BeyondSpring Publishes Human Clinical Study in Med (Cell Press) Showing Plinabulin-Driven Dendritic Cell Maturation and Tumor Response After Prior Checkpoint Inhibitor Failure

• In eight tumors where patients failed immune checkpoint inhibitor (ICI) treatment, Plinabulin + radiation + PD-1 inhibitors demonstrated an overall response rate (ORR) of 23% and a disease control rate (DCR) of 54% in non-irradiated lesions.
• Biomarker analysis linked Plinabulin’s mechanism to GEF-H1–dependent dendritic cell maturation, offering the potential to pre-select patients at baseline and predict clinical response.
  
  

FLORHAM PARK, N.J., July 07, 2025 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) today announced publication of a human clinical study in Med (Cell Press) demonstrating that Plinabulin, when combined with radiation and a checkpoint inhibitor, induces dendritic cell (DC) maturation and elicits tumor responses in patients across multiple cancer types who had failed prior ICI therapy. The study also identified a potential biomarker—baseline GEF-H1 immune signature—that may enable patient pre-selection and clinical response prediction.

“These results offer early but important signals that Plinabulin’s dendritic cell maturation mechanism could play a pivotal role in reversing ICI-acquired resistance,” said Dr. Steven Lin, M.D., Ph.D., corresponding author and Professor of Radiation Oncology at The University of Texas MD Anderson Cancer Center. “The ability of Plinabulin to activate the immune system in this setting is both scientifically intriguing and clinically promising—particularly given the durability of responses in some heavily pretreated patients.”

Dr. Lin added, “It is especially noteworthy that Plinabulin combination demonstrated the best responses in non-small cell lung cancer, head and neck squamous cell carcinoma, and Hodgkin lymphoma.”

“This study builds upon the seminal work of Nobel Laureate Dr. Ralph Steinman and Dr. Ira Mellman, who helped define the essential role of dendritic cells in immune activation,” said Lan Huang, Ph.D., Co-Founder, Chairman, and CEO of BeyondSpring. “Plinabulin’s ability to drive dendritic cell maturation and induce immune responsiveness offers a potential breakthrough strategy for patients who are refractory or relapsed on checkpoint inhibitors. We are committed to advancing Plinabulin’s development in partnership with pioneering cancer research institutions like MD Anderson.”

Triple I/O Combination Study Highlights

This investigator-initiated, Phase 1 translational trial (NCT04902040) evaluated a triple immunotherapy approach combining Plinabulin, radiation (RT), and anti-PD-1 checkpoint inhibitors in patients with eight cancer types who are refractory or relapsed on prior ICI therapy. RT was administered only during the first cycle. The primary endpoint was tumor response in non-irradiated lesions.

• Clinical Results
  Nineteen patients received the combination regimen—14 on pembrolizumab and 5 on nivolumab. Tumor responses were evaluable in 13 ICI-relapsed patients across eight tumor types. Objective response rate (ORR) was 23%, and disease control rate (DCR) was 54%. Clinically meaningful benefits (PR, partial response; SD, stable disease) were observed in NSCLC (2/2), HNSCC (2/3), and Hodgkin lymphoma (2/2). Both Hodgkin lymphoma patients had durable responses exceeding 19 months despite 12–16 prior lines of therapy.
• Mechanism Confirmation
  Plinabulin triggered DC maturation post-RT via GEF-H1 signaling. Flow cytometry of whole blood revealed increased expression of DC maturation markers (CCR7, CD80, CD83) and a shift in monocyte subpopulations from classical to proinflammatory phenotype in responders.
• Biomarker Insight
  Single-cell RNA sequencing differentiated responders from non-responders and identified baseline GEF-H1 immune gene expression as a potential predictive biomarker for Plinabulin response.
  
  

About the Med Publication

Lin S.H., Subbiah V., Cohen E.N. et al. “Plinabulin following radiation enhances dendritic cell maturation and checkpoint inhibitor retreatment of relapsed/refractory cancers.” Med. Published June 27, 2025. (https://www.cell.com/med/abstract/S2666-6340(25)00179-5)

About the Plinabulin Basket Study

This open-label, single-arm Phase 1 basket study (NCT04902040) at MD Anderson Cancer Center investigates safety and efficacy of Plinabulin plus radiation and PD-1 inhibitor in patients refractory or relapsed after prior immunotherapy. The primary endpoint is investigator-assessed ORR (RECIST 1.1) in non-irradiated lesions; secondary endpoints include DCR.

• Regimen
  – Radiation (Cycle 1 and optional Cycle 2): Local consolidative RT (8 Gy × 3; 12.5 Gy × 4; or 4 Gy × 5) on Day 1. Optional sequential RT in Cycle 2 at investigator discretion.
  – Plinabulin: 30 mg/m² on Days 1 and 4 of Cycle 1 (3–6 hours post-RT); Day 1 of Cycle 2 onward; Additional Day 4 in Cycle 2 if RT is given in Cycle 2.
  – PD-1 inhibitor: Pembrolizumab 200 mg on Day 1 every 21 days or nivolumab 240 mg on Day 1 every 14 days × 2 doses per cycle.
  
  

About Plinabulin

Plinabulin is a first-in-class dendritic cell maturation agent that binds reversibly to a unique site on tubulin, destabilizing microtubules in a controlled manner to release GEF-H1 (Chem 2019; Cell Reports 2019). Immune protein GEF-H1 activates the RhoA/ROCK signaling pathway, promoting dendritic cell maturation and anti-tumor T-cell immunity. This mechanism is distinct from traditional tubulin agents and does not interfere with tubulin stabilizers like docetaxel.

Across multiple clinical studies and approximately 800 patients, Plinabulin has shown durable anti-cancer activity and a favorable safety profile, and has significantly reduced chemotherapy-induced neutropenia, potentially enhancing docetaxel tolerability.

• Prior Findings:
  – In the Dublin-3 Phase 3 second and third line (2/3L) NSCLC, EGFR wild-type trial (n=559), Plinabulin + docetaxel demonstrated a significant overall survival benefit over standard-of-care docetaxel (Lancet Respiratory Medicine 2024 - Press Release Link).
  – In a Phase 2 study of Plinabulin + pembrolizumab + docetaxel in 2/3L NSCLC who progressed on PD-1/L1 inhibitors (n=47), median PFS was 6.8 months, and 15-month OS rate was 78% (ASCO 2025 - Press Release Link).
  
  

About BeyondSpring

BeyondSpring (NASDAQ: BYSI) is a clinical-stage biopharmaceutical company developing first-in-class therapies for high unmet medical needs. Its lead asset, Plinabulin, is in late-stage clinical development as an anti-cancer agent in NSCLC and a range of cancer indications. Plinabulin’s novel mechanism of action as a dendritic cell maturation agent supports both anti-cancer activity and immune modulation, offering a unique approach to resensitizing tumors to prior failure or progression to checkpoint inhibitors.

In addition, BeyondSpring is the founding equity holder of SEED Therapeutics, a biotechnology company pioneering targeted protein degradation (TPD) through the discovery of novel molecular glues and bifunctional degraders. Powered by its proprietary RITE3™ platform, SEED is advancing a pipeline of first-in-class degraders to address traditionally undruggable targets across oncology, neurodegeneration, immunology, and virology. SEED’s strategic collaborations with Eli Lilly and Company and Eisai Co., Ltd. support its mission to develop transformational therapies. Learn more at beyondspringpharma.com.

Investor Contact:
IR@beyondspringpharma.com

Media Contact:
PR@beyondspringpharma.com

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