Efficacy and Safety of Trifluridine/tipiracil (TAS-102) Combined with Bevacizumab and Putalimab in the Treatment of Patients with MCRC After Cytoreductive Surgery: a Single-arm, Single-center Clinical Study

Colorectal cancer (CRC) is one of the most common malignant tumors. With the rapid development of China's economy, people's living standards have been significantly improved, and lifestyles and dietary structures have changed. Smoking, drinking, high-fat, high-energy diets, etc. have led to an increase in the incidence of colorectal cancer year by year. Data show that in 2022, there will be 510,000 new cases of colorectal cancer in China, and about 240,000 deaths related to colorectal cancer. Radical surgery is the main initial treatment for early and middle-stage colorectal cancer and some metastatic colorectal cancer. Although the level of surgical treatment of colorectal cancer has been greatly improved and can achieve cure for some patients, its 5-year overall survival rate is only about 60%, and the main cause of death is distant metastasis and recurrence. In recent years, with the in-depth understanding of the treatment mechanism of metastatic colorectal cancer (mCRC), a variety of new treatment options have been proposed and applied in clinical practice in order to improve the quality of life of patients and prolong their survival.
Trifluridine/tipivirine (TAS-102) is a new type of cytotoxic drug that exerts anti-tumor effects by directly incorporating into DNA chains to destroy DNA function. Its mechanism of action is different from that of fluorouracil drugs, and it can resist 5-fluorouracil (5-FU) resistance, providing a new treatment option for mCRC patients. TAS-102 has been approved in China for mCRC patients who have previously received fluoropyrimidine, oxaliplatin, and irinotecan-based chemotherapy, as well as those who have previously received or are not suitable for anti-vascular endothelial growth factor (VEGF) therapy and anti-epidermal growth factor receptor (EGFR) therapy (RAS wild type). Bevacizumab, as a monoclonal antibody targeting VEGF, exerts its anti-tumor effect by inhibiting tumor angiogenesis. Putlimumab, as an immune checkpoint inhibitor, enhances the body's immune response to tumors by blocking the PD-1/PD-L1 signaling pathway.
Combination therapy has attracted much attention due to its possible synergistic effect. Studies have shown that TAS-102 combined with bevacizumab can achieve longer overall survival (OS) than TAS-102 monotherapy. In addition, TAS-102 combined with bevacizumab for refractory mCRC has also been approved by the FDA, showing its potential and importance in the treatment of mCRC. Therefore, this study aims to explore the efficacy and safety of TAS-102 combined with bevacizumab and putelimab in patients with mCRC after cytoreductive surgery, in order to provide a more effective treatment for mCRC patients. Through the design of a single-arm, single-center clinical study, we can have a deeper understanding of the efficacy and safety of this combined treatment in a specific patient population, providing a scientific basis for future clinical applications.

开始日期2025-05-01

申办/合作机构

浙江大学医学院附属第二医院（浙江省第二医院）

NCT06872606

/ Not yet recruiting临床2期IIT

The Efficacy and Safety of Short-Course Radiotherapy Combined with Intracavitary Brachytherapy Followed by Pucotenlimab, Bevacizumab, Oxaliplatin, and Trifluridine/Tipiracil (TAS-102) for Total Neoadjuvant Therapy of Microsatellite Stable (MSS) Locally Advanced Low Rectal Adenocarcinoma: an Prospective, Single Arm Clinical Trial （SCRIPBOT Trial）

A Prospective Single-Arm Study of Short-Course Radiotherapy Followed by PD-1 Monoclonal Antibody, Bevacizumab, Oxaliplatin, and Trifluridine/Tipiracil for Total Neoadjuvant Therapy in MSS Locally Advanced Low Rectal Cancer. This is a Non-Randomized, Single Group Assignment, Open Label, Phase: Phase II study. The Primary Objective is to assess the organ preservation rate (clinical complete response, cCR) after total neoadjuvant therapy. Secondary Objectives are Tumor regression grade (TRG), 3-year overall survival (OS) and disease-free survival (DFS), and Safety and quality of life (QoL). In this study, the investigators will perform the multi-dimensional omics study to explore the tumors microenvironments, explore the characteristics of the treatment benefit population, and try to construct an efficacy prediction model to screen the treatment benefit population early and implement precise treatment.

开始日期2025-04-01

申办/合作机构

Sir Run Run Shaw Hospital

NCT06869174

/ Not yet recruiting临床2期IIT

A Phase II Clinical Trial to Evaluate the Efficacy and Safety of Pucotenlimab in Combination with MRG002 in Treating HER2-positive Cancer of Unknown Primary

This study is a single-arm, open-label, multicenter Phase II clinical trial designed to observe and evaluate the efficacy and safety of Pucotenlimab in combination with MRG002 in patients with HER2-positive (IHC 2+ or 3+) cancer of unknown primary.

