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On July 8, 2022, Innovent Biotechnology announced that the first prescription of dabotan ® (pemitinib), the world's first targeted drug for bile duct cancer, was prescribed by Professor Zhou Jian, vice president of Zhongshan Hospital affiliated to Fudan University, marking the official entry of Dabotan ® into clinical application, bringing a new choice of international quality treatment to Chinese patients with cholangiocarcinoma, and opening a new era of targeted treatment for cholangiocarcinoma.
Professor Zhou Jian, the first prescriber of Dabtan ® (pemetinib) and the main investigator of his registered clinical study CIBI375A201, said: "Patients with cholangiocarcinoma are facing the survival dilemma of rapid progression and poor efficacy of traditional chemotherapy, and urgently need new treatment methods. Compared with traditional chemotherapy, pemetinib can be completed by oral administration and shows significant advantages in clinical efficacy and safety. The listing of pemetinib has made a new breakthrough in the second-line treatment of advanced cholangiocarcinoma, which has been silent for nearly a decade. As a researcher and a doctor who treats hepatobiliary tumors, I am very happy. ”
Dabtan ® Pharmacy Information
Cholangiocarcinoma is a malignant tumor with a high fatality rate, and surgery is the only treatment for radical treatment, but due to its non-specific clinical manifestations, most patients often lose the opportunity for radical surgery due to local invasion or distant metastasis at the time of initial presentation [1]. In the past ten years of treatment, there has been little progress in the systematic treatment of advanced cholangiocarcinoma, and chemotherapy is the main treatment method, but the efficacy is not good. There is a huge unmet treatment need in Patients with Cholangiocarcinoma in China.
In recent years, with the vigorous development of new sequencing technologies such as genomics, FGFR2 fusion/rearrangement has been found to be an important molecular pathological mechanism driving the occurrence and development of bile duct carcinoma diseases, and has also become an important clinical progress in the treatment of cholangiocarcinoma in the past decade[2].
Dabactam ® (pemetinib) is a potent and selective small molecule oral inhibitor of FGFR1/2/3 that inhibits phosphorylation of FGFR1/2/3 while blocking cell proliferation signals by blocking the activity of the FGFR kinase domain in binding to ATP, thereby inhibiting tumor growth[3]. A Chinese-registered clinical trial has shown that patients with bile duct cancer who receive dabrate (pemetinib) monotherapy with dabrate ® (pemetinib) have a recent objective response rate (ORR) of 56.7% and a median progression-free survival (mPFS) of 9.6 months [4], and some patients are still being followed up. This is a major survival breakthrough compared to the 5% ORR of chemotherapy[5].
Mr. Liu Min, Chief Commercial Officer of Cinda Biopharma Group, said: "The registered clinical study of Dabotan ® began the first patient enrollment in March 2020 and the last patient enrollment in December of the same year, which can be said to be very fast for a rare molecular variant type with an incidence rate of only 6.14%. Many thanks to all the researchers involved in this study for their great contribution to the early use of this precision targeted drug with significant efficacy in Chinese cholangiocarcinoma patients. In addition, in order to allow patients who are in urgent need of effective treatment to use Dabotan ® as soon as possible, the business team of Cinda Biologics and R&D, production, registration, supply chain, channel commerce and other departments have achieved the landing of this valuable prescription through cooperation, continuous relay and acceleration of each link. ”
About advanced cholangiocarcinoma and FGFR gene variants
Cholangiocarcinoma is a malignant tumor originating from bile duct epithelial cells, which can be divided into two categories: intrahepatic bile duct carcinoma and extrahepatic bile duct carcinoma according to the site of occurrence. In recent years, the incidence of cholangiocarcinoma has increased year by year, and surgery is the only treatment with curative potential. However, most patients with cholangiocarcinoma are unresectable tumors or metastases at the time of initial diagnosis, losing the opportunity for surgical radical treatment. In patients with non-resectable, metastatic, or postoperatively recurrent cholangiocarcinoma, the first-line standard of care is cisplatin plus gemcitabine, which is less than satisfactory and has an overall survival of less than 1 year.
