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.

开始日期2023-11-01

申办/合作机构

华中科技大学同济医学院附属协和医院

NCT05599789 / Recruiting临床2期IIT

A Phase 2 Study of Pembrolizumab in Combination With Plinabulin and Docetaxel in Previously Treated Patients With Metastatic Non-Small Cell Lung Cancer and Progressive Disease (PD) After Immunotherapy (Anti-PD-1/PD-L1 Inhibitor) Alone or in Combination With Platinum-doublet Chemotherapy (KeyPemls-004)

A Phase 2 Study of Pembrolizumab in Combination with Plinabulin and Docetaxel in previously treated Patients with Metastatic Non-Small Cell Lung Cancer and progressive disease (PD) after immunotherapy (Anti-PD-1/PD-L1 inhibitor) alone or in combination with Platinum-doublet Chemotherapy.

开始日期2023-02-01

申办/合作机构

北京协和医院

[+2]

NCT05130827 / Active, not recruiting临床2期IIT

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).

开始日期2021-12-21

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

100 项与普那布林相关的临床结果

登录后查看更多信息

100 项与普那布林相关的转化医学

登录后查看更多信息

100 项与普那布林相关的专利（医药）

登录后查看更多信息

项与普那布林相关的文献（医药）

2024-10-01·Lancet Respiratory Medicine

Plinabulin, a microtubule destabilising agent, in non-small-cell lung cancer: lessons from the DUBLIN-3 trial

Article

作者: Molina-Vila, Miguel Angel ; González-Cao, María ; Rosell, Rafael

2024-10-01·Lancet Respiratory Medicine

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

Article

作者: Huang, Lan ; Oliff, Ira ; Shunyakov, Leonid V ; Hu, Chunhong ; Wu, Yanping ; Han, Baohui ; Liu, Chunling ; Feinstein, Trevor ; Kloecker, Goetz ; Chen, Gongyan ; Zhao, Jun ; Feng, Jifeng ; Kalmadi, R Sujith ; Ye, Feng ; Guo, Qi-sen ; Thara, Eddie ; Jennens, Ross ; Jiang, Da ; Li, Helen ; Pan, Hongming ; Li, Xiaoling ; Liu, Bin ; Wang, Zhongkun ; Zhang, Yiping ; Du, Lihua ; Luo, Feng ; Wang, Huaqing ; Huang, Chao Hui ; Zhang, Liangming ; Kloecker, Goetz H ; Guo, Qi-Sen ; Jie, Zhijun ; Mao, Weidong ; Liu, Zhihua ; Wu, Huijuan ; Cao, Lejie ; Hrom, John S ; Lu, Junguo ; Nagrial, Adnan ; Shi, Yuankai ; Ruiz, Jimmy ; Lloyd, Ken ; Bazhenova, Lyudmila ; Sujith, Kalmadi R ; Zhou, Jian-ying ; Cheng, Ying ; Cheng, Gongyan ; Oliff, Ira A ; Wong, Matthew ; Yao, Yu ; Sun, Yan ; Kiberu, Andrew ; Jain, Vikram ; Karim, Nagla A ; Shi, Jianhua ; Mowat, Rex B

BACKGROUND:

There is an unmet need for second-line and third-line treatments that are effective and tolerable for advanced or metastatic non-small-cell lung cancer (NSCLC) with no driver mutations.

METHODS:

In this phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial, we enrolled patients from 58 medical centres in Australia, China, and the USA. Eligible patients were adults with epidermal growth factor receptor (EGFR) wild-type NSCLC who had progressed after first-line platinum-based therapy. Patients were randomly assigned (1:1) using an independent stratified randomisation schedule with a block size of four to receive intravenous docetaxel 75 mg/m² on day 1 and either plinabulin (30 mg/m²) or placebo on days 1 and 8 in 21-day cycles until progression, unacceptable toxic effects, withdrawal, or death. The primary endpoint was overall survival (OS) in the intention-to-treat (ITT) population. Safety was analysed in all patients who had received at least one dose of study drug or placebo. This trial is registered with ClinicalTrials.gov (NCT02504489) and is now closed.

