WCLC 2025 - Posters & ePosters-P3.18.49 Efficacy and Safety of Tislelizumab Combined With Tofacitinib and Docetaxel for NSCLC After Failure of First-Line Immunotherapy

P3.18.49 Efficacy and Safety of Tislelizumab Combined With Tofacitinib and Docetaxel for NSCLC After Failure of First-Line Immunotherapy

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This prospective, single-arm, multicenter phase II study investigates the efficacy and safety of combining tislelizumab, tofacitinib, and docetaxel as a second-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) following failure of first-line immunotherapy. NSCLC accounts for about 85% of lung cancers and, despite advances with immune checkpoint inhibitors (ICIs), over 70% of patients experience disease progression within a year due to mechanisms like immunosuppressive tumor microenvironment and metabolic changes leading to resistance.<br /><br />Tislelizumab is a humanized anti-PD-1 monoclonal antibody designed to minimize Fcγ receptor binding that contributes to resistance. Tofacitinib, a Janus kinase (JAK) inhibitor, has shown promise in restoring exhausted T cell function and improving responses when combined with ICIs. Docetaxel is a standard chemotherapy agent used in NSCLC. Previous clinical trials combining JAK inhibition with ICIs have demonstrated encouraging response rates and survival benefits in related malignancies.<br /><br />In this study, approximately 39 eligible patients—aged 18-75, ECOG performance status 0-1, without EGFR, ROS1, or ALK mutations and with measurable lesions—receive daily 5 mg tofacitinib as pretreatment for 8 days, followed by every-three-week administration of 200 mg tislelizumab plus 75 mg/m² docetaxel until disease progression or unacceptable toxicity. Key exclusion criteria include significant cardiovascular disease, active infections, poor organ function, other malignancies, and pregnancy.<br /><br />The primary endpoint is objective response rate (ORR) by RECIST 1.1. Secondary endpoints include 6-month progression-free survival (PFS), disease control rate (DCR), duration of response (DoR), and overall survival (OS). Biomarker analyses from blood and tumor tissues will also be explored.<br /><br />Tumor assessments occur via CT or MRI, with adverse events monitored per CTCAE v5.0. Follow-up includes regular imaging and survival status evaluations post-treatment discontinuation.<br /><br />This study aims to establish a novel combined therapy approach targeting immune resistance mechanisms to improve outcomes in NSCLC patients who have failed first-line immunotherapy. Enrollment is ongoing.

Asset Subtitle

Wang Xie

Meta Tag

Speaker Wang Xie

Topic Clinical Trials in Progress

Keywords

non-small cell lung cancer

NSCLC

tislelizumab

tofacitinib

docetaxel

second-line treatment

immune checkpoint inhibitors

JAK inhibitor

phase II clinical trial

immune resistance