First-line HDACi plus tislelizumab combined with chemotherapy in advanced NSCLC.

Abstract

e21100 Background: Resistance to ICIs remains a challenge. HDAC inhibitors may synergize with PD-1 antibodies by inducing and activating NK cell and cytotoxic T cell (CTL) -mediated cellular immunity. Tislelizumab is an anti-PD-1 mAb approved for the treatment of NSCLC. Chidamide, a subtype-selective HDACi. This Phase 2 study assessed antitumor activity and tolerability of chidamide and tislelizumab combined with chemotherapy in advanced NSCLC. Methods: This was an open-label, prospective study. Patients with histologically or cytologically confirmed NSCLC (stage IIIB-IV) without prior systemic treatment was enrolled. EGFR/ALK mutation or fusion and symptomatic brain metastases were ineligible. Patients received chidamide 20 mg twice weekly orally, tislelizumab 200 mg Q3W intravenously, chemotherapy Q3W(≤4~6 cycles) until unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was ORR. Secondary endpoints include DCR、PFS、OS and safety. Tumor response was assessed using RECIST v1.1. Results: 20 patients were enrolled in the study. At the data cut-off February 10, 2023, the median age was 63.5 years (range: 49-75) and all patients were male 90% of who with smoking history. Most patients were stage IV(95%) .40% of the patients whose PD-L1 expression was positive (PD-L1 TPS≥1%) . The confirmed ORR was 75%(95%CI:56.0-94.0) and 1 patient was evaluated as CR. The DCR was 100%. The median follow-up was 13.1 months, median PFS was 11.7 months (95%CI:7.4m-16.0m) and 1-year PFS rate was 55.6% (95%CI:43.7%-67.5%). Median OS was not reached. 11 patients (55.0%) had ≥ Grade 3 TRAEs. The most common ≥Grade 3 TRAEs were leukopenia (25.0%), neutropenia (20.0%) and thrombocytopenia (15%). Conclusions: Adding HDACi(Chidamide) plus Tislelizumab combined with chemotherapy showed encouraging antitumor activity and a favorable safety profile as first-line therapy for advanced NSCLC. Clinical trial information: ChiCTR2000041542 . [Table: see text]