FGFR gene variants are present in many types of human tumors, mainly through FGFR gene amplification, mutation, chromosomal translocation, and ligand-dependent activation caused by FGFR signal abnormalities. Fibroblast growth factor receptor signaling promotes the development of malignant tumors by promoting tumor cell proliferation, survival, migration, and angiogenesis. The results of early clinical studies, including selective FGFR inhibitors in Pemazyre® (pemetinib), showed that these drugs have a tolerable safety and have initial signs of clinical benefit in the presence of subjects with FGF/FGFR variants.
About Dabtan ® (pemetinib)
Dabertan ® (pemetinib) is a potent selective oral inhibitor of FGFR subtype 1/2/3. In April 2020, the U.S. Food and Drug Administration (FDA) approved Incyte's Pemazyre® for the treatment of advanced/metastatic or unresectable FGFR2 fusion/rearrangement cholangiocarcinoma in previously treated adults (confirmed by FDA-approved testing methods). Continued approval of this indication may depend on the validation and description of clinical benefit in confirmatory trials.
In Japan, Pemazyre® is approved for the treatment of unresectable biliary carcinoma (BTC) with the FGFR2 fusion gene and worsening after chemotherapy.
In Europe, Pemazyre® is approved for the treatment of locally advanced or metastatic cholangiocarcinoma with FGFR2 fusion or rearrangement in adult patients who have progressed after at least one previous systemic treatment. Pemazyre® is sold by Incyte in the United States, Europe and Japan.
In December 2018, Innovent Bio and Incyte reached a strategic collaboration on three clinical trial candidates discovered and developed by Incyte, including Pemigatinib. Under the terms of the agreement, Cinda Bio has development and commercialisation rights for pemigatinib in Chinese mainland, Hong Kong, Macau and Taiwan.
In March 2020, a key trial conducted by Innovent Biologics in China for patients with advanced cholangiocarcinoma has completed the first patient administration. In June 2021, pemetinib (Chinese trademark: Dabtan ®) was approved by the Food and Drug Administration (TFDA) of the Ministry of Health and Welfare of Taiwan for the treatment of locally advanced or metastatic cholangiocarcinomas in adults who have received systemic drug therapy, tumors with fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement, and cannot be surgically removed.
In July 2021, the State Drug Administration (NMPA) formally accepted the listing application for the treatment of adult patients with advanced, metastatic or non-surgically resectable cholangiocarcinoma with FGFR2 fusion or rearrangement for pemetinib (Chinese trademark: dabtan ®) for treatment of at least one systemic treatment in the past and confirmed by testing. In January 2022, pemetinib (Chinese trademark: dabtan ®) was approved by the Department of Health (DH) of the Government of the Hong Kong Special Administrative Region for the treatment of locally advanced or metastatic cholangiocarcinomas in adults who have received systemic drug therapy, fusion or rearrangement with fibroblast growth factor receptor 2 (FGFR2), and are not surgically removable.
In March 2022, pemetinib (Chinese trademark: dabtan ®) was approved by the State Drug Administration (NMPA) for the treatment of adult patients with advanced, metastatic or non-surgically resectable cholangiocarcinoma who had previously received at least one systemic treatment and had been tested to have FGFR2 fusion or rearrangement.
The first-line clinical trial of dabtan ® (pemetinib) cholangiocarcinoma is currently underway (CTR20201757).
Bibliography:
[1] Banales J M, et al. Nature Reviews Gastroenterology & Hepatology,2016,13(5):261-80.
[2] Irina S Babina, Nicholas C. Nat Rev Cancer. 2017,17(5):318-332.
[3] Nicholas Turner, Richard Grose. Nat Rev Cancer. 2010,10(2):116-29.
[4] Innovent data on file
[5] Daniel H, et al. Lancet Oncol. 2021;22:690-701.
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