BeyondSpring Presents Efficacy/Safety Data from a Phase 2 Study of Pembrolizumab plus Plinabulin/Docetaxel in Metastatic NSCLC after Progressing on First-Line Immune Checkpoint Inhibitors at 2025 ASCO Annual Meeting

Rhea-AI Summary

BeyondSpring (NASDAQ: BYSI) presented promising Phase 2 data for their 303 Study at the 2025 ASCO Annual Meeting, evaluating the combination of Plinabulin, pembrolizumab, and docetaxel in metastatic NSCLC patients who progressed on first-line PD-1/L1 inhibitors. The study of 47 patients showed impressive results with median PFS of 6.8 months (nearly double the standard of care), Disease Control Rate of 77.3%, and 15-month OS rate of 78%. The treatment demonstrated an 18.2% Objective Response Rate and was well-tolerated, with 51.1% of patients experiencing grade 3 or higher treatment-related adverse effects. Plinabulin, as a first-in-class tubulin binder, shows potential to address acquired resistance to checkpoint inhibitors through its dual innate and adaptive immune mechanism.

Positive

• Median PFS of 6.8 months is nearly double the 3.7 months seen with current standard of care docetaxel
• High Disease Control Rate of 77.3% indicating clinical benefit in majority of patients
• Strong 15-month Overall Survival rate of 78%, surpassing standard of care
• Higher Objective Response Rate (18.2%) compared to standard of care docetaxel (12.8%)
• Well-tolerated safety profile with no treatment-related deaths

Negative

• 51.1% of patients experienced grade 3 or higher treatment-related adverse effects
• 14.9% of patients experienced GI side effects
• 14.9% of patients experienced transient hypertension

Insights

Oncology Clinical Trials Expert

BeyondSpring's triple therapy shows promising Phase 2 results for NSCLC patients who failed immunotherapy, significantly outperforming standard care.

BeyondSpring's Phase 2 trial results for their triple combination therapy (Plinabulin + pembrolizumab + docetaxel) represent a potentially significant advancement for non-small cell lung cancer patients who've developed resistance to first-line immunotherapy. The data demonstrates meaningful clinical improvements over the current standard of care.

The most compelling efficacy signals include a median progression-free survival of 6.8 months - nearly double the 3.7 months observed with docetaxel alone. The disease control rate of 77.3% is particularly noteworthy, suggesting most patients derived clinical benefit despite previously progressing on PD-1/L1 inhibitors. The 15-month overall survival rate of 78% (with median OS not yet reached) also appears promising compared to historical docetaxel outcomes.

The safety profile appears manageable with 51.1% of patients experiencing grade 3+ treatment-related adverse effects, primarily GI side effects and transient hypertension (both 14.9%), with no treatment-related deaths reported.

This addresses a critical unmet need in the approximately 60% of NSCLC patients who develop resistance to checkpoint inhibitors. The current standard treatment for these patients - docetaxel - was approved 25 years ago and has limited efficacy with significant toxicity concerns.

Plinabulin's novel mechanism as a tubulin binder that activates GEF-H1, triggering dendritic cell maturation and T-cell activation, potentially explains its ability to help re-sensitize tumors to immunotherapy. This "immune re-sensitization" approach could represent an important new treatment paradigm if confirmed in larger studies.

While promising, these remain interim Phase 2 results with limitations including the single-arm study design, relatively small sample size (47 patients), and still-maturing data. A randomized Phase 3 trial would be needed to definitively establish superiority over current standards.

• Median PFS at 6.8 months, Disease Control Rate of 77.3%, 15 months OS% at 78% in Metastatic NSCLC Patients after Progression on PD-1/L1 Therapies
  

FLORHAM PARK, N.J., June 03, 2025 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a clinical-stage global biopharmaceutical company focused on developing cancer therapies, today announces that it presented interim phase 2 data on the 303 Study, a study in 2L/3L non-small cell lung cancer (NSCLC) after disease progression on 1L PD-1/L1 inhibitors with and without chemotherapy (NCT05599789), with financial support from Merck’s (Rahway, NJ USA) Investigator Studies Program and provision of study drug, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, on May 31^st, 2025 in Chicago, IL.

