Combination of mitoxantrone hydrochloride liposome with tislelizumab in patients with relapsed or refractory NK/T cell lymphoma: A phase Ib/II study.

7055 Background: Natural killer/T-cell lymphoma (NKTCL) is a unique subtype of non-Hodgkin lymphoma with aggressive disease course. Mitoxantrone hydrochloride liposome (Lipo-MIT) is a nano-drug that has been approved for relapsed/refractory (r/r) PTCL, and has shown certain efficacy and safety in a pivotal phase Ⅱ study (Cancer. 2025, e35672). Tislelizumab is a humanized immunoglobulin G4 variant monoclonal antibody against PD-1. This study aims to investigate the safety and efficacy of combining Lipo-MIT with tislelizumab in patients (pts) with r/r NKTCL. Methods: Pts with r/r NKTCL and failed asparaginase-based therapy were recruited in this single-arm, multicenter phase Ib/Ⅱ study (NCT05464433). Phase Ib was 3+3 dose escalation design with two dose levels of Lipo-MIT (16 mg/m 2 and 20 mg/m 2 , d1) plus tislelizumab 200 mg (d1, Q4W) induction therapy for up to 6 cycles, then tislelizumab 200 mg (Q3W) maintenance therapy for up to 1 year. Phase II was conducted at the recommended phase II dose (RP2D). The primary endpoints were safety and tolerability, and determination of the maximum tolerated dose (or RP2D) of Lipo-MIT in phase Ib, and the overall response rate (ORR) of phase II. Results: As of the data cut-off on January 24, 2025, a total of 40 eligible pts were enrolled (phase Ib, n=6 and phase II, n=34). The median age was 46.5 (range 22-73) years. Among the pts, 62.5% had stage III or IV and 87.5% had nasal type NKTCL. No dose-limiting toxicities (DLT) were observed in the phase Ib study, and the RP2D of Lipo-MIT was determined to be 20 mg/m 2 . The ORR and DCR were all of 100.0% (6/6, 95% CI 60.7%-100.0%) and the CR rate was 66.7% (4/6, 95% CI 27.1%-93.7%) in phase Ib. In the ongoing phase II stage, 30 pts were evaluable for efficacy. The ORR, DCR and CR rate were 70.0% (21/30, 95% CI 50.6%-85.3%), 76.7% (23/30, 95% CI 57.7%-90.1%) and 46.7% (14/30, 95% CI 28.3%-65.7%), respectively. Overall, combining data from phase Ib and phase II, the ORR was 75.0% (27/36, 95% CI 57.8%-87.9%) and the CR rate was 50.0 (18/36, 95% CI 32.9%-67.1%). Among the 15 pts who had not used PD-1 before, CR rate was 66.7% and ORR reached 80.0%. The median PFS and OS will be reported with longer follow-up. The most common grade 3/4 treatment-related adverse events (TRAEs) included leucopenia (37.5%), neutropenia (30.0%) and decreased lymphocyte count (27.5%). Notably, no cardiac events occurred during the study. Conclusions: Lipo-MIT in combination with tislelizumab demonstrated an encouraging efficacy in r/r NKTCL pts with a manageable safety profile. Clinical trial information: NCT05464433 .