FINDINGS:

Between Nov 30, 2015, and Jan 6, 2021, 919 patients were screened for inclusion. 360 patients were excluded, and 559 were enrolled and randomly assigned to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). 406 (73%) of 559 patients were male, 153 (27%) were female, and 488 (87%) were Asian. Median OS was 10·5 months (95% CI 9·34-11·87) in the plinabulin group compared with 9·4 months (8·38-10·68) in the control group (stratified HR 0·82, 95% CI 0·68-0·99; p=0·0399). Mean OS was 15·08 months (13·42-16·74) in the plinabulin group compared with 12·77 months (11·45-14·10) in the placebo group using restricted mean survival time analysis (difference 2·31 months, 95% CI 0·18-4·44; p=0·0332). Treatment-emergent adverse events occurred in 273 (>99%) of 274 patients in the plinabulin group and 276 (99%) of 278 patients in the control group. Grade 3 or 4 gastrointestinal disorders occurred more frequently in the plinabulin group than in the placebo group, with the most frequent being diarrhoea (24 [9%] of 274 patients vs three [1%] of 278) and vomiting (six [2%] vs one [<1%]), as did transient grade 3 hypertension (50 [18%] vs eight [3%]). Treatment-emergent death was reported in 12 patients (4%) in the plinabulin group and ten patients (4%) in the placebo group.

INTERPRETATION:

Plinabulin plus docetaxel significantly improved OS as second-line and third-line treatment in patients with advanced or metastatic EGFR wild-type NSCLC and could be considered as a new treatment option in this population.

FUNDING:

BeyondSpring Pharmaceuticals.

2024-09-01·BIOMATERIALS

Co-delivery of Plinabulin and Tirapazamine boosts anti-tumor efficacy by simultaneously destroying tumor blood vessels and killing tumor cells

Article

作者: Xu, Yajun ; Liu, Ya ; Tang, Zhaohui ; Sakurai, Kazuo ; Lv, Jianlin ; Yu, Haiyang

It is imperative to optimize chemotherapy for heightened anti-tumor therapeutic efficacy. Unrestrained tumor cell proliferation and sustained angiogenesis are pivotal for cancer progression. Plinabulin, a vascular disrupting agent, selectively destroys tumor blood vessels. Tirapazamine (TPZ), a hypoxia-activated prodrug, intensifies cytotoxicity in diminishing oxygen levels within tumor cells. Despite completing Phase III clinical trials, both agents exhibited modest treatment efficiency due to dose-limiting toxicity. In this study, we employed methoxy poly(ethylene glycol)-b-poly(_D,_L-lactide) (mPEG-b-PDLLA) to co-deliver Plinabulin and TPZ to the tumor site, concurrently disrupting blood vessels and eliminating tumor cells, addressing both symptoms and the root cause of tumor progression. Plinabulin was converted into a prodrug with esterase response (PSM), and TPZ was synthesized into a hexyl chain-containing derivative (TPZHex) for effective co-delivery. PSM and TPZHex were co-encapsulated with mPEG-b-PDLLA, forming nanodrugs (PT-NPs). At the tumor site, PT-NPs responded to esterase overexpression, releasing Plinabulin, disrupting blood vessels, and causing nutritional and oxygen deficiency. TPZHex was activated in response to increased hypoxia, killing tumor cells. In treating 4T1 tumors, PT-NPs demonstrated enhanced therapeutic efficacy, achieving a 92.9 % tumor suppression rate and a 20 % cure rate. This research presented an innovative strategy to enhance synergistic efficacy and reduce toxicity in combination chemotherapy.

