重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）(Erfonrilimab) - 药物靶点：CTLA4 x PDL1_在研适应症：HER2阳性胃食管交界处癌，晚期胰腺导管腺癌，鳞状非小细胞肺癌_专利_临床

概要

基本信息

药物类型

双特异性抗体

别名

Recombinant Humanized PDL1/CTLA-4 Bispecific Domain Antibody Fc Fusion Protein、重组人源化PD-L1/CTLA4双特异性单域抗体Fc融合蛋白、KN 046

+ [1]

靶点

CTLA4 x PDL1

作用方式

抑制剂

作用机制

CTLA4抑制剂(细胞毒性T淋巴细胞相关抗原4抑制剂)、PDL1抑制剂(程序性死亡配体1抑制剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [3]

在研适应症

HER2阳性胃食管交界处癌晚期胰腺导管腺癌鳞状非小细胞肺癌+ [12]

非在研适应症

晚期食管鳞状细胞癌晚期胃癌晚期肝细胞癌+ [13]

原研机构

在研机构

+ [1]

非在研机构

苏州泽璟生物制药股份有限公司Alphamab Australia Co. Pty Ltd.浙江瑞臻医药有限公司

权益机构

浙江瑞臻医药有限公司

江苏康宁杰瑞生物制药有限公司

苏州康宁杰瑞生物科技有限公司

+ [3]

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)临床3期

特殊审评孤儿药 (美国)、特殊审批 (中国)

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结构/序列

Sequence Code 453187443H

来源: *****

关联

43

项与重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）相关的临床试验

ChiCTR2500109757

/ RecruitingN/AIIT

Clinical Study on Pathological Remission and Safety of JSKN003 Combined with KN046 New Adjuvant Therapy for muscle-invasive bladder cancer

开始日期2024-04-01

申办/合作机构-

NCT05832892

/ Unknown status临床1/2期IIT

A Phase Ib/II Clinical Trial to Evaluate the Efficacy and Safety of Surufatinib in Combination With KN046 and AG Regimen Chemotherapy for the First-Line Treatment of Unresectable Advanced Pancreatic Cancer

Advanced pancreatic cancer is a highly aggressive and fatal disease with an extremely low 5-year survival rate. Combined chemotherapy is the mainstay of treatment for patients with unresectable advanced pancreatic cancer, and the combination of nab-paclitaxel and gemcitabine (AG regimen) has been one of the most commonly used regimens for more than a decade. However, chemo-resistance often occurs within half a year and the efficacy remains unsatisfied with an overall survival of only 9
11 months.
Immune checkpoint inhibitors (ICIs) such as anti-PD-1/L1 antibody and anti-CTLA-4 antibody have demonstrated encouraging anti-tumor efficacy in multiple solid tumors including lung cancer, gastric cancer, and esophageal cancer, while obtained controversial results when combined with chemotherapy in pancreatic cancer. Recently, the immune-suppression tumor microenvironment (TME) of pancreatic cancer has been described in several pre-clinical studies, which may explain the resistance against ICIs and chemotherapy.
KN046 is a recombinant humanized PD-L1/CTLA-4 bispecific antibody with innovative designs include a proprietary CTLA-4 domain antibody with a significantly improved safety profile, a bispecific antibody fused with PD-L1 antibody targeting the TME with high PD-L1 expression. Recent clinical studies have shown promising anti-tumor activity of KN046 in pancreatic cancer.
Surufatinib, also known as HMPL-012 or Sulfatinib, is a small molecular tyrosine kinase inhibitor (TKI) targeting the Vascular Endothelial Growth Factor Receptor (VEGFR), Fibroblast Growth Factor Receptor (FGFR) and Colony Stimulating Factor-1 Receptor (CSF-1R), which has a dual mechanism of action of anti-angiogenesis and regulation of immune microenvironment. Previous studies have suggested synergic effect of surufatinib in combination with anti-PD-1 antibodies.
This phase Ib/II clinical trial is intended to investigate the activity and safety of the combination of surufatinib combined with KN046 and the AG regimen chemotherapy as first-line treatment in patients with unresectable locally advanced or metastatic pancreatic cancer.

