On June 3, 2025 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a clinical-stage global biopharmaceutical company focused on developing cancer therapies, reported 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) (Free ASCO Whitepaper) Annual Meeting, on May 31st, 2025 in Chicago, IL (Press release, BeyondSpring Pharmaceuticals, JUN 3, 2025, View Source;utm_medium=rss&utm_campaign=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 [SID1234653667]).
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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):8 months — nearly double the 3.7 months seen with current standard of care (SOC) docetaxel1
Confirmed Objective Response Rate (ORR):2% — higher than the 12.8% seen with SOC docetaxel1
Disease Control Rate (DCR: PR + SD > 4 months):3% — indicating clinical benefit majority of patients who progressed on prior PD-1/L1 inhibitors
Median Duration of Response (DoR):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. 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 neutropenia3,4,5. 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 (Free ASCO Whitepaper) 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