An Open-Label, Single-Arm, Phase II Study of Pembrolizumab, Plinabulin Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer

Monoclonal antibodies against programmed death 1 (PD-1) and its ligand PD-L1 have shown efficacy in patients with ES-SCLC in the monotherapy and combination therapy settings. Up to now, Atezolizumab and Durvalumab has been approved for first line treatment for ES-SCLC in China combined with EP or EC. Besides, KEYNOTE-604 study revealed that adding pembrolizumab to standard first-line EP significantly improves PFS in patients with ES-SCLC and is associated with durable responses in a subset of patients. 12-m PFS rate were 13.6% with pembrolizumab plus EP and 3.1% with placebo plus EP. The statistical threshold for declaring significant prolongation of OS was narrowly missed. Considering sicker pts was enrolled and the interim analysis was quite often, even though the investigators narrowly missed the OS endpoint, longer numerical OS data was observed. The latest version of NCCN SCLC guidelines still recommended pembrolizumab as an option for ES-SCLC patients.
Plinabulin received breakthrough designation from both US and China FDA for CIN (Chemotherapy Induced Neutropenia) prevention indication. As a "pipeline in a drug," plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody resistant patients. In a poster released at 2021 ASCO conference, a phase I trial of Plinabulin in combination with nivolumab and ipilimumab in patients with relapsed small cell lung cancer: Big Ten Center Research Consortium (BTCRC-LUN17-127) study. Plinabulin in combination with nivolumab and ipilimumab was safe and well tolerated with promising efficacy signal of 46% ORR.
From above, Pembrolizumab, Plinabulin plus Etoposide and Platinum as First-Line Therapy for ES-SCLC should be a promising combination therapy, as the investigators expect increased efficacy and reduced toxicity with the addition of Plinabulin. In this proof of concept phase II study, the investigators will investigate that the efficacy and safety of Pembrolizumab, Plinabulin plus Etoposide and Platinum as First-Line Therapy for ES-SCLC.

Start Date07 Mar 2024

Sponsor / Collaborator

Wuhan Xiehe Hospital Tower

NCT05130827

/ Active, not recruitingPhase 2IIT

Pilot Trial of Plinabulin and Pegfilgrastim to Reduce the Duration of Absolute Neutropenia After Autologous Hematopoietic Cell Transplantation for Patients With Multiple Myeloma

This study will see how long it takes for white blood cell counts to return to normal in people with multiple myeloma (MM) who receive plinabulin and pegfilgrastim after undergoing an autologous hematopoietic stem cell transplant (AHCT).

Start Date21 Dec 2021

Sponsor / Collaborator

Memorial Sloan Kettering Cancer Center

[+1]

NCT04902040

/ TerminatedPhase 1/2IIT

An Open-label, Single-Center, Phase 1b/2 Study to Evaluate the Safety of Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Malignancies After Progression on PD-1 or PD-L1 Targeted Antibodies

This phase Ib/II trial studies the side effects and best dose of plinabulin in combination with radiation therapy and immunotherapy in patients with select cancers that have spread to other places in the body (advanced) after progression on PD-1 or PD-L1 targeted antibodies. Plinabulin blocks tumor growth by targeting both new and existing blood vessels going to the tumor as well as killing tumor cells. Immunotherapy may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving plinabulin in combination with radiation therapy and immunotherapy may work better in treating advanced cancers.

Start Date14 Apr 2021

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with Plinabulin

100 Translational Medicine associated with Plinabulin

100 Patents (Medical) associated with Plinabulin

114

Literatures (Medical) associated with Plinabulin

17 Jan 2025·Medicine

Osteosarcoma biomarker analysis and drug targeting prediction based on pyroptosis-related genes

