FDA Lifts Clinical Holds on CARsgen's CAR-T Therapy Trials
Key Insights
The FDA has lifted clinical holds on CARsgen Therapeutics (search)' trials for zevor-cel, satri-cel, and CT071, allowing the resumption of these studies in the US.
The holds were initiated due to CMC concerns identified during an inspection of CARsgen's manufacturing facility in Durham, North Carolina.
Zevor-cel targets BCMA (search) for relapsed/refractory multiple myeloma (search), satri-cel targets claudin 18.2 (search) in solid tumors, and CT071 targets GPRC5D (search) for RRMM and primary plasma cell leukemia (search).
The FDA has lifted the clinical holds placed on three CAR-T cell therapy trials by CARsgen Therapeutics (search), paving the way for their resumption in the United States. The trials involve zevor-cel, satri-cel, and CT071, all autologous CAR-T cell therapies targeting different cancers.
The clinical holds were initially implemented following concerns related to Chemistry, Manufacturing, and Controls (CMC) observed during an FDA inspection of CARsgen's manufacturing facility in Durham, North Carolina, in December 2023. CARsgen has since conducted a comprehensive review and improvement of its Current Good Manufacturing Practice (CGMP) and worked closely with the FDA to address the identified issues.
Zevor-cel (CT041) for Relapsed/Refractory Multiple Myeloma
Zevor-cel, also known as CT041, is an autologous CAR-T cell therapy targeting B-cell maturation antigen (BCMA (search)), a protein highly expressed on multiple myeloma (search) cells. It is being evaluated for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). A phase 1b study (LUMMICAR STUDY 1, NCT03975907) conducted in China, evaluated zevor-cel in RRMM. Data presented at the 2023 ASH Annual Meeting & Exposition from 14 patients showed a 100% overall response rate (95% CI, 76.8%-100.0%), with 78.6% achieving complete response (CR) or stringent CR (sCR). The median progression-free survival was 25.0 months (range, 14.9-NE) for all patients and 26.9 months (range, 15.5-NE) for those with sCR/CR.
Satri-cel for Solid Tumors
Satri-cel is an autologous CAR-T cell product targeting claudin 18.2 (search), a protein expressed in various solid tumors, including gastric/gastroesophageal junction cancer (search) and pancreatic cancer (search). It is currently being evaluated in a phase 2 trial (NCT04404595), which began enrollment in May 2023. CARsgen is also exploring satri-cel in combination with Moderna’s mRNA cancer vaccine.
CT071 for Relapsed/Refractory Multiple Myeloma and Primary Plasma Cell Leukemia
CT071 is an autologous CAR-T cell product targeting G protein-coupled receptor class C group 5 member D (GPRC5D (search)), another target for RRMM and primary plasma cell leukemia (search). In December 2023, CT071 received investigational new drug (IND) application clearance from the FDA. An investigator-initiated trial in China (NCT05838131) is currently assessing the safety and efficacy of CT071 in this patient population, with preliminary data showing an acceptable safety profile and promising efficacy.