CARGO Therapeutics' Phase 1 Firi-cel CAR T-Cell Therapy Study Published in The Lancet

CARGO Therapeutics, Inc. recently shared promising data from a Phase 1 clinical study conducted by Stanford Medicine, evaluating firicabtagene autoleucel (firi-cel), a CD22 CAR T-cell therapy. The study focused on patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who had previously undergone CD19 CAR T-cell therapy without success. The findings, published in The Lancet, highlight the potential of firi-cel to address the unmet needs of these patients.

The study's results indicated that firi-cel could achieve significant overall response rates (ORR) and complete response (CR) rates, even in a challenging patient population. At a median follow-up of 23.3 months, the ORR was 68%, and the CR rate was 53% among the 38 patients treated. Remarkably, there were no notable differences in response rates across various patient subgroups. Specifically, 36% of patients who had previously been refractory to all prior therapies achieved complete responses.

For Dose Level 1 (DL1), the chosen dose for the Phase 2 study, the ORR and CR rates were 66% and 52%, respectively. The study also found that the estimated one- and two-year survival rates at DL1 were 57% and 52%, respectively. Importantly, firi-cel was well-tolerated with no incidents of grade 3 or higher cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or HLH-like syndrome.

Key characteristics of the Phase 1 patient population included a median age of 65 years, with half of the patients being over 65. Patients had undergone a median of four prior therapies, and a significant majority (68%) were at advanced disease stages (III or IV). Additionally, 84% had elevated lactate dehydrogenase levels, indicating a high tumor burden, and 97% had relapsed after previous CAR T-cell therapy.

Updated data presented at the 2024 European Hematology Association (EHA) Congress, with a median follow-up of 31.4 months, reinforced these findings. The ORR and CR rates remained consistent at 68% and 53%, respectively. For DL1 patients, the median overall survival was 25.7 months, and the estimated two-year survival stayed at 52%. Importantly, patients who achieved a complete response showed no additional relapses since the last data cut in November 2023.

Stanford Medicine's firi-cel received Breakthrough Therapy Designation from the FDA for treating adult patients with LBCL whose disease is R/R after CD19-directed CAR T-cell therapy. This designation underscores the potential impact of firi-cel in providing a new treatment option for this patient population.

Large B-cell lymphoma (LBCL) is a type of non-Hodgkin lymphoma that affects B lymphocytes, which are critical components of the immune system. It is an aggressive form of cancer that is most common in individuals over the age of 60 but can also occur in younger individuals.

Firicabtagene autoleucel (firi-cel) is an investigational therapy developed by CARGO Therapeutics. It utilizes autologous T-cells modified with a lentiviral vector to express a CD22-targeting chimeric antigen receptor (CAR). The therapy has shown promising results in Phase 1 trials, particularly for patients whose disease is refractory to CD19 CAR T-cell therapy.

CARGO Therapeutics is committed to advancing next-generation cell therapies for cancer patients. The company's strategies aim to address the limitations of current therapies, including safety concerns, limited durability, and supply issues. CARGO's flagship program, firi-cel, is currently being evaluated in a potentially pivotal Phase 2 study for patients with LBCL. Beyond this, the company is leveraging its proprietary platform technologies to develop a pipeline of innovative therapies designed to enhance CAR T-cell persistence, trafficking, and resistance to tumor mechanisms.