CARGO Therapeutics to Discontinue Phase 2 Study of Firi-Cel in R/R LBCL

The phase 2 FIRCE-1 trial (NCT05972720) evaluating the CD22-directed CAR T-cell therapy firicabtagene autoleucel (firi-cel) for the treatment of patients with large B-cell lymphoma that is relapsed/refractory to a CD19-directed CAR T-cell therapy will be discontinued, according to an announcement from CARGO Therapeutics.1

The developer of firi-cel explained that data from FIRCE-1 did not support a competitive risk:benefit profile for the CAR T-cell therapy in this patient population. Findings from the study showed that evaluable patients (n = 51) experienced an overall response rate (ORR) of 77% and a complete response (CR) rate of 43%. However, the 3-month duration of CR rate was 18%.

Regarding safety, grade 3 or higher immune effector cell–associated hemophagocytic lymphohistiocytosis–like syndrome (IEC-HS) was reported in 18% of patients; this included grade 4 and 5 serious adverse effects.

Full data from FIRCE-1 will be submitted for presentation at an upcoming medical conference.

“We are disappointed with these unexpected results from our phase 2 study. Durability of CR is an important clinical goal for [patients with] LBCL who are relapsed/refractory to CD19[-directed] CAR T-cell therapy,” Gina Chapman, president and chief executive officer of CARGO Therapeutics, stated in a news release. “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.”

FIRCE-1 was an open-label, multicenter, single-arm study that enrolled patients at least 18 years of age with histologically confirmed LBCL that was relapsed/refractory following the last line of therapy.2 In cohort 1, prior treatment with a CD19-directed CAR T-cell therapy was required; those treated in cohort 3 needed to have received at least 2 prior lines of therapy, including a T cell–engaging bispecific antibody. Cohort 2 included patients who received a non-conforming dose of firi-cel that was deemed safe to administer.

Key inclusion criteria for all patients included at least 1 radiographically measurable lesion; an ECOG performance status of 0 or 1; and adequate hematologic, renal, and liver function.

Patients were excluded if they had a clinically significant concurrent illness; had active fungal, bacterial, viral, or other infections; or underwent prior allogeneic stem cell transplant or allogeneic cell therapy.

All treated patients underwent lymphodepleting chemotherapy with fludarabine and cyclophosphamide prior to receiving a single infusion of firi-cel.

Blinded independent central review–assessed ORR served as the trial’s primary end point. Secondary end points included ORR as assessed by investigators, CR rate, duration of response, duration of CR, progression-free survival, overall survival, and safety.

In lieu of the discontinuation of FIRCE-1, CARGO Therapeutics will shift its focus to the development of CRG-023, a tri-specific CAR T-cell therapy targeting CD19, CD20, and CD22, into a phase 1 escalation dose study.1

“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. 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,” Chapman added in the news release. “I’d also like to recognize and thank all of our employees at CARGO, including those being impacted by today’s decision, who have worked tirelessly on behalf of patients and made meaningful contributions to our Company’s mission.”

References

1. CARGO Therapeutics to discontinue FIRCE-1 phase 2 study of firi-cel; advances remaining programs while evaluating strategic options. News release. CARGO Therapeutics. January 29, 2025. Accessed January 30, 2025. https://investors.cargo-tx.com/news-releases/news-release-details/cargo-therapeutics-discontinue-firce-1-phase-2-study-firi-cel
2. A phase 2 study of firi-cel in patients with relapsed/​refractory large B-cell lymphoma (FIRCE-1). ClinicalTrials.gov. Updated December 17, 2024. Accessed January 30, 2025. https://clinicaltrials.gov/study/NCT05972720