Article

Author: Li, Xiaofeng ; Zhuang, Yuxiang

Osteosarcoma is a malignant bone tumor originating from mesenchymal tissue. Recent studies have found that the tumor inflammatory microenvironment plays an important role in promoting the malignant characteristics and metastatic potential of malignant tumors. Pyroptosis, an inflammatory programmed cell death, elicits immune responses that exhibit anti-tumor effects through released factors and contents. Therefore, improving anti-tumor immunity by targeting osteosarcoma-related pyroptosis genes and pathways may be of great significance in delaying early metastasis of osteosarcoma and improving patient survival rate. The study aimed to identify pyroptosis-related genes and biomarkers in osteosarcoma, predicting therapeutic drugs targeting these genes. Gene expression profiles of osteosarcoma were retrieved from Gene Expression Omnibus and cross-referenced with GeneCards and Comparative Toxicogenomics Database to identify differentially expressed pyroptosis-related genes. We conducted enrichment analysis on intersecting genes to identify their biological processes and signaling pathways and assessed immune cell composition in the tumor microenvironment through immune infiltration analysis. In addition, we further utilized Cytoscape software to screen out the top 10 genes with Degree values among the intersected genes as hub genes and performed GSEA analysis and drug prediction based on the hub genes. A total of 22 differentially expressed pyroptosis-related genes were identified in osteosarcoma, with 10 of them (TP53, CYCS, IL-1A, IL-1B, IL-18, CASP-3, CASP-8, IL-6, TNF, CASP-1) pinpointed as hub genes. Enrichment analysis found that the 22 intersection genes are mainly associated with pyroptosis, apoptosis, immune regulation, and related biological processes. The results of data validation targeting hub genes suggest that IL-18, CASP-1, and CASP-8 may be key genes involved in the regulation of pyroptosis in osteosarcoma. Immune infiltration analysis shows statistical differences in the distribution of immune cells like naive B cells, monocytes, M2 macrophages, and dendritic/mast cells, suggesting they play a role in the osteosarcoma tumor microenvironment. Hub gene drug targets suggest Triethyl phosphate, Plinabulin, and Siltuximab as potential osteosarcoma treatments. Our findings suggest potential mechanisms of action for 22 pyroptosis-related genes in osteosarcoma and preliminarily predicted that the occurrence of osteosarcoma is closely related to pyroptosis, apoptosis, and immune regulation. Predicted Triethyl phosphate, Plinabulin, Siltuximab as potential osteosarcoma treatments.

01 Jan 2025·Iranian journal of basic medical sciences

Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma.

Article

Author: Li, Yangling ; Wu, Rui ; Zhang, Chong ; Zhang, Huanqi ; Luo, Kaizhi ; Wang, Rouxin ; Zhu, Yuanheng ; Cheng, Jing

ObjectivesPlinabulin, a marine-derived anticancer drug targeting microtubules, exhibits anti-cancer effects on glioblastoma cells. However, its therapeutic potential, specifically for glioblastoma treatment, remains underexplored. This study aims to elucidate the mechanisms by which plinabulin exerts its effects on glioblastoma cells.Materials and MethodsUsing the SRB and colony formation assay to observe the effect of plinabulin on glioblastoma cell viability. Wound healing and transwell migration assay were used to test the effect of plinabulin on glioblastoma cell metastatic potential. Crucial target genes were identified through RNA sequencing and bioinformatics analysis. Protein levels were evaluated in a concentration-dependent manner using western blot analysis.ResultsPlinabulin suppressed glioblastoma cell proliferation by causing cell cycle G2/M phase arrest and inhibited migration. The IC50 values were 22.20 nM in A172 cells and 20.55 nM in T98G cells. Plinabulin reduced AKT and mTOR phosphorylation. Combined with the AKT/mTOR inhibitors LY294002 and rapamycin, plinabulin decreased p-mTOR and EGFR protein levels and increased cleaved-PARP levels. Plinabulin induces autophagy, and using an autophagy inhibitor enhances plinabulin-induced cell apoptosis. This suggests that plinabulin might trigger cytoprotective autophagy in glioblastoma cells. These findings indicate that plinabulin hinders glioblastoma growth and induces protective autophagy via the PI3K/AKT/mTOR pathway. Additionally, plinabulin combined with erlotinib showed greater cytotoxic efficacy than either drug alone in glioblastoma cells in vitro.ConclusionOur study provides new insights into the efficacy of plinabulin against glioblastoma and highlights the potential clinical utility of combining plinabulin with EGFR inhibitors as a chemotherapy strategy.

02 Oct 2024·Journal of Agricultural and Food Chemistry

High-Throughput Image-Based Assay for Identifying In Vitro Hepatocyte Microtubule Disruption

Article

Author: Lehman, Audrey ; Bowling, Andrew J. ; Johnson, Kristina ; Li, Yang ; Breitweiser, Lori A. ; Sherer, Eric ; Chen, Wei ; LaRocca, Jessica ; Pence, Heather E.

Disruption of microtubule stability in mammalian cells may lead to genotoxicity and carcinogenesis. The ability to screen for microtubule destabilization or stabilization is therefore a useful and efficient approach to aid in the design of molecules that are safe for human health. In this study, we developed a high-throughput 384-well assay combining immunocytochemistry with high-content imaging to assess microtubule disruption in the metabolically competent human liver cell line: HepaRG. To enhance analysis throughput, we implemented a supervised machine learning approach using a curated training library of 180 compounds. A majority voting ensemble of eight machine learning classifiers was employed for predicting microtubule disruptions. Our prediction model achieved over 99.0% accuracy and a 98.4% F1 score, which reflects the balance between precision and recall for in-sample validation and 93.5% accuracy and a 94.3% F1 score for out-of-sample validation. This automated image-based testing can provide a simple, high-throughput screening method for early stage discovery compounds to reduce the potential risk of genotoxicity for crop protection product development.

