FDA Lifts Clinical Holds Placed on 3 CAR T-cell Therapy Trials
The FDA has lifted clinical holds on trials of zevor-cel, satri-cel, and CT071, and trials will now resume in the US.
The FDA has lifted the holds currently placed on clinical trials of zevor-cel, satri-cel, and CT071.1
These holds were initially placed on the trials due to concerns related to CMC following an inspection of the company’s manufacturing facility. These concerns were observed in Durham, North Carolina, last December.2
In the press release, it was noted that the company, CARsgen Therapeutics Holdings Limited, would conduct a comprehensive review and improvement on the Current Good Manufacturing Practice. The company planned to work closely with the FDA to address these findings.
The trials are now set to resume in the US.
About the CAR T-cell Products
Zevor-cel is an autologous CAR T-cell agent against BCMA being evaluated for the treatment of patients with relapsed/refractory multiple myeloma (RRMM).1 The phase 1b LUMMICAR study 1 (NCT03975907) conducted in China evaluated the agent in RRMM. Data from the study were presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition and included findings from 14 patients.3
The median age of those that were given a single infusion of zevor-cel was 54 years (range, 34-62). The dose was 100 × 106 CAR-positive (CAR+) T cells in 3 patients, and 150 × 106 CAR+ T cells as the recommended phase 2 dose in 11 patients.
The median survival follow-up duration was 37.7 months (range, 14.8-44.2) as of July 17, 2023. With this, the overall response rate was 100% (95% CI, 76.8%-100.0%), with 11 (78.6%) patients achieving complete response (CR) or stringent CR (sCR). There were 2 (14.3%) patients who achieved a very good partial response and 1 (7.1%) patient who had a partial response. All patients who achieved CR or better had minimal residual disease negativity.
For all patients, the median progression-free survival was 25.0 months (range, 14.9-not evaluable [NE]). This was 26.9 months (range, 15.5-NE) for those with sCR/CR. The median duration of response for all patients was 24.1 months (range, 14.0-NE) and 26.0 months (range, 14.6-NE) for patients with sCR/CR.
Further, at the data cutoff date, 5 patients had ongoing responses, 7 had progressed and were still in survival follow-up, and 2 had died at months 42.6 and 32.6, respectively. Both deaths were deemed unrelated to zevor-cel treatment.
Satri-cel is an autologous CAR T product against claudin 18.2 in solid tumors, including gastric/gastroesophageal junction cancer and pancreatic cancer.1 The agent is currently being evaluated in a phase 2 trial (NCT04404595). The study began enrollment in May 2023.
Additionally, satri-cel is being evaluated in conjunction with Moderna’s mRNA cancer vaccine as announced in August 2023.4
CT071 is an autologous CAR T product against G protein-coupled receptor class C group 5 member D (GPRC5D) for RRMM and primary plasma cell leukemia. In December 2023, the agent received investigational new drug application clearance from the FDA for the treatment of patients with RRMM or relapsed/refractory primary plasma cell leukemia.5
Currently, the agent is being assessed in this patient population within an investigator-initiated trial in China (NCT05838131). Experts are evaluating the safety and efficacy of CT071, and preliminary data has already shown an acceptable safety profile with preliminary efficacy.
