FDA Grants Orphan Drug Designation to Investigational CAR T-Cell Agent in Gastric/GEJ Cancer

The FDA granted Orphan Drug designation to the humanized anti-claudin18.2 autologous chimeric antigen receptor (CAR) T-cell agent, CT041, for the treatment of patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma, according to a press release from CARsgen Therapeutics Co., Ltd, the developer of CT041.

CT041 was the first drug of its kind to receive an Investigational New Drug (IND) clearance from the FDA as well as from the National Medical Products Administration in China.

“The orphan drug designation of CT041 by the FDA is of great significance to patients with advanced gastric cancer," Zonghai Li, MD, PhD, founder, CEO, and chief scientific officer of CARsgen, said in a statement.

In patients with gastric and GEJ cancers, CT041 being investigated in a phase 1b clinical trial (NCT04404595) to determine its safety and efficacy. The study will include approximately 30 patients who will be assessed for the coprimary end points of incidence of treatment-related adverse events and the maximum tolerated dose of CT041. The secondary end points of the open-label, multicenter study include time to progression, duration of response, disease control rate, progression-free survival, and overall survival.

All patients enrolled in the study will be aged 18 to 80 years with histologically or cytologically confirmed stomach or GEJ cancer or pancreatic adenocarcinoma with claudin18.2-positive (CLDN18.2) tumor expression identified with a CLDN18.2 immunohistochemistry assay and be intolerant to systemic therapy. In addition, patients are required to have a life expectancy of at least 12 weeks; a minimum of 1 measurable lesion per RECIST v1.1 criteria; an ECOG performance status of 0 to 1; and adequate complete blood counts, renal, and hepatic functions.

Patients are not eligible to be treated with CT041 in the study if they had anticancer treatment approximately 2 weeks prior to leukapheresis or approximately 3 weeks before preconditioning therapy, received prior cellular therapy, had surgery less than 1 week prior to leukapheresis or 3 weeks before preconditioning, have central nervous system metastatic disease, leptomeningeal disease, or cord compression, require anticoagulant therapy such as warfarin or heparin or long-term antiplatelet therapy, had adverse events from previous treatment that have not recovered, or had other disease or infections that may interfere with study treatment.

The study will follow a 2-part 3 + 3 design. In part A, the dosing of CT041 will be escalated to determine the maximum tolerated dose of the drug. In part B, an expansion cohort will be brought in to further assess the safety and efficacy of the agent. Once the CAR T-cell agent is manufactured for all patients in study, the patients receive preconditioning prior to CT041 infusion. All patients in the study will be followed long term for a safety analysis following the efficacy analysis.

_Reference:

_{CARsgen Therapeutics granted Orphan Drug Designation by the US FDA for CT041 CLDN18.2 CAR-T cells for the treatment of gastric and gastroesophageal junction cancers. News release. CARsgen Therapeutics Co., Ltd. October 5, 2020. Accessed October 6, 2020. https://yhoo.it/3iCaCBB​}