Docetaxel Plus Plinabulin vs Docetaxel Plus Placebo in Advanced/Metastatic Non-Squamous NSCLC After PD-1/PD-L1 Therapy and Platinum Chemotherapy (DUBLIN-4)

Participants with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have progressed following prior anti-PD-1/PD-L1 immunotherapy and platinum-based chemotherapy have limited treatment options and docetaxel remains a commonly used standard therapy in this setting. Plinabulin is a first-in-class small molecule with a distinct mechanism that may enhance anti-tumor activity and may mitigate chemotherapy-associated neutropenia. This study (DUBLIN-4) is designed to evaluate whether the addition of plinabulin to docetaxel improves clinical outcomes compared with docetaxel alone in this post-immunotherapy and post-platinum population without EGFR, ALK, ROS1, or RET alterations. This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study. Participants will be randomized in a 1:1 ratio to receive docetaxel in combination with plinabulin or matching placebo. Randomization will be stratified by geographic region (Asian countries vs Western countries), current line of therapy (2nd vs 3rd line), and prior progression-free survival duration on PD-1/PD-L1 inhibitor therapy (≥6 months vs \<6 months). Efficacy will be evaluated using standard radiographic tumor assessments and response criteria, with additional evaluation of clinically relevant outcomes in this treatment setting, including overall survival, progression-free survival, and objective response. Safety will be assessed throughout the study by monitoring adverse events, laboratory parameters, and other routine clinical assessments. The study also includes evaluation of patient-reported quality of life and the incidence of severe neutropenia as an important tolerability endpoint for docetaxel-based treatment. Participants who discontinue study treatment will enter follow-up, including a safety follow-up after treatment discontinuation and ongoing survival follow-up. Sparse pharmacokinetic samples will be collected to support population pharmacokinetic analyses of plinabulin.