Plinabulin Receives FDA Fast Track Designation in Post-ICI NSCLC

The FDA has granted fast track designation to plinabulin, an investigational small-molecule GEF-H1 agonist, in combination with docetaxel for the treatment of patients with advanced or metastatic non-squamous non–small cell lung cancer (NSCLC) without actionable genomic alterations.¹

The designation specifically applies to patients in the second- or third-line setting after progression following prior anti–PD-(L)1 therapy and platinum-based chemotherapy, aligning with the population being evaluated in the global phase 3 DUBLIN-4 trial (NCT07361484).

Fast track designation is intended to facilitate the development and review of therapies for serious conditions with unmet medical needs. The designation provides opportunities for more frequent interactions with the FDA during development and may allow for rolling review of a future regulatory application.

“We believe the FDA [f]ast [f]rack designation, an FDA-aligned global [p]hase 3 strategy…would meaningfully strengthen our ability to advance plinabulin and DUBLIN-4 toward the trial’s next major clinical milestone—the prespecified interim analysis at 221 [progression-free survival; PFS] events,” said Min Qiu, CEO of BeyondSpring Pharmaceuticals, in a news release. “Fast [t]rack designation underscores the significant unmet medical need for the DUBLIN-4 patient population in patients [with] NSCLC whose disease has progressed following [immune checkpoint inhibitors] and without [actionable genomic alterations], with limited options and docetaxel as the standard of care.”

About DUBLIN-4

DUBLIN-4 is a randomized, double-blind, placebo-controlled, global phase 3 study evaluating plinabulin plus docetaxel vs docetaxel alone in patients with advanced or metastatic non-squamous NSCLC without actionable genomic alterations including EGFR, ALK, ROS1, or RET alterations following progression on immune checkpoint inhibitor therapy and chemotherapy.² Approximately 442 patients are planned for enrollment and will be randomized 1:1 between the treatment groups.

The primary end point is overall survival (OS), with PFS and objective response rate (ORR) serving as secondary end points. The study includes a prespecified interim analysis after 221 PFS events. The trial population is expected to include approximately 221 patients enrolled at sites in China, with the remainder enrolled through the broader global program, including sites in the United States and other regions.

In DUBLIN-4, plinabulin is administered at 30 mg/m² intravenously on days 1 and 8 of each 21-day cycle, while docetaxel is administered at 75 mg/m² intravenously on day 1.

Prior Findings Support Continued Evaluation

The DUBLIN-4 study builds on findings from the phase 3 DUBLIN-3 trial (NCT02504489), which evaluated plinabulin plus docetaxel vs docetaxel alone in patients with advanced NSCLC who had received prior systemic therapy.

According to findings from DUBLIN-3 published in The Lancet Respiratory Medicine, among 332 patients with non-squamous NSCLC, the combination was associated with longer OS compared with docetaxel alone, with a hazard ratio of 0.72 (P =.0078). Improvements in PFS and ORR were also observed, along with a reduction in grade 4 neutropenia with the combination.³

The planned interim analysis of DUBLIN-4 will provide prospective data on the efficacy of plinabulin plus docetaxel in patients with advanced or metastatic non-squamous NSCLC following progression on ICI-based therapy.

REFERENCES

1. BeyondSpring Announces FDA Fast Track Designation for Plinabulin in Post-ICI Non-Squamous NSCLC and Strategic Transaction to Advance Global Phase 3 DUBLIN-4 Trial Toward Planned Interim Analysis. News release. BeyondSpring Pharmaceuticals. September 29, 2026. Accessed September 30, 2026. https://tinyurl.com/y2tzr8bu

2. Docetaxel Plus Plinabulin vs Docetaxel Plus Placebo in Advanced/​Metastatic Non-Squamous NSCLC After PD-1/​PD-L1 Therapy and Platinum Chemotherapy (DUBLIN-4). ClinicalTrials.gov. Updated September 29, 2026. Accessed September 30, 2026. https://clinicaltrials.gov/study/NCT07361484

3. Han B, Feinstein T, Shi Y, et al. Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med. 2024;12(10):775-786. doi:10.1016/S2213-2600(24)00178-4