BeyondSpring Publishes Human Clinical Study in Med (Cell Press) Showing Plinabulin-Driven Dendritic Cell Maturation and Tumor Response After Prior Checkpoint Inhibitor Failure
BeyondSpring (NASDAQ: BYSI) has published significant clinical results in Med (Cell Press) demonstrating the effectiveness of Plinabulin in combination with radiation and checkpoint inhibitors for cancer treatment. The study showed an overall response rate (ORR) of 23% and a disease control rate (DCR) of 54% in patients who previously failed immune checkpoint inhibitor (ICI) therapy.
The research revealed that Plinabulin works through GEF-H1-dependent dendritic cell maturation, with particularly strong responses in non-small cell lung cancer, head and neck squamous cell carcinoma, and Hodgkin lymphoma. Notably, Hodgkin lymphoma patients demonstrated durable responses exceeding 19 months despite having undergone 12-16 prior lines of therapy.
BeyondSpring (NASDAQ: BYSI) ha pubblicato risultati clinici significativi su Med (Cell Press) che dimostrano l'efficacia di Plinabulin in combinazione con radiazioni e inibitori del checkpoint immunitario per il trattamento del cancro. Lo studio ha evidenziato un tasso di risposta globale (ORR) del 23% e un tasso di controllo della malattia (DCR) del 54% nei pazienti che avevano precedentemente fallito la terapia con inibitori del checkpoint immunitario (ICI).
La ricerca ha mostrato che Plinabulin agisce tramite la maturazione delle cellule dendritiche dipendente da GEF-H1, con risposte particolarmente forti nel carcinoma polmonare non a piccole cellule, nel carcinoma squamoso della testa e del collo e nel linfoma di Hodgkin. Da notare che i pazienti con linfoma di Hodgkin hanno mostrato risposte durature superiori a 19 mesi nonostante avessero già seguito 12-16 linee di terapia precedenti.
BeyondSpring (NASDAQ: BYSI) ha publicado resultados clínicos significativos en Med (Cell Press) que demuestran la eficacia de Plinabulin en combinación con radiación e inhibidores de puntos de control para el tratamiento del cáncer. El estudio mostró una tasa de respuesta global (ORR) del 23% y una tasa de control de la enfermedad (DCR) del 54% en pacientes que previamente no respondieron a la terapia con inhibidores de puntos de control inmunitarios (ICI).
La investigación reveló que Plinabulin actúa a través de la maduración de células dendríticas dependiente de GEF-H1, con respuestas especialmente fuertes en cáncer de pulmón de células no pequeñas, carcinoma de células escamosas de cabeza y cuello, y linfoma de Hodgkin. Cabe destacar que los pacientes con linfoma de Hodgkin demostraron respuestas duraderas superiores a 19 meses a pesar de haber recibido entre 12 y 16 líneas previas de tratamiento.
BeyondSpring (NASDAQ: BYSI)은 Med (Cell Press)에 암 치료를 위한 방사선 및 체크포인트 억제제와 병용한 Plinabulin의 효과를 입증하는 중요한 임상 결과를 발표했습니다. 연구에서는 이전에 면역 체크포인트 억제제(ICI) 치료에 실패한 환자들에서 전체 반응률(ORR) 23%과 질병 조절률(DCR) 54%를 보였습니다.
연구 결과 Plinabulin은 GEF-H1 의존성 수지상 세포 성숙을 통해 작용하며, 비소세포폐암, 두경부 편평세포암, 그리고 호지킨 림프종에서 특히 강한 반응을 나타냈습니다. 특히, 호지킨 림프종 환자들은 12~16회의 이전 치료에도 불구하고 19개월 이상의 지속적인 반응을 보였습니다.
BeyondSpring (NASDAQ : BYSI) a publié des résultats cliniques importants dans Med (Cell Press) démontrant l'efficacité de Plinabulin en combinaison avec la radiothérapie et les inhibiteurs de points de contrôle pour le traitement du cancer. L'étude a montré un taux de réponse globale (ORR) de 23% et un taux de contrôle de la maladie (DCR) de 54% chez des patients ayant précédemment échoué à une thérapie par inhibiteurs de points de contrôle immunitaire (ICI).
La recherche a révélé que Plinabulin agit via une maturation des cellules dendritiques dépendante de GEF-H1, avec des réponses particulièrement marquées dans le cancer du poumon non à petites cellules, le carcinome épidermoïde de la tête et du cou, ainsi que le lymphome de Hodgkin. Notamment, les patients atteints de lymphome de Hodgkin ont présenté des réponses durables dépassant 19 mois malgré 12 à 16 lignes de traitement antérieures.
BeyondSpring (NASDAQ: BYSI) hat bedeutende klinische Ergebnisse in Med (Cell Press) veröffentlicht, die die Wirksamkeit von Plinabulin in Kombination mit Strahlentherapie und Checkpoint-Inhibitoren zur Krebsbehandlung belegen. Die Studie zeigte eine Gesamtansprechrate (ORR) von 23% und eine Krankheitskontrollrate (DCR) von 54% bei Patienten, bei denen die Immun-Checkpoint-Inhibitor-Therapie (ICI) zuvor versagt hatte.
Die Forschung ergab, dass Plinabulin durch GEF-H1-abhängige Reifung dendritischer Zellen wirkt, mit besonders starken Reaktionen bei nicht-kleinzelligem Lungenkrebs, Plattenepithelkarzinom des Kopf- und Halsbereichs sowie Hodgkin-Lymphom. Bemerkenswert ist, dass Hodgkin-Lymphom-Patienten dauerhafte Reaktionen von über 19 Monaten zeigten, obwohl sie bereits 12–16 vorherige Therapielinien durchlaufen hatten.
- None.
- Limited sample size with only 13 evaluable patients
- Study is still in early Phase 1 stage
Insights
BeyondSpring's Plinabulin shows promise in reversing checkpoint inhibitor resistance with 23% response rate and identified predictive biomarker.
BeyondSpring's publication in Med (Cell Press) represents a scientifically significant development in immuno-oncology. The study evaluated Plinabulin combined with radiation and PD-1 inhibitors in patients who failed prior checkpoint inhibitor therapy—a challenging patient population with limited treatment options.
The clinical results are noteworthy: an
The mechanistic findings are equally important. The study confirms Plinabulin's novel mechanism of action through GEF-H1-dependent dendritic cell maturation. Dendritic cells are critical antigen-presenting cells that bridge innate and adaptive immunity—their proper activation is essential for effective anti-tumor immune responses. The identification of flow cytometry markers (CCR7, CD80, CD83) and monocyte phenotype shifts provides clear pharmacodynamic evidence of Plinabulin's immunomodulatory activity.
Perhaps most valuable is the identification of a baseline GEF-H1 immune signature as a potential predictive biomarker. This could enable precision medicine approaches by pre-selecting patients likely to respond to Plinabulin combinations, addressing a key challenge in immuno-oncology: identifying the right therapy for the right patient.
While promising, this is a Phase 1 study with a modest sample size (13 evaluable patients), so larger trials will be needed to confirm these findings. Nevertheless, the biological rationale, preliminary efficacy signals, and biomarker development represent a meaningful advancement in addressing immune checkpoint inhibitor resistance.
- 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) of54% 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) was23% , and disease control rate (DCR) was54% . 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 was78% (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
FAQ
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