开始日期2025-03-08

申办/合作机构

复旦大学

100 项与普特利单抗相关的临床结果

登录后查看更多信息

100 项与普特利单抗相关的转化医学

登录后查看更多信息

100 项与普特利单抗相关的专利（医药）

登录后查看更多信息

项与普特利单抗相关的文献（医药）

2025-01-01·Journal for ImmunoTherapy of Cancer

Intratumoral oncolytic virus OH2 injection in patients with locally advanced or metastatic sarcoma: a phase 1/2 trial

Article

作者: Liu, Jiayong ; Zhang, Lu ; Fan, Zhengfu ; Xue, Ruifeng ; Gao, Tian ; Bai, Chujie ; Huang, Jing ; Luo, Suxia ; Zhou, Lixin ; Han, Liang ; Li, Shu ; Wang, Xinyu ; Shi, Jianhua ; Liu, Binlei ; Ding, Sijuan ; Tan, Zhichao ; Fan, Qingxia ; Jia, Ling ; Wu, Yan

Background:

Intratumoral oncolytic herpes simplex virus 2-GM CSF (OH2) injection has shown safety and antitumor efficacy in patients with solid tumors. Here, we examined the safety and efficacy of OH2 as a single agent or in combination with HX008, an NMPA-approved PD-1 inhibitor, in locally advanced or metastatic sarcoma patients.

Methods:

This multicenter, phase 1/2 trial enrolled patients with injectable sarcoma lesions, who had failed at least 1 or more lines of standard treatment. Patients were treated with OH2 at three dose levels (106, 107and 108CCID50/mL) as single agent or in combination with a fixed dose of HX008. The primary endpoints were safety and tolerability in phase 1 and objective response rate determined by RECIST (V.1.1) criteria and immune-RECIST in phase 2.

Results:

Between October 20, 2020 and December 30, 2023, 26 patients were enrolled. Seven patients were treated with single-agent OH2 and 19 with HX008 and OH2 combination. No dose-limiting toxicities were observed during the dose escalation. We documented four partial or complete responses in injected lesions, and one partial response in non-injected lesions, which were all from the combination group. Hence, the overall response rate was 0% and 16.7% in the single agent and combination groups, respectively. The duration of response was 3.9–6.5 months. The most frequent treatment-related adverse events (TRAEs) were fever (n=9). Grade 3 or 4 TRAEs were reported in four patients (15.4%). A clear increase in CD8+cell density in the tumor microenvironment was observed in the patients’ post-treatment specimens compared with baseline.

Conclusions:

Intratumoral injection of oncolytic virus OH2 is well tolerable in patients with sarcoma. Further investigation of OH2 with HX008 in select sarcoma subtypes is warranted.

2024-10-23·Zhonghua zhong liu za zhi [Chinese journal of oncology]

[Clinical predictive value of PD-1/PD-L1-induced electrocardiogram changes for cardiotoxicity].

Article

作者: Xue, N ; Li, X J ; Wu, D W ; Peng, L L

Objective: To observe the electrocardiogram (ECG) changes of programmed death receptor 1 (PD-1)/programmed death receptor-ligand 1 (PD-L1) immune checkpoint inhibitors before and after immunotherapy of patients during clinical antitumor process, and to explore the occurrence and influencing factors of cardiotoxicity of immune checkpoint inhibitors. Methods: A total of 93 patients with locally advanced or metastatic solid tumors confirmed by pathological diagnosis in Cancer Hospital of Chinese Academy of Medical Sciences from October 1, 2019 to September 30, 2020 were selected and treated with PD-1/PD-L1 inhibitor monotherapy. Groups were divided according to immunotherapy regimen: Group A (drug code: 609A), 16 patients were given 1 mg/kg of the drug for 21 days; Group B (drug code: HX008), 23 patients were treated with 200mg for 21 days; Group C (drug code: GB226), 28 patients were treated with 3mg/kg for 14 days; Group D (drug code: LP002), 26 patients were treated with 900mg for 14 days. The patients were monitored and followed up for 10 cycles. The ECG results of each group were recorded, and the correlation between ECG abnormality and cardiotoxicity was analyzed. Results: A total of 75 patients showed abnormal ECG that met the diagnostic criteria. There was no significant difference in abnormal ECG rate after immunotherapy in group A (P＞0.05), while the incidence of adverse cardiac events increased after immunotherapy in group B (P＜0.05), and the abnormal ECG rate increased significantly after chemotherapy in group C and group D. There was statistical difference before and after immunotherapy (P＜0.001). The number of abnormal cases in group A (8 cases, 50.0%, 8/16) was significantly lower than that of group B (20 cases, 87.0%, 20/23). The number of abnormal cases in group C and group D was 24 (85.7%) and 23 (88.4%), respectively, without statistical difference (P＞0.05), but their abnormal rates of ECG were higher than that in group A. The incidence of electrical adverse events in immunotherapy center of patients with underlying diseases was 1.93 times higher than that of patients without underlying diseases. The incidence of central electrical adverse events during immunotherapy in group B, C and D was 6.667, 6.000 and 7.667 times higher than that in group A, respectively. Conclusions: The high sensitivity of early ECG changes induced by immune checkpoint inhibitors enables early prediction of related cardiotoxicity. The presence or absence of comorbid underlying disease and drug dosage are correlated with the occurrence of adverse cardiac events, and these early changes provide a evidence for clinical treatment and prevention.

