First-line treatment with HDACis plus tislelizumab combined with chemotherapy in advanced NSCLC: a single-arm phase II study.

Background: Immune checkpoint inhibitors in combination with chemotherapy have been a common first-line treatment for non-small cell lung cancer (NSCLC), but they do not work for all patients. HDAC inhibitors (HDACis) may synergize with progressive disease (PD)-1 antibodies by inducing and activating cellular immunity. In this phase II study, we assessed the efficacy and tolerability of chidamide and tislelizumab in combination with chemotherapy in NSCLC patients.

Methods: This was a single-arm, prospective study. Driver-gene negative locally advanced and metastatic NSCLC patients without prior systemic treatment were enrolled. Patients received chidamide, tislelizumab, and chemotherapy for 4-6 cycles and were then maintained by tislelizumab and chidamide. The primary endpoint was objective response rate (ORR), and secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response, overall survival (OS) and safety.

Results: Twenty patients were enrolled in the study and most of them were PD-L1 1%-49% and PD-L1 < 1%. At the data cutoff, ORR was 80% (95% CI, 56.3-94.3), and DCR was 100%. The median follow-up was 23.4 months, the median PFS was 11.0 months (95% CI, 9.1-12.9m), and the median OS was 17.5 months (95% CI, 9.2-25.8m). Eleven patients (55.0%) had ≥ Grade 3 treatment-related adverse events (TRAEs). The most common ≥ Grade 3 TRAEs were leukopenia (25.0%) and neutropenia (20.0%). No patients died from treatment-related adverse events.

Conclusions: The combination of HDACi and tislelizumab with chemotherapy showed promising antitumor effects and manageable toxicity. More studies are needed to further confirm these results.

Clinicaltrials.gov Identifier: ChiCTR2000041542.