News (Medical) associated with Plinabulin

06 Mar 2025

·www.prnewswire.com

TEPMETKO Continues to Strengthens its Position as a Leading METex14 Skipping NSCLC Therapy | DelveInsight

With increasing biomarker-driven cancer treatments, TEPMETKO benefits from growing adoption in precision oncology. Competition from other MET inhibitors like TABRECTA (capmatinib) exists, but TEPMETKO's once-daily dosing and efficacy profile offer differentiation. LAS VEGAS, March 6, 2025 /PRNewswire/ -- DelveInsight's " TEPMETKO Market Size, Forecast, and Market Insight Report" highlights the details around TEPMETKO, a kinase inhibitor indicated for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of TEPMETKO. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. EMD Serono's TEPMETKO (tepotinib) Overview TEPMETKO is a kinase inhibitor prescribed for adult patients with metastatic non-small cell lung cancer (NSCLC) carrying MET exon 14 skipping alterations. The active component is Tepotinib (as hydrochloride monohydrate), administered orally. Patients should be cautioned about the heightened risk of severe or fatal interstitial lung disease/pneumonitis, liver toxicity, and potential embryo-fetal toxicity, necessitating effective contraception during and shortly after treatment. Tepotinib specifically targets MET, including variants with exon 14 skipping mutations. It blocks HGF-dependent and independent MET phosphorylation, disrupting MET-driven signaling pathways. Additionally, at clinically relevant concentrations, Tepotinib inhibits melatonin 2 and imidazoline 1 receptors. In vitro studies show that it suppresses tumor cell proliferation, anchorage-independent growth, and migration of MET-dependent cancer cells. In mouse models with MET-driven tumors, including those with MET exon 14 skipping alterations, Tepotinib reduced tumor growth, sustained MET phosphorylation inhibition, and, in one case, decreased metastasis formation. The recommended dose of TEPMETKO is 450 mg taken orally once daily until disease progression or intolerable toxicity occurs. Patients should take it at the same time each day, swallowing tablets whole without chewing, crushing, or splitting them. If a dose is missed and less than eight hours remain until the next scheduled dose, patients should skip it. In cases of vomiting after taking TEPMETKO, the next dose should be taken at the usual time. Learn more about TEPMETKO projected market size for NSCLC @ TEPMETKO Market Potential Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for 81% of all diagnosed cases. Early detection greatly improves outcomes, but diagnosing NSCLC and other lung cancers is challenging because their symptoms are often mistaken for common illnesses or the long-term effects of smoking. Consequently, 80% of NSCLC cases are already at advanced stages by the time they are identified, making treatment more difficult. Around 80% of EGFR mutations in NSCLC involve either exon 19 deletions or the exon 21 L858R substitution, both of which are classified as sensitizing mutations. Until the last decade, chemotherapy was the primary treatment for advanced and metastatic lung cancer. However, this changed in 2015 with the approval of the first immune checkpoint inhibitor (ICI), KEYTRUDA (pembrolizumab), as a second-line therapy for advanced cases. This was followed by TECENTRIQ (atezolizumab) in 2016. Both therapies were later approved for first-line treatment, broadening their use to a larger patient population. In 2020, the combination of OPDIVO (nivolumab) and ipilimumab also received approval as a first-line treatment for metastatic NSCLC. According to DelveInsight, the NSCLC market size across the 7MM is projected to grow from USD 30 billion in 2024, with a substantial CAGR through 2034. This growth is largely driven by the introduction of emerging therapies during the forecast period (2025–2034). Discover more about the NSCLC market in detail @ Non-small Cell Lung Cancer Market Report Emerging Competitors of TEPMETKO The NSCLC pipeline is very robust with the promising therapies such as Telisotuzumab vedotin (AbbVie), Patritumab deruxtecan (Daiichi Sankyo/AstraZeneca), Datopotamab deruxtecan (Daiichi Sankyo/AstraZeneca), Eftilagimod alpha (Immutep), BNT311/GEN1046 (acasunlimab) (Genmab), V940 (mRNA-4157) + Pembrolizumab (Moderna Therapeutics/Merck), Plinabulin + Docetaxel (BeyondSpring), Olomorasib (LY3537982) (Eli Lilly and Company), Zipalertinib (Cullinan