2023-12-01·Cell reports. Medicine

Pucotenlimab in patients with advanced mismatch repair-deficient or microsatellite instability-high solid tumors: A multicenter phase 2 study

Article

作者: Yin, Xianli ; Yu, Junyan ; Liang, Xinjun ; Li, Shengmian ; Liu, Zhihui ; Wang, Ke ; Zeng, Shan ; Liu, Yunpeng ; Dou, Yiwei ; Luo, Suxia ; Fan, Qingxia ; Wang, Fen ; Li, Enxiao ; Zhuang, Zhixiang ; Zhang, Shu ; Liu, Qian ; Zhang, Jingdong ; Huang, Jing ; Xu, Nong ; Kou, Xiaoge ; Zhu, Xiaodong ; Wang, Hui ; Song, Yan ; Bai, Yuxian ; Ma, Taiyang ; Shu, Yongqian ; Zhang, Bo ; Zhong, Haijun ; He, Yifu

We report a multicenter, phase 2 study evaluating the efficacy of pucotenlimab, an anti-PD-1 antibody, in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) tumors, and potential biomarkers for response. Overall, 100 patients with previously treated, advanced solid tumors centrally confirmed as dMMR or MSI-H received pucotenlimab at 200 mg every 3 weeks. The most common cancer type is colorectal cancer (n = 71). With a median follow-up of 22.5 months, the objective response rate is 49.0% (95% confidence interval 38.86%-59.20%) as assessed by the independent review committee, while the median progression-free survival and overall survival have not been reached. Grade ≥3 treatment-related adverse events were observed in 18 patients. For the biomarker analysis, responders are enriched in patients with mutations in the KMT2D gene. Pucotenlimab is an effective treatment option for previously treated advanced dMMR/MSI-H solid tumors, and the predictive value of KMT2D mutation warrants further research. This study is registered with ClinicalTrials.gov: NCT03704246.

