Selinexor Combined with Tislelizumab in Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma (R/R ENKTL): Preliminary Results of Arm C, from a Multicenter, Single-Arm, Phase I/II Study, Touch

Field: Medicine (Health Sciences)

Introduction: ENKTL is a rare subtype of mature T and NK/T cell lymphoma characterized by a highly aggressive clinical course and resistance to traditional chemotherapy. The prognosis remains extremely poor for R/R ENKTL patients (pts) who fail L-Aspariginase (L-Asp) based regimens, highlighting the need for novel approaches. Check point inhibitors (CPI) including Tislelizumab (Tis) reported preliminary clinical activity in R/R ENKTL in several clinical trials. Selinexor (Sel), a novel XPO1 inhibitor, has demonstrated preclinical synergistic effects when combined with a CPI. This report aims to update the cumulative data of Arm C from Touch study (Sel plus Tis in treating R/R ENKTL). Method: Arm C was designed to evaluate the safety, tolerability, preliminary efficacy of Sel plus Tis in R/R ENKTL. Pts who received at least one prior treatment containing L-Asp were enrolled. Sel was administered orally at dose level of 40 mg QW or 60 mg QW on Days 1, 8, and 15 of each 21-day cycle. Tis was administered at a fixed dose of 200 mg every 3 weeks on Day 1. Efficacy was evaluated per Lyric 2016 by investigators. Results: As of 18 May 2024, 17 R/R ENKTL pts were enrolled in Arm C [Sel 40mg (n=3); Sel 60mg (n=14)]. At study entry, the median age was 51 years (range 20-80); Nine males and 8 females; 10 (58.8%) had stage III/IV disease; 11 (64.7%) pts had PINK score ≥2 and 9 (52.9%) pts were circular EBV-DNA positive. The median number of prior systemic treatment lines was 2 (range 1-5); sixteen pts previously exposed to both L-Asp and CPIs including 8 pts who had received prior Tis; eleven (64.7%) pts were refractory to their last-line therapy. All pts experienced at least one treatment-emergent adverse event (TEAE). The most common TEAEs were anemia, neutropenia (82.4%, respectively), asthenia (76.5%), nausea (64.7%), vomiting (58.8%), decreased appetite, weight loss (52.9%, respectively), thrombocytopenia, lymphocytopenia (47.1%, respectively), proteinuria (41.2%), pneumonia, ALT increased, hypothyroidism (29.4%, respectively). Ten pts (58.8%) experienced Grade≥3 TEAEs. TESAEs occurred in 4 pts (23.5%) with only 1 (sepsis) considered treatment related. No pt discontinued due to TEAEs. Three pts died due to disease progression before the cut-off date. Most of toxicities were manageable by dose modification and supportive care. In intent-to-treat (ITT) population, the ORR was 70.6% (12/17), the DCR was 76.5% (13/17) and CR rate was 41.2% (7/17). One pt was considered efficacy non-evaluable due to early withdraw for personal reason. Of 16 CPIs exposed pts, the ORR achieved 75% (12/16) including 7 CRs and 5 PRs. In Sel 60mg cohort, 6 CRs and 5 PRs were observed. At a median follow-up time of 10.48 months (range 4.7-17.3), the median PFS of ITTs were 6.7 months (95% CI 2.89, NE). The median DOR and OS were not reached. The estimated 6-month response rate was 56.6% (95% CI 19.7, 81.9) and the estimated 12-month OS rate was 81.9% (95% CI 53.8, 93.8). In Sel 60mg cohort, the median PFS, DOR and OS were not reached. Conclusion: The chemo-free regimen, Sel plus Tis, demonstrated a favorable response rate and manageable safety profile in R/R ENKTL. This approach may probably reverse the drug resistance in population refractory to early lines treatment with CPIs. Long-term follow-up and larger clinical trials are still needed in the future.