The single study finished enrollment of 47 patients with patients treated with Plinabulin, pembrolizumab and docetaxel on day 1 of each cycle until disease progression or intolerable severe adverse events. All patients progressed on PD-1/L1 inhibitors, including 78% who received pembrolizumab. Of the 47 patients, the median age was at 67 ranging from 44 to 83; 80.9% were male and 19.1% were female; 72.3% were current or former smokers. Histology included 63.8% patients with non-squamous cell carcinoma and 36.2% with squamous cell carcinoma. The median follow-up was 12.7 months. As of the data cut-off date of May 16, 2025, there are patients still responding to the therapy; therefore, the final data will be updated. The key results at the database lock are summarized below.

• Median Progression-Free Survival (PFS): 6.8 months — nearly double the 3.7 months seen with current standard of care (SOC) docetaxel¹
• Confirmed Objective Response Rate (ORR): 18.2% — higher than the 12.8% seen with SOC docetaxel¹
• Disease Control Rate (DCR: PR + SD > 4 months): 77.3% — indicating clinical benefit majority of patients who progressed on prior PD-1/L1 inhibitors
• Median Duration of Response (DoR): 7.2 months
• 6-Month PFS Rate: 56%
• 15-Month Overall Survival (OS) Rate: 78% (median OS not yet reached) – longer than median OS of 11.8 months for SOC docetaxel¹  
• The combination was well tolerated. 51.1% of patients experienced grade 3 or higher treatment-related adverse effects, including GI side effects of 14.9% and transient hypertension of 14.9%. There were no treatment-related deaths.
  

“These promising Phase 2 results reinforce Plinabulin’s potential as a first-in-class therapy that addresses one of the most urgent challenges in oncology—acquired resistance to checkpoint inhibitors,” said Dr. Lan Huang, PhD, Co-Founder, Chairman and CEO of BeyondSpring.

“By restoring immune sensitivity and improving progression-free survival, disease control rate and overall survival, Plinabulin opens a new therapeutic path for the more than 60% of patients who stop responding to PD-1/L1 therapies. We are encouraged by these data and committed to advancing Plinabulin in combination strategies to meet critical unmet needs in lung cancer and beyond.”

A New Potential Pathway to Re-Sensitize Tumors to Immunotherapy

Immune checkpoint inhibitor (ICI)-based regimens have remained as the standard of care for first-line treatment of NSCLC, but over 60% patients could progress from ICI². “Acquired resistance” to ICI could be caused by “T cell exhaustion” or “antigen presenting cell pathway mutation”². Once progressed, it is not recommended to continue using ICI monotherapy. This underscores a substantial unmet need for more effective treatment options.

With over 700 cancer patients treated with good tolerability, Plinabulin is a first-in-class, late-stage, differentiated tubulin binder that activates GEF-H1, triggering dendritic cell (DC) maturation and T cell activation, and reduce chemotherapy induced neutropenia^3,4,5. This dual innate and adaptive immune mechanism has demonstrated Plinabulin’s strong potential to reverse “acquired resistance to ICI” and to enhance the efficacy and tolerability of both PD-1/L1 inhibitors and chemotherapy-based regimens.

“This patient population—those who relapse after checkpoint inhibitors—faces a grim outlook with limited options,” said Dr. Mengzhao Wang, Principal Investigator and Chief of Respiratory and Critical Care Medicine at Peking Union Medical College Hospital. “Second- and third-line NSCLC with no actionable driver mutation after progression of ICIs is a critical unmet medical need, with no new agent approval in the last decade. The current SOC docetaxel, approved 25 years ago, has limited efficacy and over 40% severe neutropenia. With Plinabulin’s benefit in significantly reducing severe neutropenia of docetaxel in a number of studies, this promising Phase 2 efficacy data suggests the triple combination may provide both efficacy and safety benefit in a meaningful way. We are encouraged and look forward to further study.”

