Med (New York, N.Y.) · 2025
Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers.
СтатьяКлиническое исследование I фазыПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Lin Steven H, Subbiah Vivek, Neri Shinya, Cohen Evan N, Li Ziyi, Lu Yingjuan June, Son Ye Lin, Lyu Yue, Braun Chen, Gao Hui, Jayachandran Gitanjali, Sharma Amrish, Ye Rui, Fang Penny, Li Nan, Karp Daniel, Hong David, Rodon Jordi, Yu Hao, Peng Jing, Lloyd G Kenneth, Tonra James R, Reuben James M, Huang Lan, Fu Siqing
Аннотация
BACKGROUND: Plinabulin exerts immunomodulatory activity through guanine nucleotide exchange factor (GEF)-H1 release from depolymerizing tubulin in the cytoskeleton, leading to dendritic cell (DC) activation. Preclinical studies demonstrated that irradiation potentiates plinabulin-induced DC maturation and, when combined with immune checkpoint inhibitors (ICIs), triggers an abscopal antitumor response via increased tumor-infiltrating DCs and T cells.
METHODS: A phase 1 translational study (NCT04902040) of plinabulin plus ICIs after radiation therapy (RT) initiation was conducted in ICI-relapsed/refractory cancers with primary (safety, tolerability, and objective tumor response rate) and secondary (disease control rate [DCR]) endpoints.
FINDINGS: This triple regimen was safe and achieved a DCR of 54% (3/13 partial response [PR] and 4/13 stable disease [SD]) in mostly heavily pretreated patients. Responding tumors included non-small cell lung cancer (2/2 PR + SD), head-and-neck squamous cell carcinoma (2/3 PR + SD), and Hodgkin's lymphoma (2/2 PR in patients after 12 or 16 prior lines of therapy). PR + SD patients had significantly higher GEF-H1 immune-activation scores in peripheral blood and intratumorally at pretreatment/baseline and DC activation/T cell clonal expansion post-treatment compared with progressive disease patients.
CONCLUSIONS: These preliminary results provide a rationale for testing RT/plinabulin/ICI combination in future post-ICI-failure confirmatory trials.
FUNDING: This study was funded by BeyondSpring Pharmaceuticals, Inc.
METHODS: A phase 1 translational study (NCT04902040) of plinabulin plus ICIs after radiation therapy (RT) initiation was conducted in ICI-relapsed/refractory cancers with primary (safety, tolerability, and objective tumor response rate) and secondary (disease control rate [DCR]) endpoints.
FINDINGS: This triple regimen was safe and achieved a DCR of 54% (3/13 partial response [PR] and 4/13 stable disease [SD]) in mostly heavily pretreated patients. Responding tumors included non-small cell lung cancer (2/2 PR + SD), head-and-neck squamous cell carcinoma (2/3 PR + SD), and Hodgkin's lymphoma (2/2 PR in patients after 12 or 16 prior lines of therapy). PR + SD patients had significantly higher GEF-H1 immune-activation scores in peripheral blood and intratumorally at pretreatment/baseline and DC activation/T cell clonal expansion post-treatment compared with progressive disease patients.
CONCLUSIONS: These preliminary results provide a rationale for testing RT/plinabulin/ICI combination in future post-ICI-failure confirmatory trials.
FUNDING: This study was funded by BeyondSpring Pharmaceuticals, Inc.