Cargo Therapeutics Halts CAR-T Program Amid Safety Concerns and Efficacy Issues

Cargo Therapeutics, a biopharmaceutical company focused on developing CAR-T cell therapies, announced a significant setback in its lead program, resulting in a major restructuring of the company. The decision comes after an ad-hoc analysis of their phase 2 trial revealed disappointing efficacy and serious safety concerns.

Firi-cel Program Terminated Following Underwhelming Trial Results

Cargo's lead candidate, firicabtagene autoleucel (firi-cel), an autologous CD22 CAR-T cell therapy, was being evaluated in a phase 2 trial for patients with large B-cell lymphoma (LBCL) whose disease had relapsed or was unresponsive to CD19 CAR-T therapy. The trial, which had dosed 71 patients, was initially viewed as potentially pivotal for the company's future.

However, an interim analysis of data from 51 patients painted a grim picture:

• Overall response (OR) rate: 77%
• Complete response (CR) rate: 43%
• Three-month durability of CR: 18%

The durability of complete response, a critical clinical endpoint for LBCL patients who are refractory or relapsed to CD19 CAR-T cell therapy, fell far short of expectations.

Safety Concerns Amplify Decision to Discontinue Firi-cel

Compounding the efficacy issues, the trial revealed significant safety concerns:

• 18% of patients developed grade 3 or higher immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS)
• Grade 4 and 5 serious adverse events were reported, with grade 5 indicating patient death

The high occurrence and severity of IEC-HS, a known toxicity associated with CAR-T cell therapy, further contributed to the company's decision to terminate the firi-cel program.

Gina Chapman, CEO of Cargo Therapeutics, expressed disappointment with the unexpected results, stating, "Combined with a higher-than-expected occurrence and severity of IEC-HS, the data generated so far does not meet our expectations of a competitive benefit-risk profile for patients in the context of available treatment options."

Corporate Restructuring and Financial Impact

In response to these developments, Cargo Therapeutics has announced a significant corporate restructuring:

• 50% reduction in workforce
• Shift in focus to CRG-023, a trispecific CAR-T therapy entering phase 1 dose-escalation trials
• Extension of cash runway into mid-2028, with $368.1 million on hand at the start of 2025

The news had an immediate and severe impact on Cargo's stock price, which plummeted 75% in premarket trading, falling from $13.19 to $3.31.

William Blair analysts expressed surprise at the trial's outcome, noting the contrast with promising phase 1 results. They speculated that the challenging patient population, who had previously undergone CAR-T treatment, might have contributed to the lack of durability due to higher proportions of terminal effector memory cells or immunosuppressive T regulatory cells in their CAR-T products.

As Cargo Therapeutics navigates this setback, the company will continue to evaluate its strategic options while advancing its remaining pipeline candidates. The discontinuation of the firi-cel program serves as a stark reminder of the challenges inherent in developing novel cell therapies, particularly for heavily pretreated patient populations.