The 2023 European Society for Medical Oncology (ESMO) Annual Meeting was held on October 20 in Madrid, Spain. As one of the most prestigious and influential oncology conferences in the world, the oral presentation session will present the latest high-quality research data, and experts from around the world will discuss and share their views. With the development of medical technology and technology, the clinical treatment of malignant tumors is no longer limited to surgery, radiotherapy, and chemotherapy, and more and more new methods such as molecular targeted therapy and immunotherapy are applied to clinical practice, which greatly improves the success rate of clinical treatment of tumors and prolongs the life and quality of life of cancer patients.
In the field of oncology, there has always been a saying that "those who get lung cancer get the world". This is due to the fact that lung cancer is one of the most prevalent cancers in the world, with a large patient population. According to the 2022 National Cancer Report released by the National Cancer Center, in 2016, China had the highest incidence and mortality rates of lung cancer, with 828,000 new and 2.41 million lung cancer deaths, respectively. Due to the heterogeneity of lung cancer, treatment regimens often present very different treatment outcomes in different patients.
Different from chemotherapy drugs to trigger a therapeutic response, targeted therapy can selectively intervene in the growth, reproduction and metastasis of tumor cells through corresponding targets, with high efficacy and few side effects. Taking lung cancer as an example, lung cancer can be divided into small cell lung cancer and non-small cell lung cancer (NSCLC) according to cell morphology. RET fusions are a newly discovered lung cancer driver gene in the treatment of NSCLC, and the incidence of RET gene fusions in NSCLC is approximately 1.4%-2.5%.
The first approved RET inhibitor in China
The Phuket data ® is still impressive
It is worth mentioning that GAVRETIN ® (pratinib) was first approved for the treatment of RET fusion-positive locally advanced or metastatic NSCLC who have received prior platinum-based chemotherapy as early as March 2021. As the first approved selective RET inhibitor in China, GAVRETA ® fills the gap in the treatment of NSCLC with only EGFR, ALK, ROS1 and other targets. At present, GAVRETA ® has been approved for 3 indications in mainland China, covering the treatment of first-line and second-line NSCLC and first-line thyroid cancer.
In the international academic arena, the research of the pioneer Phuket is ® also highly recognized. In December 2022, CStone presented new data from the ARROW study at the European Society for Medical Oncology Asia Summit (ESMO Asia). The study is a global Phase I/II clinical study to evaluate the safety, tolerability and efficacy of pratinib (400mg) in patients with RET fusion-positive NSCLC, RET-mutant thyroid cancer, and other advanced solid tumors with RET fusions.
Data as of March 4, 2022, a total of 68 patients with advanced RET fusion-positive NSCLC from 10 Chinese research centers were included. This included 37 patients who had received prior platinum-based chemotherapy and 31 patients who had not received systemic therapy. The results showed that among patients who had received prior platinum-based chemotherapy (n=33), the confirmed objective response rate (ORR) was 66.7%, including 1 complete response (CR) and 21 partial response (PR); The disease control rate (DCR) was 93.9%. Among the patients who had not received systemic therapy (n=30), the ORR was 83.3%, including 2 CR and 23 PR. The DCR was 86.7%.
It is not difficult to see that whether the ORR of previously treated patients can reach 66.7%, or the treatment naïve patients achieve a higher response rate of 83.3%, GAVRETA ® has achieved very good clinical outcomes compared with traditional standard treatment. The ARROW study has been enrolled in China since 2019 and has been followed for more than three years, with median OS not yet reached. Previously, it was reported at the ESMO annual meeting that the median OS of pratinib in the global second-line NSCLC was 44.3 months, and the median first-line OS has not yet been reached. At the same time, pratinib was well tolerated, and it was generally safe and controllable in Chinese patients, and no new safety signals were found. Compared with the RET inhibitor research data presented at the 2023 ESMO Annual Meeting, GAVRETA ® data is still impressive.
In addition, in June 2023, the internationally renowned oncology journal Cancer published online the efficacy and safety updates of GAVRETAVA ® in the treatment of Chinese patients with RET fusion-positive NSCLC in the ARROW study. This is the second time that GAVAVA's ® clinical data in the Chinese patient population of RET fusion-positive NSCLC has been recognized by the international academic community, following the data presented at the European Society for Medical Oncology Asia Summit (ESMO Asia) in December 2022.
