ABSTRACT In this Phase II study, 13 patients with stage IIIB/IV non‐small cell lung cancer with acquired resistance to immune checkpoint inhibitors were treated with tislelizumab, sitravatinib, and docetaxel. The efficacy and safety were evaluated. The combination treatment achieved median progression‐free survival of 7.6 months, median overall survival of 17.2 months, an objective response rate of 58.3% (1 not evaluable), and a disease control rate of 100%. Grade ≥ 3 treatment‐related adverse events were primarily neutropenia and leukopenia. Exploratory analyses showed a trend toward increased T cell receptor (TCR) diversity following treatment. High pre‐treatment CD8 + T cell polyfunctional strength index (PSI) showed a trend toward association with early treatment response and deeper tumor shrinkage, while CD8 + PSI decreased post‐therapy in responders, although not significantly. Larger changes in CD4 + T cell PSI were associated with longer PFS. Although these data indicate clinical benefit and immunologic correlates, the limited sample size precludes definitive conclusions. Furthermore, the observed changes in TCR and PSI dynamics are preliminary, hypothesis‐generating, and may provide insights for optimizing therapeutic strategies. However, validation via large‐scale, randomized controlled clinical trials remains warranted. Trial registration : Chictr.org.cn, ChiCTR2200065547. Registered in 2022‐11‐08, https://www.chictr.org.cn/showproj.html?proj=183439 .
Li et al. (Mon,) studied this question.
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