The FDA has lifted clinical holds on three of CARsgen Therapeutics' oncology cell therapies, paving the way for the resumption of clinical trials in the United States. The affected therapies include zevorcabtagene autoleucel (zevor-cel), a BCMA-directed CAR-T cell therapy for relapsed/refractory (r/r) multiple myeloma (MM); satricabtagene autoleucel (satri-cel), a Claudin18.2-directed CAR-T for gastric/pancreatic cancers; and CT071, a GPRC5D-directed CAR-T for r/r MM and r/r primary plasma cell leukemia. The removal of these holds marks a significant step forward for CARsgen as it seeks to advance its CAR-T therapies in the US market.
The clinical holds, initially implemented in December 2023, stemmed from chemistry, manufacturing, and controls (CMC)-related concerns identified during an FDA inspection of CARsgen’s manufacturing facility in Durham, North Carolina. CARsgen addressed these concerns through a comprehensive review and improvements to its current Good Manufacturing Practices (cGMP) at the facility.
Zevor-cel Approval in China
Notably, zevor-cel received approval from China’s National Medical Products Administration (NMPA) in March 2024 for treating adult patients with r/r MM who have progressed after at least three lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD). This approval was based on data from the phase 1/2 LUMMICAR STUDY 1 trial (NCT03975907), which demonstrated a 100% overall response rate (ORR) and a 78.6% complete response (CR)/stringent CR (sCR) rate in evaluable patients (n = 14) at a median follow-up of 37.7 months. All patients who achieved a CR/sCR also experienced minimal residual disease negativity.
Wenming Chen, MD, PhD, principal investigator of LUMMICAR STUDY 1, commented on the importance of this therapy for patients with r/r MM, stating, "In the realm of traditional treatments, the prognosis for patients dealing with relapsed or refractory multiple myeloma remains notably grim, given the limitations of available therapeutic alternatives...These individuals confront substantial unmet clinical needs, necessitating an expeditious adoption of an effective, safe, and convenient treatment modalities."
Satri-cel for Gastric and Pancreatic Cancers
CARsgen is also evaluating satri-cel in the ELIMYN18.2 clinical trial (NCT04404595) for heavily pretreated Claudin18.2 (CLDN18.2)-positive advanced gastric/gastroesophageal (GC/GEJ) or pancreatic cancer (PC). This phase 1b/2 trial assesses the safety and efficacy of satri-cel in patients whose disease has progressed or was unresponsive to at least two prior lines of systemic therapy for GC/GEJ or one prior line for PC.
Hong Ma, MD, Sr. Vice President of Clinical Development for Cancer Immunotherapy at CARsgen, highlighted the significance of the satri-cel program, noting, "This is worldwide the first CLDN18.2 program that has received multiple countries’ investigational new drug (IND) clearance...the program is also the first solid tumor CAR-T program that has received multiple designations from regulatory agencies."