开始日期2023-11-01

申办/合作机构

复旦大学附属中山医院

[+1]

NCT05985109

/ Recruiting临床2期IIT

A Phase II Multi-cohort Clinical Study Evaluating The Efficacy and Safety of KN046 in Combination With Regorafenib for Metastatic Microsatellite-Stable Colorectal Cancer: a Phase II Multi-cohort Study

The study is an interventional Phase II clinical trial aiming to optimize immunotherapy strategies for microsatellite-stable colorectal cancer. We will include three types of metastatic colorectal cancer patients: those without liver metastasis, or carrying BRAF V600E mutation, or unable to tolerate chemotherapy as their initial or second-line treatment. The participants will receive a combination treatment of regorafenib and KN046 which is a PD-L1/CTLA-4 bispecific antibody. Treatment efficacy and safety profile would be evaluated in this study.

开始日期2023-10-26

申办/合作机构

北京市肿瘤防治研究所

100 项与重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）相关的临床结果

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100 项与重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）相关的转化医学

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100 项与重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）相关的专利（医药）

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21

项与重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）相关的文献（医药）

2025-12-31·mAbs

Antibodies to watch in 2025

Review

作者: Kapoor, Vaishali ; Crescioli, Silvia ; Kaplon, Hélène ; Visweswaraiah, Jyothsna ; Reichert, Janice M. ; Wang, Lin

The commercial development of antibody therapeutics is a global enterprise involving thousands of biopharmaceutical firms and supporting service organizations. To date, their combined efforts have resulted in over 200 marketed antibody therapeutics and a pipeline of nearly 1,400 investigational product candidates that are undergoing evaluation in clinical studies as treatments for a wide variety of diseases. Here, we discuss key events in antibody therapeutics development that occurred during 2024 and forecast key events related to the late-stage clinical pipeline that may occur in 2025. In particular, we report on 21 antibody therapeutics granted a first approval in at least one country or region during 2024, including bispecific antibodies tarlatamab (IMDELLTRA®), zanidatamab (Ziihera®), zenocutuzumab (BIZENGRI®), odronextamab (Ordspono®), ivonescimab (®), and antibody-drug conjugate (ADC) sacituzumab tirumotecan (®). We also discuss 30 investigational antibody therapeutics for which marketing applications were undergoing review by at least one regulatory agency, as of our last update on December 9, 2024, including ADCs datopotamab deruxtecan, telisotuzumab vedotin, patritumab deruxtecan, trastuzumab botidotin, becotatug vedotin, and trastuzumab rezetecan. Of 178 antibody therapeutics we include in the late-stage pipeline, we summarize key data for 18 for which marketing applications may be submitted by the end of 2025, such as bi- or multispecific antibodies denecimig, sonelokimab, erfonrilimab, and anbenitamab. Key trends in the development and approval of antibody formats such as bispecifics and ADCs, as well as clinical-phase transition and global approval success rates for these antibody formats, are reported.

2025-06-13·CLINICAL CANCER RESEARCH

Safety and Efficacy of KN046 in Combination with KN026 in Patients with Advanced HER2-Positive Breast Cancer: A Phase II Trial

Article

作者: Liu, Jieqiong ; Wang, Xiangcai ; Wang, Xujuan ; Shen, Lin ; Ni, Mingli ; Yang, Hongwei ; Yang, Yaping ; Song, Chuangui ; Zhao, Rusen ; Xu, Ting ; Chen, Lei

Abstract:

Purpose::

In this study, we report the results from a phase II trial assessing the safety and efficacy of KN046 in combination with KN026 in patients with HER2-positive metastatic breast cancer, who had progressed after prior anti-HER2 combination therapies.

Patients and Methods::

Female patients with metastatic HER2-positive breast cancer, who were previously treated with at least one line of HER2-targeted combination therapy, were enrolled from multiple academic hospitals in China to receive KN046 (i.v. 5 mg/kg every 3 weeks) plus KN026 (i.v. 30 mg/kg every 3 weeks) until progression, unacceptable toxicities, or patient withdrawal. Efficacy was evaluated every 6 weeks per RECIST 1.1. The primary endpoint was objective response rate.

Results::

A total of 36 patients with the median age of 53 years were enrolled. Of these 36 patients, 30 (83.3%) received ≥3 lines of HER2-targeted combination therapies in the metastatic setting. Thirty-three patients were evaluable for overall response and all 36 for safety. The objective response rate was 47.2% (95% confidence interval, 30.4–64.5), with two patients achieving complete response. The median progression-free survival was 5.6 months (95% confidence interval, 4.1–13.8). Of the 36 patients, 34 (94.4%) experienced treatment-related adverse events (TRAE) of any grade, and 10 of 36 (27.8%) patients had experienced ≥grade 3 TRAEs. The most common TRAEs were infusion-related reaction (36.1%), rash (16.7%), alanine aminotransferase increased (13.9%), diarrhea (13.9%), and pruritus (13.9%). No treatment-related deaths were observed.