Oncology/Taiho Pharma), Ceralasertib (AZD6738) (AstraZeneca), TEDOPI (EP-2101; IDM 2101; OSE-2101) (OSE Immuno-therapeutics), Sigvotatug vedotin (PF08046047) (Pfizer), ANKTIVA (N-803) (ImmunityBio), Aumolertinib/Almonertinib/HS-10206 (Jiangsu Hansoh Pharmaceutical), Niraparib (GSK), Savolitinib (AstraZeneca/Hutchison MediPharma), TRODELVY (Gilead Sciences), Pyrotinib (Jiangsu HengRui Medicine), Ociperlimab (BGB-A1217) (BieGene), Volrustomig (AstraZeneca), Gotistobart (BNT316/ONC-392) (OncoC4/BioNTech), Ivonescimab (AK112/SMT112) (Akeso Biopharma/Summit Therapeutics), ZYNYZ (retifanlimab/INCMGA00012) (Incyte/Macrogenics), Divarasib (GDC-6036) (Roche/Genentech), Tiragolumab (RG6058) (Roche), Sacituzumab Tirumotecan (Merck and Kelun-Biotech), JEMPERLI (dostarlimab/TSR-042) (GSK and AnaptysBio), Zongertinib (BI-1810631) (Boehringer Ingelheim), BAY 2927088 (Bayer), Serplulimab (HLX10) (Shanghai Henlius Biotech), Rilvegostomig (AZD2936) (AstraZeneca), MK-1084 (Merck, Taiho Pharmaceutical, and Astex), Domvanalimab (Arcus Biosciences and Gilead Sciences), OPDUALAG (nivolumab and relatlimab) (Bristol-Myers Squibb), Belrestotug + JEMPERLI (iTeos Therapeutics and GSK), Firmonertinib (ArriVent BioPharma), Sunvozertinib (DZD9008) (Dizal Pharmaceutical), Cobolimab (GSK), Livmoniplimab (AbbVie), Fianlimab (REGN3767) (Regeneron Pharmaceuticals), BNT327/PM8002 (Biotheus/BioNTech), HS-20117 (Hansoh BioMedical), IO102-IO103 + Pembrolizumab (IO Biotech), Naptumomab estafenatox (NeoTX Therapeutics/Active Biotech), FF-10832 (FUJIFILM Corporation), BNT116 (BioNTechSE/Regeneron Pharmaceuticals), CAN-2409 (Candel Therapeutics), Mecbotamab Vedotin (BA3011/CAB-AXL-ADC) (BioAtla), Bemcentinib (BGB 324/BGB-3234/R-428) (BerGenBio/Rigel Pharmaceuticals), DOVBLERON (taletrectinib/AB-106/IBI-344) (Nuvation Bio/Innovent Biologics/Daiichi Sankyo/Nippon Kayaku), Lifileucel (Iovance Biotherapeutics), IBI363 (Innovent Biologics), Sotevtamab (AB-16B5) (Alethia Biotherapeutics), Avutometinib (VS6766) (Verastem Oncology), Vebreltinib (APL-101) (Apollomics), LP-300 (Lantern Pharma), JNJ-90301900 (Johnson & Johnson Innovative Medicine), AMG 193 (Amgen), Luveltamab tazevibulin (Sutro Biopharma), PRT3789 (Prelude Therapeutics), Disitamab vedotin (Seagen), PADCEV (enfortumab vedotin) (Astellas Pharma), RP1 (Replimune), TIVDAK (tisotumab vedotin) (Seagen), Zanidatamab (Jazz Pharmaceuticals), Utidelone injectable (UTD1) (Beijing Biostar Pharmaceuticals), REGN5093-M114 (Regeneron Pharmaceuticals), SLC-391 (SignalChem Lifesciences), fulzerasib (GenFleet), Davutamig (REGN5093) (Regeneron Pharmaceuticals), TAS3351 (Taiho Oncology), H002 (RedCloud Bio), JIN-A02 (J INTS BIO), FWD1509 (Forward Pharma), Sabestomig (AZD7789) (AstraZeneca), Sasanlimab (Pfizer), Selvigaltin (GB1211) (Galecto Biotech), Vepafestinib Helsinn (Healthcare/Taiho Pharmaceutical), EP0031 (A400/ KL590586) (Ellipses Pharma/Kelun-Biotech), Pamvatamig (MCLA-129) (Merus), Zidesamtinib (NVL-520) (Nuvalent), NVL-655 (Nuvalent), RMC-4630 (Revolution Medicines), REQORSA (quaratusugene ozeplasmid) (Genprex), PDC*lung01 (PDC*line Pharma), Evalstotug (BA3071) (BioAtla and BeiGene), PT-112 (Promontory Therapeutics), MRT-2359 (Monte Rosa Therapeutics), GAIA-102 (GAIA BioMedicine), Rigosertib (Traws Pharma), HMBD-001 (Hummingbird Bioscience), PLB1004 (Avistone Biotechnology), ANS03 (Avistone Biotechnology), MYTX-011 (Mythic Therapeutics), A166 (Sichuan Kelun-Biotech Bio-pharmaceutical), Atamparib (BN-2397) (Ribon Therapeutics), DELTACEL (KB-GDT-01) (Kiromic BioPharma), Carotuximab (ENV-105) (Kairos Pharma), YL202 (MediLink Therapeutics), and others. To know more about the number of competing drugs in development, visit @ TEPMETKO Market Positioning Compared to Other Drugs Key Milestones of TEPMETKO In February 2024, the FDA granted traditional approval to TEPMETKO for adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. In February 2022, the EC approved TEPMETKO as monotherapy for the treatment of adult patients with advanced NSCLC harboring alterations leading to METex14 skipping who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy. In February 2021, Merck announced that the US FDA has approved TEPMETKO following priority review for the treatment of adult patients with metastatic NSCLC harboring MET exon 14 skipping alterations. This indication was approved under accelerated approval based on ORR and DOR. In October 2020, TEPMETKO received ODD for treating NSCLC with MET