125

项与普特利单抗相关的新闻（医药）

2025-03-04

·CPHI制药在线

乐普生物ADC新药MRG003上市被否？官方公告：主动撤回！

关注并星标CPHI制药在线 2025年3月3日，中国国家药品监督管理局（NMPA）官网发布消息，乐普生物的EGFR抗体偶联药物（ADC）维贝柯妥塔单抗（MRG003）收到药品通知件。根据惯例，药品通知件的出现通常意味着上市申请未获批准或企业主动撤回。随后，乐普生物在公告中明确表示，此次事件并非被拒，而是出于对药物研发的严谨态度和对监管要求的尊重，主动撤回了前次的上市申请（NDA），以补充相关资料并完善申报文件。图源 NMPA官网维贝柯妥塔单抗（MRG003）是乐普生物自主研发的靶向EGFR的ADC药物。EGFR（表皮生长因子受体）是一种跨膜蛋白，在细胞生长、发育和分化过程中发挥重要作用。然而，EGFR的过度表达及其与特异性配体的结合会导致EGFR异常激活，进而调控多条信号转导通路，抑制肿瘤细胞凋亡，促进细胞增殖、迁移，并通过介导VEGF表达促进肿瘤血管新生。因此，EGFR成为癌症治疗的重要靶点。 MRG003由EGFR靶向单抗与强效的微管抑制剂MMAE分子通过vc链接子偶联而成。它能够以高亲和力特异性地结合肿瘤细胞表面的EGFR，通过内吞进入肿瘤细胞后释放强效的有效载荷，从而导致肿瘤细胞死亡。这一独特的药物机制使得MRG003在肿瘤治疗中展现出巨大的潜力。乐普生物对MRG003的研发投入了大量的人力、物力和财力，从药物的靶点选择、分子设计、临床前研究到临床试验，每一个环节都经过了严格的科学验证和监管审批。特别是在临床试验阶段，乐普生物在国内外进行了多项临床试验，以评估MRG003的安全性、有效性和耐受性。在IIa期临床试验中，MRG003主要针对复发/转移性鼻咽癌（NPC）患者，入组了61例既往经至少二线系统化疗和PD-1/PD-L1抑制剂治疗失败的患者。截至2023年3月15日，对57位患者进行了疗效评估，结果显示，整体客观缓解率（ORR）为47.4%，疾病控制率（DCR）为79.0%。其中，2.0mg/kg剂量组的ORR为39.3%，DCR为71.4%；而2.3mg/kg剂量组的ORR和DCR分别高达55.2%和86.2%。这些数据表明，MRG003在复发/转移性鼻咽癌患者中具有显著的疗效。除了单药治疗外，乐普生物还探索了MRG003与PD-1抑制剂普特利单抗联用治疗实体瘤的方案。在一项入组33例患者的临床试验中，普特利单抗联合MRG003的ORR达到了63.0%，DCR为88.9%。特别是在二线临床部分，针对经PD-1+化疗一线治疗后进展的EGFR阳性鼻咽癌患者，ORR高达77.8%，DCR为100%。这些数据进一步证明了MRG003与免疫治疗药物联合使用的潜力。不过，乐普生物主动撤回MRG003的上市申请，背后原因可能涉及多个方面。首先，NMPA在审批新药时，会对临床试验数据的完整性和充分性进行严格审查。如果数据存在缺失、不一致，或无法充分证明药物的有效性和安全性，申请就可能被拒绝。MRG003虽然在IIa期临床试验中表现不错，但可能还需要更多数据来支持其上市申请。例如，临床试验的样本量相对较小，可能无法全面反映药物在更广泛患者群体中的疗效和安全性。此外，对于不同剂量组的疗效差异，也需要进一步的研究来确定最佳剂量和治疗方案。其次，药物的安全性和耐受性也是关键。在临床试验中，MRG003的治疗相关不良事件（TRAEs）主要包括皮疹、瘙痒、贫血和脱发等，大多数为1级或2级，且未出现与治疗直接相关的死亡事件。但严重不良事件（SAE）的发生率达到了11.5%，且有3名患者因不良事件退出治疗。尽管总体不良反应在可接受范围内，但为了取得业内外认可，取得患者信任，取得上市的十足把握，其安全性仍需进一步评估。再者，同类药物的竞争压力可能使得乐普对于MRG003有着更加严格的要求，已期后续能够在市场中赢得一席之地。EGFR靶点作为肿瘤治疗的重要靶点，吸引了众多制药企业的关注，国内外已有多款针对EGFR靶点的药物上市或处于临床试验阶段。例如，西妥昔单抗（Cetuximab）和奈妥木单抗（Necitumumab）是已获批的EGFR单克隆抗体，广泛用于肺癌等癌症的治疗。此外，贝达药业的MCLA-129和百济神州的BG-T187分别是靶向EGFR和c-MET的双特异性抗体和三特异性抗体，目前处于临床试验阶段。这些药物不仅在疗效和安全性上各有优势，还通过联合疗法或双靶点设计克服了单靶点药物的耐药性问题。这意味着MRG003需要展现出足够的竞争力，才能在激烈的市场竞争中脱颖而出。最后，政策监管环境的变化也可能使乐普对MRG003的上市申请做出了调整。近年来，中国药品监管政策发生了显著变化，药品审评审批制度的改革和国际化进程的加速，使得NMPA对新药上市申请的审批标准不断提高。例如，中国优化了临床试验要求，允许境外已上市但境内未上市的罕见病药品结合境内外数据减免境内临床试验。同时，药品注册检验用量大幅减少，注册核查启动方式也更加灵活。此外，中国还鼓励高水平医疗机构自行研制罕见病诊断试剂，并探索特定医疗机构先行进口临床急需的未注册药品。这些改革措施虽然加快了新药的上市速度，但也提高了对药物临床数据完整性和质量的要求。图源：乐普生物公告乐普生物公告称，此次撤回不会对MRG003的注册进程造成重大不利影响。公司已就申报材料进行补充并制备完成eCTD申报文件，已于3月4日重新提交MRG003的NDA，并将尽最大努力与监管机构合作完成后续审评程序，以获得NDA的上市批准。乐普生物的这一应对策略体现了其对药物研发的严谨态度和对监管要求的尊重。通过主动撤回并补充资料，公司能够更好地完善申报材料，提高其上市申请的成功率。同时，这也表明乐普生物在面对挑战时，能够迅速调整策略，以确保药物研发的科学性和合规性。参考来源： [1]NMPA官网 [2]Is ADC a rising star in solid tumor?An umbrella review of antibody-drug conjugates in solid tumors.BMC Cancer.2025. [3]EGFR-targeting RNase A-cetuximab antibody-drug conjugate.Scientific Reports.2025. 智药研习社近期会议预告扫码领取CPHI & PMEC China 2025展会门票来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com ▼更多制药资讯，请关注CPHI制药在线▼ 点击阅读原文，进入智药研习社~

