This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating docetaxel plus plinabulin versus docetaxel plus placebo in participants with advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without EGFR, ALK, ROS1, or RET alterations who have experienced disease progression after prior anti-PD-1/PD-L1 immunotherapy and platinum-based chemotherapy. Approximately 442 participants will be randomized 1:1 to receive docetaxel (75 mg/m² IV on Day 1 of each 21-day cycle) in combination with plinabulin (30 mg/m² IV on Days 1 and 8) or matching placebo. Treatment will continue until disease progression, unacceptable toxicity, death, withdrawal of consent, or sponsor/investigator decision. Tumor assessments will be performed regularly per RECIST v1.1, and participants will be followed for survival after treatment discontinuation. The primary objective is to compare overall survival between treatment arms; secondary objectives include evaluation of progression-free survival, objective response rate, duration of response, disease control, incidence of Grade 4 neutropenia, quality of life, and safety/tolerability.