BYSI BeyondSpring Inc

BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, today 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, with financial support from Merck & Co., Inc’s (NYSE: MRK, known as MSD outside of the United States and Canada) Investigator Studies Program and provision of study drug, at the European Society for Medical Oncology (ESMO) Congress 2024, on September 14, 2024 in Barcelona, Spain.

Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations who progress on 1L immune checkpoint inhibitors (ICI) with and without standard chemotherapy, with an overall response rate (ORR) of 12.8% and median PFS (mPFS) of 3.7 months in TROPION Lung-01 phase 3 studies. In metastatic NSCLC resistant to previous PD-1/L1 therapy1, PD-L1 and CTLA-4 inhibition alone or in combination with hypofractionated radiotherapy produced limited clinical benefits with ~11.5% ORR.

This investigator-initiated, single-arm, open-label, phase 2 study (KeyPelms-004 or 303 Study) evaluates the efficacy and safety of a triple combination regimen of pembrolizumab plus plinabulin/docetaxel (NCT05599789). The study intends to enroll a total of 47 patients and is ongoing at Peking Union Medical College Hospital, Beijing, China with the principal investigator Dr. Mengzhao Wang, Chief of the Department of Respiratory and Critical Care Medicine. Here, we report on a planned formal interim analysis of 19 patients.

At the database lock on 29 April 2024, 29 patients were enrolled and 19 were evaluable for stage 1 data analysis. All patients experienced disease progression after initial clinical benefit with ICI. Of the 19 evaluable patients (median age at 66.4 years; ranged 50-76 years), 68.4% were male and 31.6% were female; 57.9% were current or former smokers. Histology included 57.9% patients with non-squamous cell carcinoma and 42.1% with squamous cell carcinoma. The median follow-up was 8.67 months. Below is an efficacy summary table.

Primary Endpoint	Plinabulin + Pembrolizumab + Docetaxel (n=19)
Confirmed ORR (RECIST 1.1)	21.1%
Secondary Endpoints
Median PFS (RECIST 1.1)	8.63 M(6 M PFS rate: 67.1%;12 M PFS rate: 49.2%)
Median OS (Overall Survival)	Not reached
Median DoR (Duration of Response)	11.40 M
Disease Control Rate(PR + SD > 4 months)	89.5%

• The combination was well tolerated. 52.6% of patients experienced grade 3 or higher treatment-related adverse effects. There were no treatment-related deaths.

“Plinabulin is a potent inducer of dendritic cell or DC maturation that leads to T cell activation. DC is the most potent antigen presenting cell (APC). This unique mechanism of action reinforces anti-tumor immune response with the potential to overcome acquired ICI resistance, which may derive from APC pathway mutation or T cell exhaustion. Compared to historical controls of 3-4 months of median PFS2, this study’s early efficacy data doubled median PFS to 8.6 months, with an impressive disease control rate of almost 90%, which is encouraging and clinically meaningful for this severe unmet need,” said Dr. Mengzhao Wang, principal investigator at Peking Union Medical College Hospital.

ESMO Congress 2024 (1330P): Phase 2 Study of Pembrolizumab plus Plinabulin and Docetaxel for Patients (pts) with Metastatic NSCLC after Failure on First-line Immune Checkpoint Inhibitor Alone or Combination Therapy: Initial Efficacy and Safety Results on Immune Re-sensitization

• Presenter: Dr. Yan Xu, Peking Union Medical College Hospital, Beijing, China
• Poster Session: NSCLC, metastatic

References:

1. Schoenfeld et al. 2022, Lancet Oncology 23:279-291
2. TROPION Lung-01: https://doi.org/10.1200/JCO-24-01544

About PlinabulinPlinabulin is a novel first-in-class dendritic cell maturation therapeutic with durable anti-cancer benefit observed across multiple clinical studies. As a reversible binder at a distinct tubulin pocket, plinabulin does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel, which contributes to its differentiated activity and tolerability compared to other tubulin binders. In addition, plinabulin significantly reduces chemotherapy induced neutropenia and could thereby increase docetaxel tolerability. Over 700 patients have been treated with plinabulin with good tolerability.

About KeyPelms-004 or 303 Study303 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. The regimen includes Pembrolizumab 200 mg IV every 3 weeks (Q3W) on Day 1, Docetaxel 75 mg/m2 IV Q3W on Day 1 and Plinabulin 30mg/m2 IV Q3W on Day 1 in a 21-day cycle. The primary endpoint is investigator-based ORR (RECIST 1.1). The secondary endpoints include PFS, OS, DoR, and safety. The study intends to enroll 47 patients with a formal interim analysis of 19 patients enrolled. The study is funded by Merck’s Investigator Studies Program with provision of study drug and financial support.​​About BeyondSpringBeyondSpring is a global clinical-stage biopharmaceutical company developing innovative therapies to improve clinical outcomes for patients with high unmet medical needs. The Company is advancing its first-in-class lead asset, Plinabulin, a potent inducer of dendritic cell maturation, in late-stage clinical development as a direct anti-cancer agent in NSCLC and a variety of cancer indications. BeyondSpring’s pipeline also includes three preclinical immuno-oncology assets. Additionally, BeyondSpring is an equity owner of SEED Therapeutics, Inc which is a pioneer in Target Protein Degradation technology and its application in innovative drug development. Learn more by visiting https://beyondspringpharma.com.

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