Cargo Therapeutics is lightening its load, jettisoning 50% of its employees along with the CAR-T company’s lead candidate in the wake of weak durability and serious side effects.
The drug in question, called firicabtagene autoleucel or firi-cel, is an autologous CD22 CAR-T cell therapy that had been undergoing a phase 2 trial in patients with large B-cell lymphoma whose disease relapsed or didn’t respond to CD19 CAR T therapy.
As recently as three weeks ago, the outlook had seemed positive for firi-cel, with Cargo reporting that 71 patients had been dosed in the trial. The biotech was “on track” to report an interim analysis of the data in the first half of the year for what it described as the “potentially pivotal” study.
Now, it appears the study has indeed been pivotal to Cargo—for all the wrong reasons. The biotech announced yesterday that it had conducted an “ad-hoc analysis” of the trial “prompted by recent safety events.” While this review of data from 51 patients had revealed an overall response (OR) rate of 77% and a complete response (CR) rate of 43%, the durability of this CR rate at the three-month mark was just 18%.
What’s more, 18% of patients developed immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS)—a toxicity associated with CAR T-cell therapy—that was grade 3 or higher. These included grade 4 and grade 5 serious adverse events, with grade 5 meaning a death, although Cargo didn't say how many patients had suffered this result.
Having judged that the data “do not support a competitive benefit-risk profile for patients,” Cargo has decided to scrap the firi-cel program. The company’s new focus will be on taking its trispecific CAR-T CRG-023 into a phase 1 dose-escalation trial.
Having entered the new year with $368.1 million to hand, the biotech said it will halve its head count in order to extend its cash runway into mid-2028 while it continues to “evaluate its strategic options.”
“We are disappointed with these unexpected results from our phase 2 study,” Cargo CEO Gina Chapman said in the release. “Durability of complete response is an important clinical goal for LBCL patients who are R/R to CD19 CAR T-cell therapy. 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.”
Cargo launched in 2022 with $200 million before going public the following year with a $281 million IPO. The company’s stock crashed in the wake of the firi-cel news, losing 75% of its value in premarket trading Thursday to sit at $3.31 compared to a Wednesday closing price of $13.19.
William Blair analysts said they were disappointed that firi-cel had been unable to deliver on the promise shown in a phase 1 trial, when the median PFS and OS had not been reached in the 20 patients who achieved a CR.
“In addition, we recognize this was a very sick patient population who had already previously undergone CAR-T treatment and therefore may have had higher proportions of terminal effector memory cells or immunosuppressive T regulatory cells in their CAR-T products, which could have contributed to the lack of durability,” the analysts wrote in a Jan. 30 note. “We are also surprised by the rate of high grade IEC-HS, as this was previously only observed at higher doses or with a product manufactured with different potency parameters.”