Phase 2 trial of lisocabtagene maraleucel for minimal residual disease in patients with large B-cell lymphoma.

Abstract

TPS7107 Background: Patients with relapsed/refractory large B-cell lymphoma (LBCL) have a poor prognosis. Identifying patients at high risk of recurrence after completion of first line (1L) treatment is crucial to enable early intervention with further treatments that may improve outcomes. Recent studies have shown that detectable minimal residual disease (MRD) by circulating tumor DNA (ctDNA) assay after 1L chemoimmunotherapy is prognostic for risk of recurrence. We hypothesize that lisocabtagene maraleucel (liso-cel) will eradicate the MRD in patients with LBCL who have detectable ctDNA at the end of 1L treatment will lead to improved long-term outcomes relative to historical results with liso-cel in second line treatment for patients with radiologically-detected disease. Methods: This is an open-label, phase 2, single-arm, multicenter, investigator-sponsored trial designed to evaluate the efficacy and safety of lisocabtagene maraleucel (liso-cel) in patients with LBCL who have achieved a response to 1L standard-of-care therapy but have detectable MRD. The trial will enroll 50 evaluable patients. Eligible participants are adults with LBCL, including DLBCL-NOS and HGBCL, who received 1L anthracycline-based chemoimmunotherapy (R-CHOP, DA-EPOCH-R, or polatuzumab-R-CHP) for six cycles, with or without an additional two cycles of rituximab, for previously untreated disease. Patients must have achieved a CR, or a PR with a negative biopsy or biopsy not feasible, and must demonstrate detectable MRD as assessed by the Foresight CLARITY ctDNA-MRD assay following completion of 1L therapy. The primary endpoint is event-free survival rate at 12 months, and secondary endpoints include rate of undetectable MRD. Correlative studies are designed to build a holistic model for understanding the tumor-intrinsic and immune features that contribute to response, as well as treatment-associated toxicities following liso-cel in patients with LBCL and detectable MD, a population at high risk of recurrence. Enrolment to the trial is planned at five centers in the US: MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, Fred Hutchinson Cancer Center, City of Hope and Massachusetts General Hospital (NCT07316010). Clinical trial information: NCT07316010 .