临床结果抗体药物偶联物

2025-02-15

·药渡Daily

IBI363，而你又是哪里的火种？

关键提要：信达2024年收入超82亿元，同比增长>40%；在其2027年的200亿元目标中，GLP-1和PD-1将会占据半壁江山，作为信迪利单抗的接力者，PD-1/IL-2α-bias双抗IBI363现已在多种冷肿瘤，免疫不佳人群中获得积极进展 IBI363目前重点布局适应症包括：NSCLC，黑色素瘤，结直肠癌 2025年，是PD-1信迪利单抗获批上市的第7个年头。在这期间，有过开始的狂热追捧，也有后期的分道扬镳，而至今日，国内已有逾20款PD-(L)1产品，亦可见到齐鲁、百奥泰等的帕博利珠单抗类似药进入III期阶段。在滚烫的红海中求变的策略有很多。以扩增信迪利单抗适应症为基础，衍生出两个交叉分支： 1）IO+ADC。过去5年，信达大笔投资ADC，包括自研平台、多荷载ADC开发。今年1月，尚处于临床早期的DLL3 ADC IBI3009与罗氏达成首付款8千万美元的交易，即是ADC管线潜力的印证之一； 2）PD-(L)1的迭代。在横向探索其他免疫抑制剂企图复制前者辉煌的年间，以康方与普米斯为代表的PD-(L)1xVEGF bsAb无疑带来了新的思路启示，对于信达，这颗火种来自IBI363。 IBI363是信达开发的独创性的α偏向及减弱β、γ的结合的PD-1/IL-2α-bias双特异性抗体融合蛋白。在多种场合中，信达都有表示：这款药物可能会颠覆肿瘤免疫治疗领域。 IL-2是一个调控免疫细胞杀伤作用的重要细胞因子，主要由T细胞产生。它既可以通过高亲和受体αβγ三聚体诱导激活CD4+ Treg细胞，维持机体免疫抑制，又可以通过中亲和受体βγ二聚体刺激CD8+T和NK细胞，维持机体抗肿瘤作用。传统的IL-2作为药物分子时，有明显的缺点：1）半衰期短，很难达到持续的治疗水平，需要频繁静脉给药；2）信号通路复杂，免疫抑制会削弱药效；3）高剂量IL-2有效，但毒性作用显著，限制其广泛应用。海外曾重点开发非α偏向型IL-2，以提高对杀伤性T细胞的激活，不幸的是，Nektar和赛诺菲先后都折戟与于此。 Nektar的NKTR214是最早的一款非α偏向型IL-2。此前在2018年，Nektar曾与BMS达成一笔合作交易，首付高达18.5亿美元。但在2022年3月，公司宣告这款药物联合纳武利尤单抗1L治疗黑色素瘤在初步分析中并未达到主要终点；随后4月，这对联用组合在肾细胞癌和膀胱癌中也没有达到很好的疗效水平，由此两方终止合作，NKTR214正式退幕。赛诺菲也有类似的遭遇。2019年，其以25亿美元收购Synthorx，获得THOR-707，然而这款非α偏向型IL-2药物在临床试验中也未获得积极的疗效。在2022年10月份，赛诺菲正式宣布放弃这款药物的开发。这几乎明示一个事实，既往对于IL-2工程化改造的思路是有问题的，比如是否过度强调了α链对抗肿瘤的负面影响，而低估了其在肿瘤特异性T细胞上的短暂上调对抗肿瘤作用的影响。从这个角度来说，信达的α偏向改造，是冒险但又在情理之中。除了对IL-2的工程化改造以外，融合蛋白的形式也有助于提升IL-2的半衰期，从而拓展该类药物的治疗窗口；通过PD-1的特异性牵引，可以选择性刺激和扩增肿瘤内同时表达PD-1和CD25的T细胞，从而发挥抗肿瘤作用。尽管如此，IBI363所面临的市场竞争环境仍然非常激烈，无论是间接的来自其他类似功能bsAb，联合疗法等，还是来自已获批的大批PD-(L)1产品的直接竞争，它都需要找到自己的切入点——比如弥补治疗线中的空缺，或具有更好的安全性，疗效，依从性或价格优势？在2024年ESMO大会上，信达展示了更多关于IBI363的多瘤种数据。在这项Ia/Ib期研究中，共纳入了347例晚期实体瘤患者，包括100例NSCLC，89例黑色素瘤，102例CRC及56例其他肿瘤患者。在他们中，绝大多数都是既往接受过≥2L系统治疗，且在除了CRC以外的245例受试者中，有84.1%患者入组前接受过IO治疗。整体来说，在≥0.1mg/kg剂量范围内，先前免疫疗效不佳的200例患者中，ORR达到了17.6%；而在3mg/kg剂量组中，接受评估的15例患者的响应率达到了46.7%，DCR达到17.6%。有两个亮点值得关注，一是在剂量探索阶段，整体取得近18%的ORR，与传统的PD-1药物开发时获得的缓解率类似，且IBI363还是在IO经治的患者中；二是IBI363的剂量爬坡能到3mg/kg Q3W，与当下PD-1的用药一致，且安全性可控。不同瘤种中的积极数据，再次交叉验证了IBI363的安全性和有效性。先来说黑色素瘤。在上述研究中，既往接受过免疫治疗的37例患者经过1mg/kg IBI363治疗后，ORR为29.7%，DCR为73.0%；8例未经过免疫治疗的黏膜型黑色素瘤患者，总体ORR达到75%，DCR为100%。此外，信达也开展了一项评估IBI363对2L+晚期黑色素瘤患者的安全性和有效性的II期研究，其中一个队列包括了IO初治患者。