In the study, 26.
2% of patients received first-line treatment, 33.
6% of second-line treatments, and 35.
4% of third-line and above treatments.
Most patients were combined with chemotherapy or anti-angiogenesis drugs.
The results of the study showed an objective response rate (ORR) of 13.
1%.
The disease control rate (DCR) is 80%
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It is worth noting that BeiGene and Corning Jerry are exploring new therapies for two tumor immune targets at the same time in the indication of esophageal cancer.

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BeiGene uses a combination of TIGIT monoclonal antibody ociperlimab + PD-1 monoclonal antibody tislelizumab, and Kang Ning Jereh's medication plan is PD-L1-CTLA4 double antibody KN046 single-agent treatment
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Both studies are in the early stages
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The BeiGene study has no data published in the abstract, but the information on ClinicalTrial.
gov shows that the study is expected to include 280 subjects.
It is a global multicenter randomized double-blind placebo-controlled study.
In view of the study The design and large sample size, the future results are worth looking forward to
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Corning Jerry’s Phase II study included 15 patients, with an ORR of 53.
3% and a DCR of 91.
6%.
However, the data in this study is relatively small, and we will continue to see the release of new research results in the future
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The only study of a small molecule TKI drug comes from Zhengda Tianqing’s Anlotinib.
This II study for the treatment of patients with first-line advanced or metastatic esophageal squamous cell carcinoma has good results.
The research plan is Anlotinib.
Rotinib + chemotherapy, 45 patients participated, the ORR was 79.
4%, the DCR reached 100%, and the median PFS was 9.
76 months.
However, the study is still in its early stage, with a small sample size, and lack of baseline data for patients
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Gastric cancer: Under the cloud, we only dare to make small steps toward advanced gastric cancer.
The current standard therapy is still chemotherapy.
If the disease still progresses after receiving multiple chemotherapy, patients may try targeted drugs or tumor immunotherapy, but the research in this field is overall From the point of view, failure is more than success, and many well-known drugs have suffered from this indication
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In this ASCO, 11 research abstracts related to Chinese innovative products in gastric cancer were found, but it can be seen that the common characteristics of these studies are that they are all early studies, the research scale is small, the number of subjects is small, and the subjects of these studies There were no more than 50 participants, and most studies did not set up a control group
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Research on PD-1 inhibitors in other indications is very lively, but it does not catch a cold against gastric cancer.
Only Hengrui has carried out two small-scale explorations, and Sofatinib of Hutchison Medicine has attracted the attention.
Real Teriplizumab has carried out research on combination medications
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This year's research in this field still shows a characteristic: Many Chinese companies' products have begun to focus on HER2-positive gastric cancer
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Hengrui's HER2 inhibitor pyrrotinib + CDK4/6 inhibitor SHR6390, Kang Ning Jereh's HER2 double anti-KN026, and Xinma Bio's HER2-ADC (antibody-conjugated drug) ARX788 all target this indication
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The study of Corning Jerry KN026 once again proves the therapeutic effect of this product in HER2-positive tumors
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The results of the study showed that the HER2-positive patients enrolled in the study could benefit from KN026 treatment, regardless of whether they had received other HER2 inhibitor treatment before, especially in the HER2 high expression group, the ORR of the patients was 55.
6%
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In addition, by comparing the data of the HER2 high expression group and the HER2 low expression group, it can be found that the therapeutic effect of KN026 is positively correlated with the amount of HER2 expression.
This result also suggests that KN026 effectively inhibits the HER2 target (see the figure below)
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Last year, there was also a clinical trial of KN026 combined with KN046 (PD-1-CTLA4 double antibody) initiated by researchers
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The results showed that the objective remission rate of KN046 combined with KN026 in HER2-positive solid tumors was 64.
3%, and the disease control rate was as high as 92.
9%
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At present, KN026+KN046 combination therapy for the treatment of HER2-positive or HER2-low expression gastric cancer and gastroesophageal junction cancer has been approved by the FDA as an orphan drug
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The data released this time once again illustrates the development potential of KN026 on this target and related indications
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Colorectal cancer: exploring the combined use of IO and targeted drugs in the field of colorectal cancer.
The research of Chinese companies selected by ASCO is similar to that of gastric cancer, and most of them are small-scale early studies.
However, there is an obvious trend in colorectal cancer research to combine tumor immunity with Targeted drug combination
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Hengrui Medicine, Jiahe Bio, Hutchison Medicine, and Cinda Bio are all involved in exploring similar research programs
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Among a number of studies, the phase Ib study of Fruquintinib combined with Sintilimab in the treatment of advanced colorectal cancer conducted by Hutchison Medicine and Innovent Biopharmaceuticals has the largest sample size (see the figure below)
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This study is an extended cohort study of Fruquintinib + Sintilimab after completing Phase I dose exploration.
There are 44 subjects in total, which are evenly allocated to two groups
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As can be seen from the above figure, the two groups of patients received the same treatment drugs, and the only difference was the dosage and frequency of Fruquintinib
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Overall, the therapeutic effect of the 5mg high-dose group is better than that of the 3mg low-dose group.
Both the objective remission rate and the progression-free survival are longer than the low-dose group
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At the same time, we can see an interesting phenomenon: in the incidence of more serious adverse reactions, the incidence of 5mg group is lower
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The results of this study may provide references for key medication regimens for further studies of this combination in the future
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In recent years, the precision treatment of advanced bowel cancer has also made great progress
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Studies have performed genotyping of tumors in patients with advanced colon cancer.
The most common is RAS mutations, with KRAS and NRAS mutations accumulating 45% to 60%; secondly, BRAF mutations have an incidence of about 10%, but these patients have a special course of disease.
It is dangerous; next is HER2 amplification, which requires anti-HER2 treatment; in addition, dMMR or MSI-H changes and NTRK gene fusion are rare
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For these specific types of colorectal cancer with gene mutations, this ASCO abstract has a number of studies on domestic innovative drugs: Hengrui Medicine’s pyrrotinib + trastuzumab study is aimed at HER2-positive advanced colorectal cancer, MEK1/2 The inhibitor SHR7390 + carrelizumab is aimed at the advanced colon cancer of MSI-H.
Anlotinib combined with CAPEOX chemotherapy is exploring the first-line treatment of RAS/BRAF wild-type unresectable metastatic colorectal cancer
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The Phase II study of Anlotinib, code-named ALTER-C002, from November 2019 to February 2021, a total of 31 patients were enrolled, with an ORR of 81.
5% and a DCR of 100%.
The PFS has not yet been reached.
The results of the study suggest that this program has a good therapeutic potential for RAS/BRAF wild-type advanced colorectal cancer.
A multi-center phase III double-blind controlled study is being initiated to further prove its efficacy
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In general, for esophageal and gastrointestinal tumors, various companies have been cautious in conducting research in this field, and have not taken any particularly big steps at will
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A few early studies have shown therapeutic potential, but the efficacy and safety have yet to be further confirmed
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