China-Based Immunotherapy Company Receives FDA’s Orphan Drug Designation for Advanced Gastric Cancer Treatment
By Judy Ya-Hsuan Lin
Gastric cancer ranks top three in cancer-related mortality and is considered one of the most incurable cancers worldwide. Patients with gastric and gastroesophageal junction cancer type have less than 10 months of median overall survival. According to the WHO, approximately 1,030,000 new cases of gastric adenocarcinoma are expected each year.
In China, the annual incidence of gastric cancer exceeds 600,000 cases. Although the current FDA-approved treatments include human epidermal growth factor receptor-2 (HER-2) targeting therapy Trastuzumab, anti-VEGFR-2 monoclonal antibody Ramucirumab, and immune checkpoint inhibitors such as anti-PD-L1 monoclonal antibody Avelumab, there is always room to develop advanced treatments for a large population of patients.
Orphan Drug Designation
Founded in 2014, CARsgen Therapeutics, a clinical-stage biopharmaceutical company based in China, has established a broad pipeline of CAR T-cell product candidates covering several solid and blood tumor types. On October 5th, CARsgen announced that the USFDA had granted orphan drug designation to its humanized anti-claudin18.2 autologous chimeric antigen receptor (CAR) T-cell drug candidate, CT041, for the treatment of gastric and gastroesophageal junction adenocarcinoma.
IND Clearances for CAR T-Cell Candidate
CT041 received its Investigational New Drug (IND) clearances both from the USFDA and the National Medical Products Administration (NMPA) in China recently. Under the Orphan Drug Act, the CT041 anti-claudin 18.2 product would be eligible for FDA support for clinical studies, special fee exemptions and reductions, and seven years of market exclusivity in the U.S.
“The IND clearance of CT041 by the FDA is of great significance to patients with advanced gastric and pancreatic cancer,” said Dr. Zonghai Li, founder, CEO, and CSO of CARsgen. “Despite the development of novel therapies, gastric and pancreatic adenocarcinomas remain incurable, and new treatment options are needed. Our goal is to continue the development of novel, safe and effective immunotherapies.”
Why Target Claudin18.2?
Besides the high annual incidence rate of gastric cancer in China, pancreatic cancer has over 450,000 new cases a year and is a malignancy with the highest unmet medical need. Targeting claudin18.2 positive by CAR T-cell treatment, CT041 kills two birds with one stone because claudins are heavily distributed throughout gastric, pancreatic, and lung tissues.
Claudins are a family of protein that maintains tight junctions and is responsible for the interchange of molecules between the cells. Malignant carcinogenesis triggers disruptions in tight junctions, as such exposing the subtype Claudin18.2 (a stomach specific-isoform) epitope on the surface of tumor cells. With this, Claudin18.2 endows targeting therapy with specificity. However, Claudin18.2 is typically hiding in gastric mucosa, making monoclonal antibodies challenging to navigate through normal tissues and access to the tumor spots. Hopefully, CT041 can overcome this challenge.
The Claudin 18.2 clinical study, which was just launched towards the end of September, is expected to receive primary endpoint results in 2020 and to be completed in 2035. The current study is an open-label, multicenter, Phase 1b clinical trial to evaluate autologous Claudin 18.2 CAR T-cell therapy’s safety and efficacy in patients with advanced gastric or pancreatic adenocarcinoma. The Phase 1 study is conducted by Professor Lin Shen at Beijing Cancer Hospital, Peking University in China.
The study is conducted in the form of 3+3 dose-escalation and expansion. A total of 30 patients are enrolled and must have their tumor tissues evaluated by Claudin18.2 immunohistochemistry (IHC) assay. After meeting all eligibility criteria, patients will undergo a leukapheresis procedure to collect autologous mononuclear cells for the manufacture of an investigational drug product, in this case, CT041. Later, the patients will receive preconditioning prior to CT041 infusion, as well as continuing for longer-term safety follow-up.
Editor: Rajaneesh K. Gopinath, Ph.D.
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