一项分析综合了上述共计40例未经IO治疗的黑色素瘤患者，在可评估疗效的31例患者中，总体ORR达到了67.7%，DCR为87.1%。目前已有多款免疫抑制剂获批黑色素瘤适应症。以帕博利珠单抗为例，其在2018年7月在国内获批上市，用于2L治疗。在注册性研究中，帕博利珠单的ORR为16.7%，肢端和黏膜亚型则分别为15.8%和13.3%。而后上市的特瑞普利单抗，普特利单抗在2L的表现也相差无几，ORR为17.3%和20%。令人鼓舞的数据。很快，今年1月下旬，信达在CDE药物临床试验登记与信息公示平台上，登记了一项在未经治的晚期或转移性黏膜型及肢端型黑色素瘤患者中IBI363头对头对比帕博利珠单抗的II期研究，目标入组180人，IBI363的给药剂量为1mg/kg。如果该项试验结果积极，那么它将会成为关键性注册研究，支持IBI363在该适应症的国内上市。同时也为后续交易埋下伏笔，因为西方的黑色素瘤发病率更高。在今年的ASCO大会上，也能看到IBI363在NSCLC和结直肠癌的II期数据读出。这是IBI363押注的另外两大适应症，也是当下信达的股价所未反映出的潜力增幅。关于NSCLC，在去年WCLC大会上，信达公布了Ia/Ib期研究中的亚组更新数据，截至去年8月2日，共有134例患者接受了IBI363不同剂量治疗，其中95.5%比例的患者既往IO治疗后进展。在125例可评估患者中，总体ORR达到20.8%，DCR为74.4%。值得一提的是在肺鳞癌患者中的表现，在3mg/kg组中，经过短暂的12月随访，ORR能达到50%。另外在PD-L1低表达人群中，IBI363也达到了>30%的ORR。先前，康方的AK112在初治NSCLC患者中头对头对比帕博利珠单抗的III期研究中，表现出优越的PFS优势，在sq亚组中，PFS HR甚至达到了0.48，且安全性并无显著性差距。这使得人们将AK112视为当下肺鳞癌的初治标准疗法的有力冲击者之一。 IBI363寻找到的位置是IO失败的sqNSCLC。根据PoC及监管机构的讨论结果，可能会开展相关的III期研究。此外，关于1L NSCLC的 1b/2期试验也正在计划中。而从上我们也可以看到，对于无驱动基因改变的NSCLC, 双抗取代单抗，似乎成为不可避免的趋势。在一波波的冲击之下，只待谁会先撕开防线的裂口。在结直肠癌，IBI363也取得了进展。免疫疗法在晚期结直肠癌的的版图拓展有限，仅推荐在MSI-H/dMMR患者中可使用，具有特殊性。去年ESMO大会上，信达公布了IBI363+Beva在经治的非MSI-H/dMMR结直肠癌中患者的数据，在这35位患者中，54.3%存在肝转移，62.9%既往接受了≥3种系统治疗，可见整体的患者基线情况较差。在这种情况下，在32例可评估患者中ORR为18.8%，DCR为65.6%；17.1%患者发生≥3级TRAE。信达正在计划IBI363在3L的II期研究和1L的Ph1b研究。而在该领域，去年也有其他的IO利好消息。三药方案西达本胺+信迪利单抗+Beva在3L+治疗时，ORR达44.0%，mPFS达7.3个月，被视为MSS/pMMR晚期结直肠癌的极具前景的治疗选择。在IO经治，冷肿瘤中获得的疗效，也极大的膨胀了信达对于IBI363的未来预期。所以接下来的问题是：IBI363能否再现诸如PD-(L)1xVEGF的巨额交易？从信达方，对此表示一直持开放态度寻求潜在的BD机会。“在合作模式上，公司也非常灵活，包括授权、共同开发等多种方式，并会根据内部优先级列表和合作伙伴的具体需求来确定最终的合作模式。”其中管线，自然也包括IBI363。 IBI363潜在的合作方会来自哪里？很有可能将会从已有IO管线的海外Pharma中出现。以罗氏来说，其核心PD-L1阿替利珠单抗的US专利期为2028年；BMS的PD-1纳武利尤单抗的US专利期也为2028，CTLA-4伊匹木单抗则为2025年……寻找接力棒迫在眉睫。 2月6日，信达公布业绩，2024 年全年产品收入超82亿元人民币，同比增长超过 40%。在今年结束，其商业化产品矩阵数将会由现有的14增加≥18款产品，由此稳步迈向2027年国内市场收入达到200亿元的目标。在交流会答问时，信达曾表示，在这200亿元目标中，PD-1和GLP-1将会占比一半。玛仕度肽剑指司美格鲁肽，抢占减肥药的百亿市场；信迪利单抗2024年年销售38亿元，在增长减缓后，IBI363若要接力，还需走得更远一些。 1.Innovent Oncology Clinical Data Update in 2024 ASCO and ESMO Plenaryhttps://investor.innoventbio.com/media/1227/innovent_oncology_clinical_data_update_call_20240617.pdf 2.CDE药物临床试验登记与信息公示平台：CTR20250280 3.2024WCLC口头报告|全球首创PD-1/IL-2α-bias双特异性抗体融合蛋白IBI363治疗非小细胞肺癌临床I期数据发布