141

项与普那布林相关的新闻（医药）

2024-11-23

·ioncology

2024 WCLC 晚期肺癌后线治疗进展合集

点上方蓝字“ioncology”关注我们，然后点右上角“…”菜单，选择“设为星标” 前言：2024年世界肺癌大会于9月7-10日在美国圣迭戈举行，《肿瘤瞭望》将会议口头汇报领域的部分重要结果编译，分享给读者，本期将聚焦晚期NSCLC患者后线治疗进展的口头汇报。替雷利珠单抗联合Sitravatinib在晚期且接受化疗及免疫检查点抑制剂耐药的非小细胞肺癌患者中的疗效及安全性：SAFFRON-301研究 01 对于驱动基因突变阴性的晚期非小细胞肺癌患者，化疗联合免疫是一线标准治疗，患者耐药后，二线标准治疗为多西他赛，但疗效有限。替雷利珠单抗是一款针对PD-1的免疫检查点抑制剂，Sitravatinib是一款多靶点抗血管生成药物，其涵盖的靶点包括了VEGFR2及TAM等。Ib期临床研究显示，替雷利珠单抗联合Sitravatinib显示了良好的抗肿瘤作用。本研究旨在进一步探索该治疗策略的疗效及安全性。这是一项随机对照临床研究，纳入组织病理学确认的非小细胞肺癌患者，患者驱动基因突变阴性，既往接受化疗联合免疫后疾病进展。符合入组标准的患者按1:1的比例随机分为多西他赛75 mg/m2或替雷利珠单抗(200 mg，每3周一次)联合Sitravatinib(100 mg，口服每日一次)，主要研究终点为OS及独立评审委员会评估的PFS。最终，联合治疗组和多西他赛组分别入组187例和190例患者，PD-L1＞1%的患者占比分别为36.4%和36.8%。独立评审委员会评估的中位PFS分别为4.4个月和2.9个月，HR=0.82。研究者评估的中位PFS分别为4.4个月和2.9个月，HR=0.64，两组中位OS分别为11.5个月和11.4个月，HR=1.02。亚组分析未发现潜在获益人群，两组ORR分别为12.3%和12.6%，DCR分别为69.5%和53.7%，3度以上全因不良反应发生率分别为65.1%和56.5%，严重不良反应发生率分别为44.6%和37.3%。两组OS数据基于不良的获益风险比，该研究被提前终止。 Dato-Dxd或多西他赛后线治疗非小细胞肺癌患者的疗效及安全性：TROPION-Lung-01研究最终OS分析 02 TROPION-Lung-01研究探索了Dato-Dxd后线与多西他赛的疗效及安全性。首次数据公布时，两组中位PFS分别为4.4个月和3.7个月，HR=0.75，P=0.004，本次公布了最终的OS数据。该研究纳入既往未接受过多西他赛治疗的局部晚期或转移性非小细胞肺癌患者，驱动基因突变阴性患者既往需接受化疗及免疫检查点抑制剂治疗，驱动基因突变阳性的患者需接受靶向治疗及含铂双药治疗。符合入组标准的患者按1:1的比例随机分为Dato-Dxd 6 mg/kg，每三周一次或多西他赛75 mg/m2，每三周一次，主要研究终点为独立评审委员会评估的PFS和OS。最终，两组分别入组299例和305例患者，基线特点均衡可比，基线分别有26%和30%的患者有脑转移，两组均有88%的患者既往接受过免疫治疗，分别有15%和16%的患者接受过靶向治疗。最终分析时，两组中位OS分别为12.9个月和11.8个月，HR=0.94，P=0.53。亚组分析未发现获益人群，非鳞、非小细胞肺癌患者，中位OS分别为14.6个月和12.3个月，HR=0.84，24个月OS率分别为29%和21.7%，鳞癌患者两组中位OS分别为7.6个月和9.4个月，HR=1.32，24个月OS率分别为14.8%和13.7%。