genomic tumor aberrations In March 2020, EMD Serono (the biopharmaceutical business of Merck KGaA), announced that the MHLW approved TEPMETKO for the treatment of patients with unresectable, advanced, or recurrent NSCLC with METex14 skipping alterations. In September 2019, the US FDA granted BTD for tepotinib in patients with metastatic NSCLC harboring METex14 skipping alterations who progressed following platinum-based cancer therapy Discover how TEPMETKO is shaping the NSCLC treatment landscape @ TEPMETKO NSCLC TEPMETKO Market Dynamics TEPMETKO competes in a growing but highly specialized market where MET-targeted therapies are gaining traction due to their efficacy in addressing MET-altered tumors. The market for MET inhibitors is expanding as precision oncology advances and molecular diagnostics become more widely available, enabling better identification of patients who would benefit from targeted treatments like TEPMETKO. A key factor shaping TEPMETKO's market dynamics is competition. It directly competes with Novartis' TABRECTA (capmatinib), another MET inhibitor approved for the same indication. While TEPMETKO offers the advantage of once-daily dosing compared to TABRECTA's twice-daily regimen, both drugs have similar efficacy profiles, making physician and patient preference an important differentiator. Additionally, broader competition from next-generation MET inhibitors and combination therapies in clinical trials could impact TEPMETKO's long-term market position. Regulatory approvals and market access play a crucial role in TEPMETKO's adoption. The drug has been approved in multiple regions, including the U.S., Europe, and Japan, but reimbursement and pricing strategies vary by market. Payer policies, along with the cost-benefit analysis of MET inhibitors compared to other targeted therapies, influence prescription trends. Furthermore, real-world evidence and post-marketing studies will be critical in demonstrating TEPMETKO's sustained effectiveness and safety, which could support expanded indications and increased market penetration. Looking ahead, the MET inhibitor market is expected to grow with advances in biomarker-driven therapy, further refining patient selection. TEPMETKO's success will depend on continued clinical development, potential label expansions, and strategic partnerships to strengthen its competitive edge. As new entrants emerge, Merck KGaA's ability to differentiate TEPMETKO through combination strategies or enhanced formulations may determine its long-term sustainability in this evolving landscape. Dive deeper to get more insight into TEPMETKO's strengths & weaknesses relative to competitors @ TEPMETKO Market Drug Report Table of Contents Related Reports Non-small Cell Lung Cancer Market Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key NSCLC companies including Daiichi Sankyo, AstraZeneca, Gilead Sciences, BieGene, AbbVie, Roche, Merck, Novartis, Pfizer, Takeda Pharmaceuticals, Eli Lilly, BerGenBio, GlaxoSmithKline, Duality biologics, among others. Non-small Cell Lung Cancer Pipeline Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key non-small cell lung cancer companies, including BridgeBio Pharma, Daiichi Sankyo, EMD Serono, Merck, BridgeBio Pharma, Abbvie, Pfizer, Eli Lilly and Company BioNTech SE, Shenzhen TargetRx, Taiho Pharmaceutical, Chong Kun Dang, Bristol Myers Squibb, Innovent Biologics, Xuanzhu Biopharmaceutical, Bayer, GeneScience Pharmaceuticals, InventisBio, Apollomics, Imugene, Ono Pharmaceutical, Pierre Fabre, Jiangsu Hengrui Medicine Co., Bristol-Myers Squibb, Surface Oncology, Inhibrx, Sinocelltech, Mirati Therapeutics, REVOLUTION Medicines, Yong Shun Technology Development, Iovance Biotherapeutics, Galecto Biotech, among others. C-MET Metastatic Non-small Cell Lung Cancer Market C-MET Metastatic Non-small Cell Lung Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key C-MET mNSCLC companies, including Novartis, Merck, EMD Serono, AbbVie, Regeneron Pharmaceuticals, Mythic Therapeutics, Apollomics, Johnson & Johnson Innovation, Haihe Biopharma, among others. C-MET Non-small Cell Lung Cancer Pipeline C-MET Non-small Cell Lung Cancer Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key C-MET non-small cell lung cancer companies, including AbbVie, Janssen Research & Development, Beijing Pearl Biotechnology Limited Liability Company, Novartis, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalImmunotherapyPriority Review