引进/卖出临床3期并购免疫疗法抗体药物偶联物

2025-01-22

·PRNewswire

Akeso Received Payment for the Development Collaboration on Tagitanlimab

HONG KONG, Jan. 22, 2025 /PRNewswire/ -- On January 22, 2025, Akeso Inc. (9926.HK) announced that it had received payment from Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. ("Sichuan Kelun") for their collaboration on the development of tagitanlimab, an innovative humanized monoclonal antibody targeting PD-L1, following its recent marketing approval by China's National Medical Products Administration. In 2014, Akeso signed a cooperation agreement with Sichuan Kelun for the development of tagitanlimab. Under the terms of the agreement, Akeso will receive royalties from the commercial sales of tagitanlimab in addition to the development payment. Tagitanlimab marks Akeso's second oncology product to yield commercial royalties, following pucotenlimab, a PD-1 monoclonal antibody developed in collaboration with Lepu Biopharma in 2016. Dr. Yu Xia, founder, chairwoman, president, and CEO of Akeso, said: "Congratulations to our partners. We are thrilled about continuously successful approval of our innovative products, and truly anticipate their outstanding commercialization performance. This achievement highlights Akeso's strong R&D capabilities and our commitment to innovation. Since its inception, Akeso has established multiple external collaborations, including ivonescimab with Summit Therapeutics, quavonlimab with Merck and pucotenlimab with Lepu Biopharma. These partnerships not only benefit patients but also deliver significant returns for both Akeso and our collaborators. Looking ahead, Akeso will continue to pursue a diversified strategy for new drug development, leveraging global resources to drive the high-quality commercialization of our independently developed innovative therapeutics." SOURCE Akeso, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

引进/卖出上市批准

100 项与普特利单抗相关的药物交易

登录后查看更多信息

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
黑色素瘤	中国	乐普生物科技股份有限公司	2022-09-20
MSI-H 实体瘤	中国	乐普生物科技股份有限公司	2022-07-19

未上市

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
错配修复缺陷或微卫星高度不稳定性结直肠癌	临床3期	中国	鼎康（武汉）生物医药有限公司	2023-02-28
错配修复缺陷或微卫星高度不稳定性结直肠癌	临床3期	中国	乐普生物科技股份有限公司	2023-02-28
栓塞	临床3期	中国	乐普生物科技股份有限公司	2023-02-03
栓塞	临床3期	中国	鼎康（武汉）生物医药有限公司	2023-02-03
转移性黑色素瘤	临床3期	中国	泰州翰中生物医药有限公司	2022-12-31
转移性结直肠癌	临床3期	中国	泰州翰中生物医药有限公司	2022-12-20
转移性微卫星稳定结直肠癌	临床3期	中国	泰州翰中生物医药有限公司	2022-12-20
胃食管交界处腺癌	临床3期	中国	乐普生物科技股份有限公司	2022-03-25
胃腺癌	临床3期	中国	乐普生物科技股份有限公司	2022-03-25
转移性非鳞状非小细胞肺癌	临床3期	中国	泰州翰中生物医药有限公司	2020-09-25