Conclusions::

The combination of KN046 and KN026, as a chemo-free regimen, demonstrated favorable clinical efficacy with comparative toxicities in pretreated patients with advanced HER2-positive breast cancer.

2024-12-31·mAbs

Antibodies to watch in 2024

Article

作者: Kaplon, Hélène ; Crescioli, Silvia ; Wang, Lin ; Reichert, Janice M. ; Visweswaraiah, Jyothsna ; Chenoweth, Alicia

The 'Antibodies to Watch' article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.

199

项与重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）相关的新闻（医药）

2025-10-22

·证券之星

康宁杰瑞制药-B（09966.HK）10月22日收盘跌2.47%，主力资金净流入232.42万港元

证券之星消息，截至2025年10月22日收盘，康宁杰瑞制药-B(09966.HK)报收于13.05港元，下跌2.47%，成交量307.4万股，成交额4039.37万港元。资金流向数据方面，10月22日康宁杰瑞制药-B主力资金净流入232.42万港元，超大单资金净流入390.26万港元，大单资金净流出157.84万港元，中单资金净流出245.52万港元，小单资金净流入234.05万港元。投行对该股的评级以推荐为主，近90天内共有1家投行给出推荐评级。平安证券股份有限公司最新一份研报给予康宁杰瑞制药-B推荐评级。康宁杰瑞生物制药是一家主要从事肿瘤生物制剂研发、制造及商业化的投资控股公司。该公司高度差异化的内部管线由处于不同研发阶段的ADCs、单克隆抗体及双特异性抗体肿瘤药物组成。该公司的候选药物包括KN046（PD-L1/CTLA-4双特异性抗体）, KN026（抗HER2双特异性抗体）, KN035（皮下注射PD-L1）, JSKN003（HER2双表位ADC）等，用于1L sq NSCLC、乳腺癌 2+HER L1、晚期实体瘤、HER2表达实体瘤等适应症。以上内容为证券之星据公开信息整理，由AI算法生成（网信算备310104345710301240019号），不构成投资建议。

抗体药物偶联物

2025-10-21

·证券之星

康宁杰瑞制药-B（09966.HK）：10月21日南向资金减持89.3万股

证券之星消息，10月21日南向资金减持89.3万股康宁杰瑞制药-B（09966.HK）。近5个交易日中，获南向资金减持的有5天，累计净减持118.6万股。近20个交易日中，获南向资金减持的有20天，累计净减持485.5万股。截至目前，南向资金持有康宁杰瑞制药-B（09966.HK）1.79亿股，占公司已发行普通股的18.36%。康宁杰瑞生物制药是一家主要从事肿瘤生物制剂研发、制造及商业化的投资控股公司。该公司高度差异化的内部管线由处于不同研发阶段的ADCs、单克隆抗体及双特异性抗体肿瘤药物组成。该公司的候选药物包括KN046（PD-L1/CTLA-4双特异性抗体）, KN026（抗HER2双特异性抗体）, KN035（皮下注射PD-L1）, JSKN003（HER2双表位ADC）等，用于1L sq NSCLC、乳腺癌 2+HER L1、晚期实体瘤、HER2表达实体瘤等适应症。以上内容为证券之星据公开信息整理，由AI算法生成（网信算备310104345710301240019号），不构成投资建议。

抗体药物偶联物

2025-10-21

·证券之星

康宁杰瑞制药-B（09966.HK）：10月21日南向资金减持89.3万股

证券之星消息，10月21日南向资金减持89.3万股康宁杰瑞制药-B（09966.HK）。近5个交易日中，获南向资金减持的有5天，累计净减持118.6万股。近20个交易日中，获南向资金减持的有20天，累计净减持485.5万股。截至目前，南向资金持有康宁杰瑞制药-B（09966.HK）1.79亿股，占公司已发行普通股的18.36%。康宁杰瑞生物制药是一家主要从事肿瘤生物制剂研发、制造及商业化的投资控股公司。该公司高度差异化的内部管线由处于不同研发阶段的ADCs、单克隆抗体及双特异性抗体肿瘤药物组成。该公司的候选药物包括KN046（PD-L1/CTLA-4双特异性抗体）, KN026（抗HER2双特异性抗体）, KN035（皮下注射PD-L1）, JSKN003（HER2双表位ADC）等，用于1L sq NSCLC、乳腺癌 2+HER L1、晚期实体瘤、HER2表达实体瘤等适应症。以上内容为证券之星据公开信息整理，由AI算法生成（网信算备310104345710301240019号），不构成投资建议。

