On June 22, the sixth live broadcast of "Drug Precision" series of live broadcast columns "Focusing on Drug Targets and Precision Accompaniment" jointly planned by Genetron and Translational Medicine Network came to a successful conclusion. This live broadcast focused on the cutting-edge of NTRK gene fusion targeted therapy, Hot topics such as clinical research progress on NTRK gene fusion inhibitors and clinical detection of NTRK gene fusion mutations were launched.
Dr. Ren Yizhong, Director of Baoyuan Biomedicine , gave a report entitled "NTRK Inhibitors: From Basics, Detection to Clinical Development".
Dr. Ren first explained the fusion and mutation of NTRK gene, and then reviewed the timeline of NTRK inhibitors from basic to clinical development. Studies have found that NTRK gene fusions are widespread in common adult and pediatric tumors, and there is also great uncertainty about NTRK fusions with other genes. Research data shows that NTRK fusion is rare in common tumors, and experiments show that only 0.21% of patients per 10,000 people contain [1] .
Dr. Ren analyzed the advantages and disadvantages of IHC, FISH and NGS detection methods, which is beneficial to the construction of different clinical experimental models. Several different NTRK inhibitors are then introduced.
finally concluded that currently existing drugs have good effects on inhibiting NTRK, and accurate detection of is a key factor in drug development and later clinical trials .
Dr. Ren Yizhong is currently the medical director of Baoyuan Biomedical Technology (Hangzhou) Co., Ltd., and was the deputy director of translational medicine of Beida Pharmaceuticals. He is mainly engaged in tumor molecular diagnosis and clinical development of innovative drugs, and has an in-depth understanding of the current international Knowledge of trends and important targets in tumor drug development, development of tumor drug molecular markers (biomarkers), and clinical trials of tumor drugs. Dr. Ren holds a bachelor's degree in clinical medicine from Anhui Medical University and a doctorate in science from the University of Science and Technology of China.
Baoyuan Biotechnology Ren Yizhong
Next, Dr. Wang Yukun from Bayer China R&D Center shared the "Overview of Larotrectinib Clinical Research and Development in China".
Dr. Wang started by explaining the pathogenesis of NTRK gene fusion as an oncogenic driver. The NTRK gene fusion leads to the overexpression of downstream TRK fusion proteins, and the positive rates of tumors in different pathological subtypes vary greatly. Larotrectinib only specifically binds to TRK kinase and does not interact with an additional 82 receptors, enzymes, and nuclear targets at clinically or toxicologically relevant concentrations.
Dr. Wang then presented in detail the clinical data of larotrectinib in the treatment of TRK gene fusion-positive tumors. The treatment data of larotrectinib were analyzed from several dimensions such as overall response rate, treatment onset time, efficacy maintenance time and safety.
At the end of the report, Dr. Wang shared the clinical research and development process of larotrectinib in China, considering both patients and researchers to carry out relevant clinical research, and looking for suitable testing companies and trustworthy laboratories . After experiencing multiple IND and NDA submission communications, based on the clinical data of Chinese patients, CDE responded in March 2021 agreeing to NDA submission. Dr. Wang also shared with us his experience in the research and development of the new drug larotrectinib, such as how to formulate innovative clinical research and development strategies, how to conduct groundbreaking Chinese data analysis and submission, and how to communicate with regulatory authorities in a timely manner.
Dr. Wang Yukun has professional physician licenses in China and the United States. He has accumulated more than 20 years of rich experience in basic medicine, clinical medicine and drug research and development. He has worked for Pfizer and Bayer Healthcare Co., Ltd. . Currently, he is the head of translational cancer medicine at Bayer China R&D Center.
Bayer China R&D Center Wang Yukun
The last report was "NTRK gene fusion clinical treatment progress" brought by Professor Ren Shengxiang from Shanghai Pulmonary Hospital Affiliated to Tongji University. Professor Ren’s sharing started from two aspects: NTRK background, current treatment status, and NTRK target research hot spots.
Professor Ren first elaborated on the pathogenesis characteristics of NTRK and its relationship with other genes. Then he introduced the similarities and differences between the two inhibitors in clinical application, pointing out that larotinib is a highly selective drug specific for TRK tumors, and ENTRECTINIB is a multi-target small molecule inhibitor.The effectiveness and survival data of the two inhibitors larotrectinib and ENTRECTINIB in the clinical treatment of lung cancer can achieve the expected results. Professor Ren pointed out that because there are differences in the starting point of research between the two, there is no comparison between which one is higher and which one is lower. After matching correction, the safety data showed that larotrectinib was better tolerated and had a better safety profile. The last professor of
gave an outlook on the future research hotspots of NTRK, and also explained in detail the drug resistance mechanisms caused by different reasons. For drug resistance caused by TRK secondary mutations, comparing the resistance mechanism of On-target and the resistance mechanism of Off-target, targeting drug sensitivity from the same mutation site of and will be a research hotspot.
