BeyondSpring Drug Triggers Immune Response in Patients Who Failed Prior Cancer Immunotherapy

Author: Benzinga Newsdesk | July 07, 2025 06:04am

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.
   

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