抗体药物偶联物

100 项与重组人源化PDL1/CTLA-4双特异性单域抗体Fc融合蛋白（康宁杰瑞）相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
HER2阳性胃食管交界处癌	临床3期	中国	江苏康宁杰瑞生物制药有限公司	2022-10-27
晚期胰腺导管腺癌	临床3期	中国	江苏康宁杰瑞生物制药有限公司	2022-01-20
晚期非小细胞肺癌	临床3期	中国	江苏康宁杰瑞生物制药有限公司	2021-10-11
鳞状非小细胞肺癌	临床3期	中国	江苏康宁杰瑞生物制药有限公司	2020-09-14
转移性结直肠癌	临床2期	中国	北京市肿瘤防治研究所	2023-10-26
转移性微卫星稳定结直肠癌	临床2期	中国	北京市肿瘤防治研究所	2023-10-26
HER2阳性胆道肿瘤	临床2期	中国	北京市肿瘤防治研究所	2023-08-15
HER2阳性结直肠癌	临床2期	中国	北京市肿瘤防治研究所	2023-08-15
不能切除的胆道癌	临床2期	中国	北京市肿瘤防治研究所	2023-08-15
结肠癌肝转移	临床2期	中国	江苏康宁杰瑞生物制药有限公司	2023-04-27