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


NCT05688605 (HX008/MRG003-C001, ESMO_ASIA2024) 人工标引	临床2期	鼻咽癌	30	Pucotenlimab (HX008) 3.0 mg/kg + EGFR-ADC (MRG003) 2.0 mg/kg	願糧構衊繭廠積壓築選(膚觸製膚壓憲艱築壓蓋) = 夢選網衊築窪簾淵鬱鏇艱觸夢鬱製範鏇獵製廠 (襯顧鏇選餘製積壓鹽鬱, 59.7 ~ 73.7) 更多	积极	2024-12-07
NCT04508803 (CHANGEABLE, ASCO2024) 人工标引	临床2期	转移性乳腺癌 BRCA2 Mutation (Germline)	37	Niraparib 200 mg qd + HX008 200 mg q3w	顧製襯網衊蓋簾獵製鏇(製夢蓋製築艱襯襯廠築) = 鏇範廠簾艱淵淵衊餘蓋繭蓋艱獵齋觸糧膚鹽蓋 (鏇構艱築齋鹹鏇網鹽鑰 ) 更多	积极	2024-05-24
NCT04508803 (CHANGEABLE, ASCO2024) 人工标引	临床2期	转移性乳腺癌 BRCA2 Mutation (Germline)	37	HX008+niraparib+pyrotinib	顧製襯網衊蓋簾獵製鏇(製夢蓋製築艱襯襯廠築) = 網衊窪構顧蓋醖鏇醖願繭蓋艱獵齋觸糧膚鹽蓋 (鏇構艱築齋鹹鏇網鹽鑰 ) 更多	积极	2024-05-24
NCT05688605 (Phase I/II study, ASCO2024) 人工标引	临床1/2期	EGFR 突变实体瘤 EGFR-positive	33	Pucotenlimab(HX008) + MRG003	製鹹襯窪構網鬱築選顧(襯襯鑰憲築蓋醖衊襯構) = 獵範選襯醖膚遞夢膚廠齋選範繭蓋廠憲膚餘窪 (醖夢鬱憲願鹹鏇觸淵簾 ) 更多	积极	2024-05-24
NCT04750083 (ESMO 12023 \| ESMO 22023) 人工标引	临床2期	非鳞状非小细胞肺癌一线 EGFR mutation \| ALK mutation	43	Pucotenlimab 200mg+pemetrexed+platinum	醖衊顧鏇憲齋築範鹹鬱(繭廠衊淵製鹽顧憲淵簾) = 製製膚網築顧遞鏇鏇鬱鹽憲憲齋壓願壓網構鏇 (網積築壓範蓋積壓廠構, 38.9 ~ 59.2) 更多	积极	2023-10-23
NCT05068453 (ASCO2023) 人工标引	临床1期	肝转移	10	Pucotenlimab+OH2	鑰觸襯衊艱願願觸膚壓(鹽願齋顧糧獵壓餘願衊) = 顧製窪鏇繭顧範觸簾觸構簾簾襯築築願鏇廠簾 (築鑰構範鹽選遞網顧夢 ) 更多	积极	2023-05-31
NCT04741165 (ASCO 12023 \| ASCO 22023) 人工标引	临床2期	晚期肝细胞癌一线	75	Bevacizumab+Pucotenlimab (C1)	鹹繭網艱網製築襯襯齋(鹹襯鏇糧蓋齋夢鏇壓觸) = 餘鑰齋築憲鹽齋醖製願鑰製餘範網廠鏇鑰鹽鏇 (鏇鏇齋襯鏇艱淵範繭艱 ) 更多	积极	2023-05-26
NCT04741165 (ASCO 12023 \| ASCO 22023) 人工标引	临床2期	晚期肝细胞癌一线	75	lenvatinib+Pucotenlimab (C2)	鹹繭網艱網製築襯襯齋(鹹襯鏇糧蓋齋夢鏇壓觸) = 衊鏇蓋顧網齋鏇遞選襯鑰製餘範網廠鏇鑰鹽鏇 (鏇鏇齋襯鏇艱淵範繭艱 ) 更多	积极	2023-05-26
NCT04749485 (Pubmed)	临床2期	局部晚期黑色素瘤	119	Pucotenlimab 3 mg/kg	醖構鹹鹹齋齋網製鏇膚(壓蓋選窪顧選鹹獵網鏇) = 窪繭獵鏇壓遞範顧壓齋鏇獵簾鏇製鹽鬱艱夢夢 (願鹹鬱艱鬱構願鏇築獵, 13.370% ~ 28.506%) 更多	-	2023-02-06
NCT03704246 (ASCO_GI2023) 人工标引	临床2期	MMRD实体瘤 \| MSI-H 实体瘤二线 MSI-H \| dMMR	100	200mg pucotenlimab	網簾壓遞願構鹹憲夢築(壓鹹餘製鏇觸繭積鹹鹽) = 蓋觸構積憲廠醖鏇願壓糧壓廠網蓋壓鏇鹽齋網 (衊選顧壓窪繭築蓋壓淵, 38.86 ~ 59.20) 更多	积极	2023-01-24
CTR20191353 (Pubmed) 人工标引	临床1期	三阴性乳腺癌一线 triple-negative	31	Gemcitabine+Cisplatin+Pucotenlimab	簾醖願餘積餘襯構蓋顧(積憲繭鹽遞顧範簾獵鹽) = neutropenia (74.1%), anemia (35.5%), thrombocytopenia (32.3%), hypocalcemia (9.7%), hypokalemia (9.7%), and alanine aminotransferase increased (6.5%). 艱鑰齋簾願齋遞憲築夢 (鹹糧衊襯獵窪構艱鏇範 )	积极	2022-08-02
NCT04486651 (HX008, CSCO2021)	临床2期	晚期胃癌 \| 胃食管交界处癌	58	HX008 + 伊立替康	醖製構鬱膚糧築簾構製(選鏇簾夢餘積遞餘衊構) = 34.5% 獵衊憲簾願選網鏇鏇淵 (壓壓構淵獵糧網餘鹽襯 ) 更多	积极	2021-09-25