3度以上治疗相关不良反应发生率分别为26%和42%，剂量降低发生率分别为20%和30%，因不良反应导致治疗永久终止的发生率分别为8%和12%。严重不良反应发生率分别为11%和13%。Dato-Dxd组最常见的3度及以上不良反应为口腔黏膜炎，占比7%；在化疗组最常见的为中性粒细胞降低，占比23%。两组OS数据更新后的数据显示了OS在数值上的获益，并但并没有统计学差异。普布林联合或不联合多西他赛二线或三线治疗铂类药物耐药的非小细胞肺癌患者：一项III期随机对照临床研究 03 普纳布林是一款免疫调节剂，本研究旨在探索该药联合多西他赛在后线治疗晚期非小细胞肺癌患者的疗效及安全性。研究纳入非鳞、非小细胞肺癌患者，患者既往接受过一种或两种含铂双药治疗后出现疾病进展，接受免疫检查点抑制剂治疗后耐药的患者允许入组。符合入组标准的患者按1:1的比例随机分为多西他赛单药75 mg/m2或进一步联合普布林30 mg/m2，第1、8天给药。主要研究终点为OS。最终，联合治疗组和单药组分别入组281例和278例患者，基线特点均衡可比，既往分别有20.3%和17.6%的患者接受过免疫检查点抑制剂治疗，分别有75.4%和73.4%的患者接受过一线治疗，两组中位OS分别为10.5个月和9.4个月，HR=0.82，P=0.0399，2年OS率分别为22.1%和12.5%，3年OS率分别为11.7%和5.3%。经过24个月随访后，两组中位OS分别为10.8个月和9.3个月，HR=0.81，P=0.027。中位PFS分别为3.3个月和2.8个月，HR=0.79，P=0.017，ORR分别为14%和9%，4度粒细胞缺乏发生率分别为5%和28%。两组OS 在多西他赛基础上联合普那布林给患者带来相应的生存获益，安全性可耐受。 Tusamitamab或多西他赛治疗非鳞、非小细胞肺癌患者的疗效及安全性：一项III期临床研究(CARMEN-LC-03研究) 04 CEACAM5广泛表达于肿瘤细胞表面，Tusamitamab是针对该靶点的抗体偶联药物，其偶联的细胞毒类药物为DM4。该研究纳入非鳞、非小细胞肺癌患者，既往接受化疗或免疫检查点抑制剂耐药后出现疾病进展，CEACAM5表达定义为在超过50%的细胞中表达超过2+。符合入组标准的患者按1:1的比例随机分为多西他赛75 mg/m2，每3周一次或Tusamitamab 100 mg/m2，每两周一次。主要研究终点为独立评审委员会评估的PFS和OS。最终，Tusamitamab组和多西他赛组分别入组225例和225例患者，两组患者基线特点均衡可比。CEACAM5表达在50~79%和≥50%的患者，分别为46.4% vs. 43.1%；53.6 vs. 56.9%。两组分别有17.5%和14.9%的患者既往接受过紫杉醇类药物治疗。独立评审委员会评估的中位PFS分别为5.4个月和5.9个月，HR=1.14，P=0.82。两组中位OS分别为12.8个月和11.5个月，HR=0.85，P=0.11。亚组分析未发现获益人群。 PFS及OS 两组3度及以上不良反应发生率分别为40.7%和57.6%。治疗相关3度以上不良反应发生率分别为14.9%和39.5%并分别导致了16.5%和36.2%的患者剂量降低，7.7%和16.9%的患者治疗永久性终止。戈沙妥珠单抗或多西他赛后线治疗转移性非小细胞肺癌患者：EVOKE-01研究免疫不响应患者的亚组分析 05 EVOKE-01研究探索了戈沙妥珠单抗这一针对TROP-2的ADC药物后线治疗晚期非小细胞肺癌患者的疗效及安全性，研究纳入含铂双药治疗及联合免疫检查点抑制剂治疗后耐药的晚期非小细胞肺癌患者，符合入组标准的患者按1:1的比例随机分为戈沙妥珠单抗10 mg/kg或多西他赛75 mg/m2，主要研究终点OS在前期已经报道，两组中位OS分别为11.1个月和9.8个月，HR=0.84，P=0.053。