30 Jan 2025

·www.globenewswire.com

SEED Receives FDA Rare Pediatric Disease and Orphan Drug Designations for Lead Oncology Asset RBM39 Degrader and Enters Strategic Transactions with New Investors

Jan. 28, 2025 -- SEED Therapeutics Inc. (“SEED”), a biotechnology company pioneering the discovery of molecular glues for targeted protein degradation (TPD) using its proprietary RITE3™ platform, today announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease and Orphan Drug designations to SEED’s ST-01156 molecular glue. This novel agent degrades RBM39, an RNA splicing factor implicated in multiple mechanism-targeted solid tumor indications. SEED is advancing ST-01156 toward an Investigational New Drug (IND) application, with an expected IND filing in the first half of 2025. The Rare Pediatric Disease designation positions SEED to potentially receive an FDA priority review voucher upon approval of ST-01156. SEED also announced that its largest shareholder, BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring”), has entered into definitive agreements to sell a portion of its Series A-1 Preferred Shares of SEED. Upon completion of the transactions, BeyondSpring is expected to retain approximately 14.4% of SEED’s outstanding shares. “SEED is rapidly transitioning into a clinical-stage company, with the planned IND filing in the next few months for ST-01156, our novel and potentially best-in-class RBM39 degrader. This marks a significant milestone in our four-year journey to bring innovative therapies to patients,” said Dr. Lan Huang, Co-Founder, Chairman, and CEO of SEED and BeyondSpring. “RBM39 is a validated target to address cancers with high unmet medical needs, as highlighted in a recent Nature Reviews Drug Discovery article. At SEED, we are committed to improving patient outcomes through pioneering science and rational drug development.” “The FDA’s Rare Pediatric Disease and Orphan Drug designations for ST-01156 represent an important milestone, recognizing its potential to address significant unmet needs in rare oncology indications,” said Jackson Tai, Board Member of SEED. “These designations may help expedite and reduce the cost of developing, approving, and commercializing this therapeutic agent.” Tai added: “The transactions announced today will diversify SEED’s shareholder base. We believe this is a key step in ensuring that our capital structure and ownership distribution align with institutional investor expectations. SEED is now better positioned to pursue key initiatives, including advancing its clinical pipeline, extending its capital markets options, and maintaining its leadership in the field of targeted protein degradation.” SEED Therapeutics is an innovative biotech company focused on discovering and developing targeted protein degradation (TPD) therapeutics, with the mission to transform the treatment of diseases that currently have limited or no treatment options. Leveraging its cutting-edge RITE3™ platform, SEED is at the forefront of molecular glue-based TPD, addressing diseases in oncology and neurodegeneration. Through active collaborations with Eli Lilly and Company and Eisai Co., Ltd., and backed by a comprehensive intellectual property portfolio, SEED has built a robust pipeline of novel drug candidates now approaching clinical development. Visit www.seedtherapeutics.com to learn more. BeyondSpring is a global clinical-stage biopharmaceutical company advancing innovative therapies to improve clinical outcomes for patients with high unmet medical needs. BeyondSpring is advancing its first-in-class lead asset, Plinabulin, into late-stage clinical development as a direct anti-cancer agent in non-small cell lung cancer (NSCLC) and other cancer indications. Plinabulin binds to a differentiated pocket in tubulin, distinct from other tubulin binders, and is a potent inducer of dendritic cell maturation, which activates both adaptive and innate immunity. In combination with docetaxel, Plinabulin has demonstrated significant overall survival benefits compared to docetaxel alone in second- and third-line NSCLC with EGFR wild type (Lancet Respir Med 2024). Additionally, Plinabulin has shown a significant reduction in severe neutropenia across multiple clinical studies. BeyondSpring’s pipeline also includes three preclinical immuno-oncology assets. Visit www.beyondspringpharma.com for more information. The content above comes from the network. if any infringement, please contact us to modify.

Orphan Drug

11 Nov 2024

·www.globenewswire.com

BeyondSpring Presents Updated Efficacy Results from a Phase 2 IIT Study of Triple IO Combo of Pembrolizumab plus Plinabulin/Docetaxel in Metastatic NSCLC after Progressing on Prior Immune Checkpoint Inhibitors at the 39th SITC Annual Meeting