On August 9, 2023, the FDA approved the conversion of the RET fusion-positive NSCLC indication approved on September 4, 2020 to routine full approval (including first- and second-line NSCLC). At the same time, a randomized, open-label, phase 3 study of pratinib versus standard care for the first-line treatment of RET fusion-positive, metastatic NSCLC is ongoing (NCT04222972).
It is worth noting that point mutations and fusion mutations in RET genes can cause a variety of solid tumors, including NSCLC, papillary TC, colorectal cancer, ovarian cancer, pancreatic cancer, pleural mesothelioma, gastric cancer, and cholangiocarcinoma, and there is currently no effective treatment. The updated data of the global Phase I/II ARROW clinical trial of pratinib was published in the world's top medical journal Nature Medicine, which proves that GAVRETIN has good therapeutic efficacy in a variety of solid tumors with RET fusion-positive effects, providing preliminary data support for GAVRETINE's ® application in pan-tumor types, and its diagnostic value and commercial potential are expected to be further highlighted.
® This year's Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer 2023 Edition has upgraded GAVRETIN ® for the post-line treatment of stage IV RET fusion NSCLC to a level I recommendation, and added a new drug recommendation for the ® first-line treatment of stage IV RET fusion NSCLC. In the two years since its launch, China's real-world clinical experience has accumulated thousands of cases. CStone has achieved an 80% detection rate in GAVRET's ® leading hospitals, and has improved accuracy through collaboration with the National Center for Pathology Control.
Multiple indications have been approved
Accelerated commercialization benefits patients
It is understood that following the first approval of GAVRETIN for the treatment of RET-mutated locally advanced or metastatic NSCLC after prior platinum-containing chemotherapy in March 2021, GAVRET-viro ® was approved for the treatment of RET-mutated advanced thyroid cancer in March 2022, which is the first selective RET inhibitor for RET-mutant ® thyroid cancer in China, and its indication for pan-tumor is also being actively explored. GAVA ® has also been approved for marketing in Hong Kong and Taiwan. In June this year, CStone announced that GAVRETA was fully approved by the NMPA for the treatment of first-line RET fusion-positive NSCLC, and its applicable population has been significantly expanded compared with before, which is expected to significantly increase the sales of the drug, according to the estimation of Southwest Securities, GAVRETA ® ® sales in 2023-2025 are expected to reach 400 million yuan, 600 million yuan and 860 million yuan, respectively.
Thanks to CStone's outstanding clinical development strategy and execution capabilities, GAVRETA ® has a first-mover advantage in commercialization that is about one and a half years ahead of another RET inhibitor in China. Product approval is just the beginning, for CStone, "going to patients" is the core part of development, including many core elements, such as the number of cities where drugs are accessed, patients' ability to pay, precise target testing, and recognition by doctors and patients.
® According to CStone's semi-annual report, the company's precision therapeutics cover approximately 850 hospitals in more than 180 cities, 138 major commercial and government insurance plans in major regions such as Beijing, Shanghai, Guangdong, Zhejiang and Shandong, and complete the listing of approximately 330 hospitals and direct-to-patient specialty pharmacies (DTPs), covering a population of more than 100 million.
In addition to RET targets, the expression of the target tyrosine kinase (ROR1) has been significantly increased in a variety of hematological cancers and solid tumors, attracting the attention of scientists and pharmaceutical companies. Globally, two clinical-stage ROR1 ADCs have been acquired by multinational pharmaceutical companies for more than US$1 billion. Blood cancers that highly express ROR1 include B-cell chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL), non-Hodgkin lymphoma (NHL), and myeloid hematologic cancers. In solid tumors, ROR1-expressing cancer types include colon, lung, pancreas, ovarian, and other cancers. As a blockbuster product of CStone's pipeline 2.0 strategy, CS5001, a potential global best-in-class drug, is currently the world's second-fastest ROR1-ADC in clinical development, and its international multi-center first-in-human trials have been expanded from the United States and Australia to China. It is worth looking forward to the update of clinical safety and efficacy data by the end of 2023, so let's wait and see.