The phase 2 FIRCE-1 clinical trial investigating treatment with the CAR T-cell therapy firicabtagene autoleucel (firi-cel) in patients with large B-cell lymphoma (LBCL) whose disease relapsed or was refractory to CD19 CAR T-cell therapy has been discontinued by CARGO Therapeutics, according to a press release from the company.
Glossary
Complete response (CR): the absence of detectable tumor in a patient's body.
Immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS): a rare, potentially fatal complication that can occur after receiving CAR T-cell therapy which can lead to symptoms like fever, cytopenias, elevated ferritin levels, coagulopathy and organ dysfunction.
Overall response rate: the percentage of patients who have a complete or partial response to a treatment within a specific time frame.
Following a safety review of the FIRCE-1 trial, the company conducted an ad hoc analysis to assess the benefit-risk profile of firi-cel in the intended patient population. Data from 51 patients who had undergone at least one post-baseline scan showed an overall response rate of 77% and a complete response (CR) rate of 43%; however, the durability of CR at three months was limited to 18%.
The decision to discontinue treatment was made by the company, as findings indicate that firi-cel does not demonstrate a sufficiently competitive therapeutic advantage to justify continued development for this patient population.
“We are disappointed with these unexpected results from our Phase 2 study. 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,” Gina Chapman, president and chief executive officer of CARGO Therapeutics, said in the press release.
Furthermore, in terms of safety, 18% of patients experienced immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), a known toxicity linked to CAR T-cell therapies in other clinical studies. Notably, these events occurred at grade 3 (severe) or higher, with some cases escalating to grade 4 (life threatening or disabling) and grade 5 (fatal) serious events. Given these findings, the company has determined that the safety risks outweigh the potential benefits.
The open-label, multicenter, single-arm FIRCE-1 trial enrolled participants aged 18 years or older with histologically confirmed relapsed or refractory LBCL following their most recent line of therapy. In cohort 1, enrollment required prior treatment with a CD19-directed CAR T-cell therapy, cohort 2 consisted of patients who received a non-conforming dose of firi-cel that was determined to be safe for administration and cohort 3 included patients who had received at least two prior lines of therapy, one of which had to be a T cell–engaging bispecific antibody.
“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 concludes in the press release. “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. 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.”
Despite the discontinuation, in the press release, the company emphasized that it remains committed to advancing its pipeline, including the development of CRG-023, a tri-specific CAR T-cell therapy. The phase 1 dose escalation study for CRG-023 is on track to initiate in the second quarter of 2025.
The company notes that they intend to present an analysis of the phase 2 FIRCE-1 clinical trial during a medical conference in the future.
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