A phase II study of sitravatinib combined with tislelizumab plus docetaxel for acquired resistance to PD-(L)1 in patients with advanced/metastatic non-small cell lung cancer

In this phase ? study, 13 patients with stage III/? immune checkpoint inhibitors (ICIs) - acquired resistant non-small cell lung cancer (NSCLC) were treated with tislelizumab, sitravatinib, and docetaxel. The primary endpoint is a 6-month progression-free survival (PFS) rate. Although the target enrollment was not reached, the 6-month PFS rate among the enrolled patients was 58.9% (95% CI 0.234 - 0.825), with a median PFS of 7.589 months (95% CI 1.873 - 14.423) and a median OS of 17.150 months (95% CI 1.873 - not reached). The ORR was 58.3% (7 of 12 patients, 1 not evaluable), and the DCR was 100% (12 of 12 patients). Following treatment with sitravatinib, T-cell diversity (+0.435, p = 0.5) and the PSI of CD4? T cells tend to increase (+21.948, p = 0.8438), whereas the PSI of CD8+ T cells declines (-174.16, p = 0.0938). High CD4? T cells ?PSI (>40) was associated with a strong trend of longer PFS (14.400 vs 7.6 months, p = 0.0499). In conclusion, sitravatinib combination therapy demonstrated promising clinical benefit and manageable safety in NSCLC patients with acquired resistance to ICIs. Overall design: Peripheral blood samples were collected to perform TCR sequencing from patients at two time points: prior to the initiation of treatment (cycle 1, day 1 [C1D1], C1D1_Plasma group) and on the first day of the third treatment cycle (C3D1, C3D1_Plasma group). Additionally, tumor tissue samples (formalin-fixed, paraffin-embedded, FFPE) were also collected from patients in two reference groups: before immunotherapy (treatment-naïve group) and the ICI-resistant group (C1D1 ICI-PD group).