2025 ASCO Poster Presentation: Phase 2 Study of Pembrolizumab (Pembro) plus Plinabulin (Plin) and Docetaxel (Doc) for Patients (Pts) with Metastatic NSCLC after Progression on First-line Immune Checkpoint Inhibitor Alone or Combination Therapy: Initial Efficacy and Safety Results on Immune Re-sensitization

• Presenter / Author: Yan Xu, Minjiang Chen, Xiaoxing Gao, Xiaoyan Liu, Jing Zhao, Wei Zhong, Ruili Pan, Mengzhao Wang
• Poster Session: Lung Cancer – Non-Small Cell Metastatic
• Abstract Number: 8560
  

References

1. Ahn M-J, et al., Datopotamab Deruxtecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III TROPION-Lung01 Study. Journal of Clinical Oncology 2024; 43 (3): 260-272.
2. Memon D et al. Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer. Cancer Cell 2024; 42, 209–224.
3. La Sala G. et al. Structure, Thermodynamics, and Kinetics of Plinabulin Binding to Two Tubulin Isotypes. Chem 2019; 5(11): 2969-2986.
4. Kashyap AS et al. GEF-H1 signaling upon microtubule destabilization is required for dendritic cell activation and specific anti-tumor responses. Cell Reports 2019; 28(13):3367–3380.
5. Han 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 Respiratory Medicine 2024; 12(10):775-786.
   

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 checkpoint inhibitors. Learn more at beyondspringpharma.com.

About 303 Study
303 Study is an open-label, single-arm Phase 2 Study of Plinabulin plus docetaxel and pembrolizumab for previously treated patients with metastatic NSCLC and progressive disease after anti-PD-(L)1 inhibitor alone or in combination with platinum-doublet chemotherapy. This study evaluates the efficacy and safety of this triple combination and is being conducted at Peking Union Medical College Hospital, Beijing, China with Dr. Mengzhao Wang, Chief of the Department of Respiratory and Critical Care Medicine, as the principal investigator and with Merck. The sample size of the study is 47 patients and all have been enrolled. The primary endpoint is investigator-based ORR (RECIST 1.1). The secondary endpoints include PFS, OS, DoR, and safety.

The regimen includes three agents given on day 1 of each 21-day cycle:

• Pembrolizumab 200 mg IV Q3W;
• Docetaxel 75 mg/m2 IV Q3W;
• Plinabulin 30mg/m2 IV Q3W.
  

The study is funded by Merck’s Investigator Studies Program with provision of study drug and financial support. The registration number is NCT05599789 on clinicaltrials.gov.

Investor Contact:
IR@beyondspringpharma.com

Media Contact:
PR@beyondspringpharma.com

FAQ

What are the key efficacy results from BeyondSpring's Phase 2 NSCLC trial for BYSI stock?

The trial showed median PFS of 6.8 months, Disease Control Rate of 77.3%, Objective Response Rate of 18.2%, and 15-month OS rate of 78%, significantly outperforming standard of care docetaxel.

How does Plinabulin work in treating NSCLC patients who progressed on immunotherapy?

Plinabulin is a first-in-class tubulin binder that activates GEF-H1, triggering dendritic cell maturation and T cell activation, potentially reversing acquired resistance to immune checkpoint inhibitors.

What are the main side effects reported in BeyondSpring's Phase 2 NSCLC trial?

51.1% of patients experienced grade 3 or higher treatment-related adverse effects, including 14.9% GI side effects and 14.9% transient hypertension, with no treatment-related deaths.

How many patients were enrolled in BeyondSpring's Phase 2 NSCLC trial?

The trial enrolled 47 patients with a median age of 67, including 80.9% male and 19.1% female patients, with 72.3% being current or former smokers.

What is the significance of BeyondSpring's trial results for NSCLC treatment?

The results suggest a potential new treatment option for the over 60% of NSCLC patients who develop resistance to first-line checkpoint inhibitors, addressing a significant unmet medical need.