亚组分析显示，在前线对免疫检查点抑制剂不响应的患者，从戈沙妥珠单抗治疗中治疗获益，不响应和响应组的患者，HR分别为0.75和1.09。本研究详细报道了该组数据。不响应的患者共计383例，戈沙妥珠单抗组和多西他赛组分别有192例和191例，全组患者基线特点均衡可比且与ITT人群类似。不响应的患者中，19.8%和18.8%的患者接受免疫单药治疗。这部分患者的中位PFS分别为4.2个月和3.7个月，HR=0.88；中位OS分别为11.8个月和8.3个月，HR=0.75。疗效评估为SD的患者，两组中位OS分别为12.5个月和9.9个月，HR=0.79，评估为PD的患者，两组中位OS分别为10.8个月和7.0个月，HR=0.67。非鳞、非小细胞肺癌患者，两组中位OS分别为11.8个月和8.4个月，HR=0.79，鳞癌患者，两组中位OS分别为10.7个月和7.9个月，HR=0.62。免疫不响应患者的OS及PFS 3度以上不良反应发生率分别为67.7%和72.5%，严重不良反应发生率分别为48.7%和42.9%，并分别导致了8.5%和13.2%的患者治疗永久性终止。 D1553治疗KRAS G12C突变的非小细胞肺癌患者的疗效及安全性：一项II期临床研究的更新 06 D1553是一款针对KRAS G12C突变的非小细胞肺癌患者，该研究前期数据显示，该药后线治疗KRAS G12C突变的非小细胞肺癌患者展示了良好的抗肿瘤活性。本次公布了其长期随访数据。研究纳入免疫检查点抑制剂及含铂双药治疗后耐药的晚期非小细胞肺癌患者，患者携带KRAS G12C突变，符合入组标准的患者给予D1553 600 mg，口服，每日两次治疗，主要研究终点为独立评审委员会评估的ORR。研究共入组123例患者，数据截止日期时，22%的患者仍接受治疗，中位随访时间12.3个月。 ORR和DCR分别为52.0%和88.6%，中位DOR为12.5个月，中位至响应出现时间1.4个月，中位PFS和中位OS分别为9.1个月和14.1个月，12个月PFS率和OS率分别为36.4%和57.2%。患者的长期获益最常见的3度及以上治疗相关不良反应包括谷草转氨酶升高17.1%，谷丙转氨酶升高15.4%，γ-GT升高22.0%，因不良反应而导致剂量降低、治疗中断的患者占比分别为30.1%和41.5%。经过长期的随访数据，展示了D1553的长期获益。 IBI-351治疗KRAS G12C突变的非小细胞肺癌患者的疗效及安全性：一项II期临床研究 07 IBI-351是一款针对KRAS G12C突变的靶向治疗药物，本研究更新了其关键II期临床研究数据。该研究纳入KRAS G12C突变的晚期非小细胞肺癌患者，患者既往治疗线数小于等于3线。符合入组标准的患者接受IBI-351 600mg，口服，每日两次治疗，主要研究终点ORR。研究共纳入116例患者，基线30.2%的患者有脑转移，接受过PD-L1和化疗的患者占比分别为87.1%和97.4%，ORR为49.1%，DCR为90.5%。中位PFS为9.7个月，12个月的PFS率和OS率分别为37.9%和54.4%，3度以上治疗相关不良反应发生率为41.4%，因不良反应而导致治疗中断、剂量降低，治疗终止的患者分别为33.6%、6.9%和6.0%。患者的长期患者数据（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

