NCT07361484

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

A Global, Multicenter, Randomized, Double-blinded, Phase 3 Study of Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced or Metastatic Non-squamous Non-Small Cell Lung Cancer With EGFR, ALK, ROS, and RET Wild Type After Progressing on Prior Immunotherapy (Anti-PD-1/L1 Antibody) and Platinum-based Chemotherapy (DUBLIN-4)

• Status: Not Yet Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 442 (estimated)
• Sponsor: BeyondSpring Pharmaceuticals Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Non-Small Cell Lung Cancer
• Non-squamous Non-Small Cell Lung Cance

Interventions

Type	Name	Description
DRUG	Plinabulin	Plinabulin will be administered by IV infusion at 30 mg/m² over approximately 1 hour on Days 1 and 8 of each 21-day treatment cycle. On Day 1, plinabulin will be administered approximately 1 hour after completion of the docetaxel infusion.
DRUG	Docetaxel	Docetaxel will be administered by intravenous (IV) infusion at 75 mg/m² over approximately 1 hour on Day 1 of each 21-day treatment cycle.
DRUG	Placebo (matching plinabulin placebo)	Matching placebo will be administered by IV infusion over approximately 1 hour on Days 1 and 8 of each 21-day treatment cycle. On Day 1, placebo will be administered approximately 1 hour after completion of the docetaxel infusion.

Timeline

• Start date: 2026-06-01
• Primary completion: 2029-06-01
• Completion: 2029-12-01
• First posted: 2026-01-23
• Last updated: 2026-01-23

Regulatory

• FDA-regulated drug study