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04542837 (Pubmed) 人工标引	临床2期	肝细胞癌	55	KN046 + Lenvatinib	鬱蓋選鏇簾構壓構餘窪(願淵鹹憲窪窪糧壓築壓) = 餘廠艱廠顧衊窪糧廠願襯糧簾網選憲簾醖鏇觸 (構鑰製齋獵積願鏇壓齋, 31.97 ~ 59.45) 更多	积极	2025-02-07
NCT05420220 (ESMO_IO2024) 人工标引	临床2期	晚期非小细胞肺癌	85	KN046 + Axitinib (Cohort A (previously untreated and PD-L1 TPS ≥1%))	醖鏇窪醖鑰廠願廠遞壓(艱壓範衊願築憲餘窪構) = 窪築餘醖蓋鏇築獵鑰顧鏇艱襯製廠窪築鏇醖廠 (繭衊網鑰繭鹽襯鏇簾網, 38.8 ~ 69.6) 更多	积极	2024-12-12
NCT05420220 (ESMO_IO2024) 人工标引	临床2期	晚期非小细胞肺癌	85	KN046 + Axitinib (Cohort A (previously untreated and PD-L1 TPS ≥50%))	醖鏇窪醖鑰廠願廠遞壓(艱壓範衊願築憲餘窪構) = 製齋襯顧鑰製鬱憲顧餘鏇艱襯製廠窪築鏇醖廠 (繭衊網鑰繭鹽襯鏇簾網, 38.4 ~ 88.2) 更多	积极	2024-12-12
NCT05149326 (KN046-303, Corporate Publications) 人工标引	临床3期	胰腺导管腺癌一线	-	KN046+白蛋白紫杉醇+吉西他滨	糧網廠鹹積願壓廠構餘(襯積夢選簾獵衊窪齋衊) = 未达到预设的统计学终点網積壓範遞鏇淵餘顧積 (膚範鬱製襯繭繭製鑰鏇 ) 未达到	不佳	2024-05-28
NCT05149326 (KN046-303, Corporate Publications) 人工标引	临床3期	胰腺导管腺癌一线	-	安慰剂+白蛋白紫杉醇+吉西他滨		不佳	2024-05-28
NCT04925947 (CTgov)	临床2期	胸腺癌	4	KN046	夢廠築觸淵窪獵遞願襯 = 製簾鹹鏇艱網淵襯鹹範醖鏇鹹鏇壓繭構鬱鑰築 (醖範鏇獵鏇憲選壓窪襯, 觸窪觸範製繭鹹觸淵夢 ~ 獵壓夢構淵繭簾糧顧蓋) 更多	-	2024-04-16
NCT04054531 (Cell Rep Med) 人工标引	临床2期	转移性非小细胞肺癌一线	-	KN046+chemotherapy	壓築範齋鹹壓簾築醖網(壓積積齋願鬱餘餘淵範) = 製觸壓淵構廠鬱顧糧遞廠築繭顧繭願鹹糧襯築 (蓋積鬱壓襯糧鑰壓膚鏇 ) 更多	积极	2024-03-19
NCT03872791 (Pubmed) 人工标引	临床2期	转移性三阴性乳腺癌一线 ER Negative \| PR Negative \| HER2 Negative	25	KN046+nab-paclitaxel	遞繭糧鬱淵積醖襯製繭(網憲餘壓鏇壓築遞齋衊) = 蓋積製廠淵醖廠鑰糧衊積選範鑰鑰廠築鹽觸醖 (衊範鬱遞範鹹淵遞範艱, 24.4 ~ 65.1) 更多	积极	2024-02-03
NCT03872791 (Pubmed) 人工标引	临床2期	转移性三阴性乳腺癌一线 ER Negative \| PR Negative \| HER2 Negative	25	KN046+nab-paclitaxel (PD-L1 positive)	蓋繭廠積淵遞鹽簾壓鹽(餘淵蓋構鑰選艱鑰淵憲) = 蓋鑰範廠夢鏇觸製淵繭糧醖鏇壓醖遞廠餘餘夢 (遞壓獵遞顧壓顧顧網遞 ) 更多	积极	2024-02-03
NCT03838848 (ESMO 12023 \| ESMO 22023) 人工标引	临床2期	转移性非小细胞肺癌 EGFR L858R \| EGFR Exon 19 Deletion	26	KN046 5 mg/kg + Pemetrexed 500 mg/m2+carboplatin AUC5	壓壓鹹齋醖網廠壓獵顧(簾醖獵衊鹹簾網觸淵願) = 鏇廠憲獵繭壓築鹽顧顧鬱鏇蓋衊選衊齋淵憲糧 (窪憲艱鑰鏇繭遞構膚鑰, 11.6 ~ 47.8) 更多	积极	2023-10-23
NCT05420220 (ESMO 12023 \| ESMO 22023) 人工标引	临床2期	非小细胞肺癌一线 PD-L1 expression	22	KN046 5mg/kg + Axitinib 5mg	襯選鹹衊齋鏇夢繭遞餘(廠壓顧顧淵憲鑰餘獵範) = 廠夢醖蓋簾餘積鹽構簾糧範艱鏇遞鹽範艱夢觸 (衊廠齋衊鹹遞壓餘餘鹹 ) 更多	积极	2023-10-23
NCT03733951 \| NCT03838848 (KN046-201, ESMO 12023 \| ESMO 22023) 人工标引	临床1/2期	转移性非小细胞肺癌	31	KN046	鹹憲齋膚簾簾願鏇簾繭(獵顧遞鏇齋餘糧襯鬱觸) = 願襯襯獵繭願鹽鹽醖築鑰簾積蓋齋築構壓網範 (顧願齋願窪鹹淵膚齋衊, 0.1 ~ 16.7) 更多	积极	2023-10-23
NCT04469725 (ESMO 12023 \| ESMO 22023) 人工标引	临床2期	胸腺癌 PD-L1 Expression	46	KN046	獵鏇夢蓋繭繭淵淵鹹繭(襯窪製憲觸鹹廠鏇鏇構) = 餘廠襯顧簾鹽艱艱糧壓鹹築顧鹹繭窪衊鹽繭蓋 (夢憲範蓋壓顧觸襯遞膚, 6.8 ~ 30.7) 更多	积极	2023-10-21
NCT04469725 (ESMO 12023 \| ESMO 22023) 人工标引	临床2期	胸腺癌 PD-L1 Expression	46	KN046 (PD-L1-positive)	獵鏇夢蓋繭繭淵淵鹹繭(襯窪製憲觸鹹廠鏇鏇構) = 鹹遞鹽簾鹹艱醖觸願積鹹築顧鹹繭窪衊鹽繭蓋 (夢憲範蓋壓顧觸襯遞膚 ) 更多	积极	2023-10-21