Professor Ren Shengxiang is a chief physician and doctoral supervisor. He is currently the administrative deputy director of the Oncology Department of Shanghai Pulmonary Hospital Affiliated to Tongji University. He also serves as a member of the IASLC Education Committee, the Secretary-General of the Thoracic Oncology Branch of the China Association for the Promotion of Medical Care, the Vice-Chairman of the Youth Committee of the Oncology Drug Clinical Research Committee of the Chinese Anti-Cancer Association, and the Vice-Chairman of the Lung Cancer Molecular Targeted Immunotherapy Committee of the Shanghai Anti-Cancer Association. , Vice Chairman of Youth Committee of Shanghai Medical Association Tumor Target Molecular Specialty Branch, Standing Member of CSCO Non-Small Cell Lung Cancer Committee, Standing Member of CSCO Youth Committee, Member of CSCO Immunology Expert Committee, Member of CSCO Expert Committee on Geriatric Cancer Prevention and Treatment, Chinese Geriatrics Association Standing member of the Oncology Professional Committee, and standing member of the Oncology Respiratory Endoscopy Professional Committee of the Shanghai Anti-Cancer Association. The clinical focus is on the precision treatment of advanced lung cancer. He has published more than 60 SCI papers as the corresponding or first (including co-author) in journals such as Ann Oncol, Nat Commun, Molecular Cancer, STTT, JTO, CCR, Cancer Immunol Res, and JHO. Selected as Shanghai's outstanding academic leader , Shanghai Dawn Plan, Pujiang Talent Plan, Shanghai Talent Development Plan; won the second prize of the National Science and Technology Progress Award (6/10), and the first prize of the Shanghai Science and Technology Progress Award (2/10) , US-CACA Scholar, IASLC Scholar Award and Shanghai Medical System " Silver Snake Award ", etc.
Shanghai Pulmonary Hospital Affiliated to Tongji University Ren Shengxiang
The discussion session was moderated by Dr. Ren Yizhong, and the three experts had a lively and thorough discussion.
Regarding the current NTRK gene testing, Dr. Wang Yukun compared the current status of NTRK standardized testing at home and abroad: Due to different medical insurance policies in foreign countries, NGS testing can be more widely promoted among patients; while in China, the testing cost is relatively expensive , which may As patients understand the drug and the drug is commercialized, more and more patients will be able to see its use.
Professor Ren Shengxiang also pointed out that many clinical hospitals now have testing platforms, which have attracted enough attention from the industry. In the future, NTRK patients can better receive targeted therapy. Professor Ren believes that NTRK-driven gene diagnosis has the characteristics of "low incidence and high attention" . This is because in clinical treatment, the effect of directly clearing cancer cells can be achieved through safe medication, which will give patients greater surprises. . In addition, there are also the characteristics of patients with longer survival period and higher drug safety than .
Then, Dr. Wang Yukun said that patients have high expectations for NTRK inhibitors because of their good efficacy and cross-tumor characteristics. It is believed that with mature detection methods, larotrectinib will gain the trust of more patients after it is launched on the market. Professor Ren Shengxiang also pointed out that through testing recommendations, media recommendations, patient education and medical care education , more patients can understand and receive better treatment.
Regarding the topic of how to benefit more patients, Dr. Wang Yukun pointed out that, as Professor Ren said, more parties need to coordinate, promote, and let more patients know about this drug, so that more relevant patients can benefit. Professor Ren also proposed that economic factors should be taken into consideration, and measures such as increased aid, funding and cooperation are needed for economically underdeveloped areas; in addition, better drug development is also very important to address the problem of late-stage drug resistance to .
Dr. Ren Yizhong concluded in his final speech that he hoped that testing companies, pharmaceutical companies and clinical hospitals would work together to make NTRK inhibitors benefit more patients.
Discussion
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This live broadcast ended successfully with all the guests and viewers still having fun! Precision medicine, diagnosis first, this series of live broadcasts aims to promote academic exchanges on innovative drug research and development, assist high-quality research and development of innovative drugs, and jointly promote the research and development exploration and industry thinking of Chinese pharmaceutical innovative enterprises. The "Drug Precision" column uses a combination of online live broadcast and offline meetings. is issued once a month. Everyone is welcome to continue to use the Translational Medicine Network public account , Genetron Health's online public account, and the "Drug Precision" WeChat group Come to get live information and participate in discussions!
References:
[1] Zoran Gatalica, Jeffrey Swensen, Jeffery Kimbrough, Joanne Xiu; Abstract A047: Molecular characterization of the malignancies with targetable NTRK gene fusions. Mol Cancer Ther 1 January 2018; 17 (1_Supplement): A047. https: //doi.org/10.1158/1535-7163.TARG-17-A047
