CARGO Therapeutics has discontinued its Phase 2 FIRCE-1 clinical trial evaluating firicabtagene autoleucel (firi-cel) for patients with relapsed or refractory large B-cell lymphoma (LBCL) following prior CD19-directed CAR T-cell therapy. The decision was based on an ad hoc analysis that revealed a lack of competitive benefit-risk profile due to poor durability of response and safety concerns.
The open-label, multicenter, single-arm FIRCE-1 trial enrolled patients with histologically confirmed LBCL who had relapsed or were refractory after their last line of therapy. Efficacy data from 51 evaluable patients showed an overall response rate (ORR) of 77% and a complete response (CR) rate of 43%. However, the duration of CR at three months was only 18%.
Safety Concerns
Safety data indicated that 18% of patients experienced grade 3 or higher immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), a known complication of CAR T-cell therapy. These events included grade 4 and grade 5 serious adverse events, raising significant safety concerns.
"We are disappointed with these unexpected results from our Phase 2 study," said Gina Chapman, president and chief executive officer of CARGO Therapeutics. "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. Therefore, we believe it is in the best interest of both patients and shareholders to discontinue the study."
Strategic Shift
In light of the discontinuation, CARGO Therapeutics will shift its focus to advancing CRG-023, a tri-specific CAR T-cell therapy targeting CD19, CD20, and CD22, into a Phase 1 dose escalation study. The company also plans to continue developing its novel allogeneic platform.
To preserve cash, CARGO Therapeutics is implementing a workforce reduction of approximately 50%. The company expects its cash runway to extend into mid-2028, with preliminary cash, cash equivalents, and marketable securities of $368.1 million as of December 31, 2024.
"While we continue to advance CRG-023 into the clinic this year and progress our novel allogeneic platform, we will also evaluate our strategic options," Chapman added. "We are grateful for the patients, caregivers and families who were involved in the FIRCE-1 study, as well as the investigators who partnered closely with us and with whom we look forward to continuing to collaborate."
CARGO Therapeutics intends to present a full analysis of the FIRCE-1 Phase 2 study at an upcoming medical conference.