In 30 metastatic NSCLC patients who progressed on PD-1/PD-L1 inhibitors, the triple IO combo regimen at median follow-up time of 11.5 months achieved a DCR of 89.3% and Median PFS of 8.6 monthsFLORHAM PARK, N.J., Nov. 11, 2024 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, today announced that phase 2 IIT (Investigator-initiated) data on the first 30 patients dosed with plinabulin in the 303 Study of patients with non-small cell lung cancer (NSCLC) after disease progression on PD-1/PD-L1 inhibitors with and without chemotherapy were presented at the 39th Society for Immunotherapy of Cancer's (SITC) Annual Meeting on November 8th, 2024 in Houston, Texas. Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations who progress on immune checkpoint inhibitors (ICI) with and without standard chemotherapy. In the recent TROPION Lung-01 phase 3 studies, a similar patient population had an overall response rate (ORR) of 12.8% and median PFS (mPFS) of 3.7 months. 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 updated results from 30 patients. At the database lock on 29 August 2024, 36 patients were enrolled, 30 exposed to the plinabulin regimen. Prior to entry, all patients had experienced disease progression after initial clinical benefit with ICI. Of the 30 treated patients (median age at 68.0 years; ranged 50-77 years), 73.3% were male and 26.7% were female; 60% were current or former smokers. Histology included 57% patients (n=17) with non-squamous cell carcinoma and 43% (n=13) with squamous cell carcinoma. The median follow-up was 11.5 months. Below is an efficacy summary table: Primary Endpoint Plinabulin + Pembrolizumab + Docetaxel (n=30)Confirmed ORR (RECIST 1.1)21.1%Secondary Endpoints Median PFS (RECIST 1.1)8.6 MMedian OS (Overall Survival)Not reachedMedian DoR (Duration of Response)11.4 MDisease Control Rate(PR + SD > 4 months)89.3%(25/28 – 2 patients withdrew after first dose) The combination was generally well tolerated. 46.7% of patients experienced grade 3 or higher treatment-related adverse effects. Most common AE is myelosuppression (13.3%), GI side effect (13.3%), and transient hypertension (6.7%). There were no treatment-related deaths.Results are consistent with the data reported on the first 19 patients in Study 303 at ESMO in September. “Plinabulin is a potent inducer of dendritic cell or DC maturation that leads to T cell activation. DCs are 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 alteration or T cell exhaustion. Compared to historical controls of 3-4 months of median PFS2, the efficacy data with 30 patients maintained a doubled median PFS at 8.6 months, coupled with an impressive disease control rate of almost 90%, which continues to be encouraging and clinically meaningful for this severe unmet need,” said Dr. Mengzhao Wang, principal investigator at Peking Union Medical College Hospital. SITC 2024 Abstract Title: Phase 2 Study of Pembrolizumab (pemb) plus Plinabulin (plin) and Docetaxel (doc) for Metastatic NSCLC after Failure on First-line Immune Checkpoint Inhibitor Alone or Combination Therapy: Updated Efficacy and Safety Results on Immune Re-sensitization Presenting Author: Dr. Yan Xu, Peking Union Medical College HospitalAbstract Number: 1491 References: Schoenfeld et al. 2022, Lancet Oncology 23:279-291Ahn et al. 2024, TROPION Lung-01 Study, Journal of Clinical Oncology, https://doi.org/10.1200/JCO-24-0154 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. Around 800 patients have been treated with plinabulin with good tolerability. About 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. 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. Investor Contact:IR@beyondspringpharma.com Media Contact:PR@beyondspringpharma.com

Clinical ResultPhase 2ImmunotherapyPhase 3

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neutropenia	Preclinical	China	Dalian Wanchun Biotechnology Co. Ltd.Startup	17 Aug 2021
Neutropenia	Preclinical	China	Pharmaceutics International, Inc.	17 Aug 2021
Neutropenia	Preclinical	China	BeyondSpring Pharmaceuticals, Inc.	17 Aug 2021
Non-Small Cell Lung Cancer	Preclinical	China	Dalian Wanchun Biotechnology Co. Ltd.Startup	29 May 2018
Advanced Lung Non-Small Cell Carcinoma	Preclinical	United States	Pharmaceutics International, Inc.	30 Nov 2015
Advanced Lung Non-Small Cell Carcinoma	Preclinical	United States	BeyondSpring Pharmaceuticals, Inc.	30 Nov 2015
Advanced Lung Non-Small Cell Carcinoma	Preclinical	Australia	BeyondSpring Pharmaceuticals, Inc.	30 Nov 2015
Advanced Lung Non-Small Cell Carcinoma	Preclinical	Australia	Dalian Wanchun Biotechnology Co., Ltd.	30 Nov 2015
Advanced Lung Non-Small Cell Carcinoma	Preclinical	United States	Dalian Wanchun Biotechnology Co., Ltd.	30 Nov 2015
Advanced Lung Non-Small Cell Carcinoma	Preclinical	Australia	Pharmaceutics International, Inc.	30 Nov 2015