临床结果

2024-11-12

·药明康德

近90%疾病控制率、持久缓解近1年！潜在“first-in-class"抗癌小分子积极数据公布

▎药明康德内容团队编辑 BeyondSpring今天公布研究者发起的临床2期试验KeyPelms-004的最新数据。分析显示，接受其在研小分子药物plinabulin、多西他赛（docetaxel）与PD-1抑制剂pembrolizumab三联疗法治疗的转移性非小细胞肺癌（NSCLC）患者的疾病控制率（DCR）近90%，且患者缓解持续近1年。试验详细数据公布于第39届癌症免疫治疗学会（SITC）年会当中。 KeyPelms-004（或303研究）是一项单组、开放标签的2期研究，旨在评估pembrolizumab加plinabulin与多西他赛三联疗法的疗效和安全性。入组前，所有NSCLC患者在对免疫检查点抑制剂（ICI）初始临床治疗产生应答后均出现疾病进展。截至2024年8月29日数据截止时，共招募了36名患者，其中30名接受了plinabulin三联疗法治疗。 ▲试验疗效结果摘要（图片来源：参考资料[1]）分析显示，在30名接受治疗的转移性NSCLC患者中，plinabulin三联疗法在中位随访时间为11.5个月时实现了89.3%的DCR和8.6个月的中位无进展生存期（PFS），患者的中位缓解持续时间（DoR）达11.4个月。此外，该药物组合通常耐受性良好。46.7%的患者经历了3级或更高级别的治疗相关不良反应。最常见的不良反应是骨髓抑制（13.3%）、胃肠道副作用（13.3%）和短暂性高血压（6.7%）。没有治疗相关死亡病例。 ▲Plinabulin化学结构（图片来源：PubChem） Plinabulin是一种新型、潜在“first-in-class"的树突状细胞成熟剂，也是一款靶向微管蛋白口袋的可逆性结合剂。Plinabulin不会改变微管蛋白动力学，或与像是多西他赛的微管蛋白稳定剂发生拮抗作用，因此与其他的微管结合剂相比，具有差异化的特性与良好耐受性。此外，plinabulin还可显著降低化疗引起的中性粒细胞减少症，从而提高多西他赛的耐受性。直至目前为止，约有800例患者接受了该疗法的治疗。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料： [1] 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. Retrieved November 11, 2024 from https://www.globenewswire.com/news-release/2024/11/11/2978241/0/en/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.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床2期临床结果

