Selinexor plus tislelizumab in patients with relapsed/refractory natural killer/T-cell lymphoma after failure of PD-1 blockade: the phase 1b TOUCH trial

BACKGROUND: Relapsed or refractory extranodal natural killer/T-cell lymphoma (R/R NKTCL) remains a highly lethal disease, particularly after failure of PD-1 blockade-based therapy. Preclinical data suggest that inhibition of exportin-1 (XPO1) may enhance antitumor immunity and synergize with PD-1 blockade. PATIENTS AND METHODS: We conducted a multicenter, open-label phase 1b study (TOUCH, Arm C) evaluating selinexor plus tislelizumab in patients with R/R NKTCL previously treated with L-asparaginase-containing regimens. A standard 3 + 3 dose-escalation design was followed by dose expansion. RESULTS: Seventeen patients were enrolled; 16 had prior checkpoint inhibitor (CPI) exposure and comprised the efficacy population. No dose-limiting toxicities were observed. Grade ≥3 treatment-emergent adverse events occurred in 52.9% of patients; hematologic toxicities were the most common. Among patients with prior CPI exposure, the overall response rate was 75.0% (12/16), including complete responses in 43.8% (7/16). Responses were observed in patients with primary CPI-refractory disease. With a median follow-up of 21.7 months, median progression-free survival was 6.1 months (95% CI, 2.9-not estimable), and the 2-year progression-free survival rate was 37.5%. Median overall survival was not reached; the 2-year overall survival rate was 73.4%. CONCLUSION: Selinexor plus tislelizumab demonstrated manageable toxicity and substantial activity in patients with relapsed/refractory NKTCL previously treated with CPI, supporting further evaluation of nuclear export inhibition as a strategy to re-engage antitumor immunity after failure of PD-1 blockade. CLINICALTRIALS.GOV IDENTIFIER: NCT04425070.