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03575793 (BTCRC-LUN17-127, CTgov)	Phase 1/2	Recurrent Lung Small Cell Carcinoma	39	Ipilimumab+Nivolumab+Plinabulin	qoqshuybmi(stpnrqjdlx) = keegvrbkeh lctaxzjshx (qhhgxysspg, hxiircnwuf - rwlbcclauu)	-	12 Nov 2024
NCT02504489 (DUBLIN-3, ESMO2024 \| Pubmed) Manual	Phase 3	Non-Small Cell Lung Cancer Second line \| Third line EGFR wild-type	559	Plinabulin+Docetaxel	(cyefqiaqbg) = akbpxlbqoo ztdubqazmr (cfnmrfitfy, 9.34 - 11.87) View more	Positive	14 Sep 2024
				Placebo+Docetaxel	(cyefqiaqbg) = gmwftlnnmj ztdubqazmr (cfnmrfitfy, 8.38 - 10.68) View more
NCT03102606 (PROTECTIVE-1 \| Study 105 \| BPI-2358-105, CTgov)	Phase 3	Chemotherapy-Induced Febrile Neutropenia \| Solid tumor \| Metastatic breast cancer \| metastatic non-small cell lung cancer \| Metastatic castration-resistant prostate cancer	105	D5W Placebo (Docetaxel (75 mg/m2) + Pegfilgrastim (6 mg) + Placebo Matching Plinabulin)	(fisaxlywcc) = aiyopgskxx bgtjaqqctc (bklhntevlc, stkdhecmyw - vdebjwkhgt) View more	-	29 Aug 2024
				Saline Placebo+Plinabulin (Docetaxel (75 mg/m2) + Plinabulin (40 mg) + Placebo Matching Pegfilgrastim)	(fisaxlywcc) = wtyyrjuzpw bgtjaqqctc (bklhntevlc, hhzzkiiajg - qeppaoajlb) View more
NCT04345900 (CTgov)	Phase 2	Chemotherapy-Induced Febrile Neutropenia \| Solid tumor \| metastatic non-small cell lung cancer	55	Pegfilgrastim+Docetaxel (Arm 1)	(kogqyozyty) = suivuefgzu dwifsmuvtz (lpijykyqme, fvsdwisjue - acmyoeqdac) View more	-	16 May 2024
				Plinabulin+Docetaxel (Arm 2)	(kogqyozyty) = jaddcajeod dwifsmuvtz (lpijykyqme, akrdgdzxuw - ehyrejtqgv) View more
EHA2024	Not Applicable	-	-	Plinabulin	cjqdaknntk(qlxejldlif) = towyarmyne eveqolzycq (rqzkbabmwf )	Positive	14 May 2024
				Selumetinib	cjqdaknntk(qlxejldlif) = oiehfexldp eveqolzycq (rqzkbabmwf )
IMS2023	Not Applicable	Multiple Myeloma	15	Plinabulin + pegfilgrastim	aopljtdleh(wlyyjocyyy) = qakypixjpc hpfbgqmwsk (cpiwzcujrt ) View more	-	26 Sep 2023
NCT02504489 (ASCO2023) Manual	Phase 2/3	Non-Small Cell Lung Cancer	-	Plinabulin+Docetaxel	(qjzvkngatj) = With Plin, AE frequency of diarrhea was slightly higher (5.2% vs 1%; 1 Gr4 case with Plin), but was manageable, and so was hypertension (11.2% vs 1.7%; all Gr3 cases) vs Plac. Hypertension occurred around the time of infusion and was short-lasting (~2-4 hours) and typically self-limiting. Plin had less AEs of neutropenia (16.4% vs 50.3%) and leukopenia (15.5% vs 38.5%) vs Plac. lrbspuxuvg (ekzfpitjwm )	Positive	31 May 2023
				Placebo+Docetaxel
NCT03102606 (PROTECTIVE-1, SABCS2023)	Phase 3	Chemotherapy-Induced Febrile Neutropenia \| Solid tumor \| Metastatic breast cancer \| metastatic non-small cell lung cancer \| Metastatic castration-resistant prostate cancer NCCN high FN risk factor	27	Plinabulin	baviihygli(ftpohxoqvt) = Plin was superior vs No-Treatment for Doc-induced neutropenia and HC, while maintaining QoL and with minimal AE and bone pain burden smhtfneknp (ggithitsjj ) View more	Positive	01 Mar 2023
NCT03102606 (PROTECTIVE-1, ESMO_ASIA2022)	Phase 2/3	Non-Small Cell Lung Cancer	30	Plinabulin	wymfutirdb(ordzhgncrv) = gsargkevlh etojrbpvue (tlitlrxzqx )	Positive	03 Dec 2022
NCT03294577 (PROTECTIVE-2, Corporate Publications) Manual	Phase 3	Neutropenia	115	Pegfilgrastim+Plinabulin	(jgvpyrqvvi) = kqouzcncxi ojukamncgo (ymqjidxjog )	Positive	21 Oct 2022
				Pegfilgrastim	(jgvpyrqvvi) = ynasbbklli ojukamncgo (ymqjidxjog )

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