2024-11-11

·GlobeNewswire-Health Care

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

临床结果临床2期免疫疗法临床3期

100 项与普那布林相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D09655	普那布林	-	DB05992

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
中性粒细胞减少	申请上市	中国	Pharmaceutics International, Inc.	2021-08-17
中性粒细胞减少	申请上市	中国	BeyondSpring Pharmaceuticals, Inc.	2021-08-17
中性粒细胞减少	申请上市	中国	大连万春布林医药有限公司初创企业	2021-08-17
HER2 阴性乳腺癌	临床3期	中国	BeyondSpring Pharmaceuticals, Inc.	2019-10-23
HER2 阴性乳腺癌	临床3期	乌克兰	BeyondSpring Pharmaceuticals, Inc.	2019-10-23
续存性动脉干	临床3期	中国	BeyondSpring Pharmaceuticals, Inc.	2019-10-23
续存性动脉干	临床3期	乌克兰	BeyondSpring Pharmaceuticals, Inc.	2019-10-23
乳腺癌	临床3期	美国	Pharmaceutics International, Inc.	2019-10-15
乳腺癌	临床3期	美国	大连万春布林医药有限公司初创企业	2019-10-15
乳腺癌	临床3期	中国	Pharmaceutics International, Inc.	2019-10-15

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03575793 (BTCRC-LUN17-127, CTgov)	临床1/2期	复发性小细胞肺癌	39	Ipilimumab+Nivolumab+Plinabulin	艱壓鑰鬱鹹窪鹽積獵衊(窪膚願築憲艱鬱夢蓋艱) = 壓艱餘製網夢膚積簾觸鹹餘選觸選簾築築積膚 (構襯觸觸齋遞獵選鹹製, 鏇鹹醖遞製夢鑰製鏇膚 ~ 簾鏇顧襯夢製蓋衊簾廠)	-	2024-11-12
NCT02504489 (DUBLIN-3, ESMO2024) 人工标引	临床3期	非小细胞肺癌二线 \| 三线 EGFR wild-type	559	Plinabulin+Docetaxel	簾製選窪積窪衊窪餘夢(鏇積糧夢夢築衊膚範築) = 膚襯襯網蓋網襯醖齋製觸構壓淵鬱廠觸餘繭觸 (鹹鬱選積鑰遞膚餘築願 ) 更多	积极	2024-09-14
				Placebo+Docetaxel	簾製選窪積窪衊窪餘夢(鏇積糧夢夢築衊膚範築) = 壓淵築夢糧選夢製製壓觸構壓淵鬱廠觸餘繭觸 (鹹鬱選積鑰遞膚餘築願 ) 更多
NCT05599789 (ESMO2024) 人工标引	临床2期	转移性非小细胞肺癌二线	19	Pembrolizumab plinabulindocetaxel	(鹹繭網壓憲範積繭範簾) = 齋積築積淵壓選繭簾鬱積廠糧築齋鬱壓鏇網糧 (製積餘廠選選衊簾積襯 ) 更多	积极	2024-09-14
EHA2024	N/A	-	-	Plinabulin	鹽廠憲觸壓夢選鹽襯鹽(窪壓衊繭選顧遞獵艱壓) = 膚衊淵襯築繭獵淵壓鏇鏇網鑰繭艱襯夢鹹糧願 (膚廠積廠衊簾壓衊壓觸 )	积极	2024-05-14
				Selumetinib	鹽廠憲觸壓夢選鹽襯鹽(窪壓衊繭選顧遞獵艱壓) = 淵鹽製廠構膚觸選窪餘鏇網鑰繭艱襯夢鹹糧願 (膚廠積廠衊簾壓衊壓觸 )
IMS2023	N/A	多发性骨髓瘤	15	Plinabulin + pegfilgrastim	膚齋積製淵鹽鹹憲獵廠(積窪糧蓋廠積蓋鹹願簾) = 鹽遞艱構鑰衊鹹醖蓋鑰網鬱壓繭窪鹽夢築築糧 (廠願顧餘築襯構淵蓋鹽 ) 更多	-	2023-09-26
NCT02504489 (ASCO2023) 人工标引	临床2/3期	非小细胞肺癌	-	Plinabulin+Docetaxel	觸鹽醖繭鏇製願齋積網(餘顧構膚積淵鬱膚顧夢) = 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. 範觸範築顧襯憲廠鏇廠 (鏇遞積淵憲積鑰顧鹹齋 )	积极	2023-05-31
				Placebo+Docetaxel
NCT05130827 (Corporate Publications) 人工标引	临床2期	中性粒细胞减少 \| 多发性骨髓瘤	10	JZB-27+Plinabulin	鑰夢淵選壓鹹膚構願糧(鑰鹹願繭願鏇願鏇網觸) = 淵網衊餘壓簾憲鬱鏇願觸繭衊簾鏇壓鹹鑰範遞 (廠鑰築鬱遞築壓糧積壓 ) 更多	积极	2022-08-29
NCT02504489 (BPI-2358-103, ASCO2022) 人工标引	临床3期	非小细胞肺癌二线 EGFR Wild-type	361	Docetaxel+Plinabulin	鏇襯範糧顧積鑰鹹積衊(網顧夢窪製齋餘艱築顧) = 築構糧襯膚艱簾鹽艱積鬱艱壓艱餘憲膚選築範 (顧網繭鏇蓋製遞壓繭齋, 9.37 ~ 12.4) 更多	积极	2022-06-02
				Docetaxel+Placebo	鏇襯範糧顧積鑰鹹積衊(網顧夢窪製齋餘艱築顧) = 網淵範製範遞構窪簾獵鬱艱壓艱餘憲膚選築範 (顧網繭鏇蓋製遞壓繭齋, 8.05 ~ 10.9) 更多
PROTECTIVE-2 (CSCO2021)	临床3期	中性粒细胞减少	221	普那布林40mg+培非格司亭6mg	憲壓鑰廠壓鏇願製鑰鬱(艱壓糧築憲願廠遞壓繭) = 繭簾遞鑰獵襯衊鏇遞窪餘簾淵廠構鹽餘積壓鹹 (齋衊齋醖構鹹醖齋襯選 ) 更多	积极	2021-09-25
				培非格司亭6mg+安慰剂	憲壓鑰廠壓鏇願製鑰鬱(艱壓糧築憲願廠遞壓繭) = 網膚鏇衊膚願淵餘醖願餘簾淵廠構鹽餘積壓鹹 (齋衊齋醖構鹹醖齋襯選 ) 更多
PROTECTIVE-2(BPI-2358-106) (CSCO2021)	临床3期	伴有中性粒细胞减少的皮肤异色病	221	普那布林 40mg+培非格司亭 6mg	襯齋觸鬱淵齋簾廠觸範(餘衊築選鏇鹹網艱襯鑰) = 醖鬱遞製膚糧鬱範簾衊壓顧鬱壓觸願鬱鏇鑰廠 (製網淵壓鏇壓鑰艱鑰觸 ) 更多	-	2021-09-25
				培非格司亭 6mg+安慰剂	襯齋觸鬱淵齋簾廠觸範(餘衊築選鏇鹹網艱襯鑰) = 蓋範築壓製鹹積襯襯遞壓顧鬱壓觸願鬱鏇鑰廠 (製網淵壓鏇壓鑰艱鑰觸 ) 更多