更新于：2024-12-12
Cofetuzumab Pelidotin
更新于：2024-12-12
概要
基本信息
原研机构 |
非在研机构 |
最高研发阶段临床1期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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序列信息
Sequence Code 9988932H
来源: *****
Sequence Code 9988935L
来源: *****
关联
3
项与 Cofetuzumab Pelidotin 相关的临床试验A Phase 1b Efficacy and Safety Study of Cofetuzumab Pelidotin (ABBV-647, a PTK7-Targeting Antibody Drug Conjugate) in Subjects With PTK7-Expressing, Recurrent Non-Small Cell Lung Cancer
An Initial Safety Study of Gedatolisib Plus PTK7-ADC for Metastatic Triple-negative Breast Cancer
A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647020 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
100 项与 Cofetuzumab Pelidotin 相关的临床结果
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100 项与 Cofetuzumab Pelidotin 相关的转化医学
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100 项与 Cofetuzumab Pelidotin 相关的专利（医药）
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6
项与 Cofetuzumab Pelidotin 相关的文献（医药）2023-10-02Molecular cancer therapeutics
MTX-13, a Novel PTK7-Directed Antibody-Drug Conjugate with Widened Therapeutic Index Shows Sustained Tumor Regressions for a Broader Spectrum of PTK7-Positive Tumors.
Article
作者: Qian, Yu ; Hu, Wenhao ; Ma, Linjie ; Meng, Tao ; Meng, Xun ; Pu, Junyi ; Kong, Chao ; Zhao, Qianqian ; Weng, Weining
Protein tyrosine kinase 7 (PTK7) is a Wnt signaling pathway protein implicated in cancer development and metastasis. When using a potent microtubule inhibitor (Aur0101), PTK7-targeting antibody-drug conjugate (ADC), h6M24-vc0101 (PF-06647020/cofetuzumab pelidotin) is efficacious only in limited tumor types with low response rates in a phase I trial. To improve patient response and to expand responding tumor types, we designed MTX-13, a PTK7-targeting ADC consisting of a novel antibody (Ab13) conjugated to eight molecules of topoisomerase I inhibitor exatecan through T1000, a novel self-immolative moiety. MTX-13 exhibited PTK7-specific cell binding, efficient internalization, and exatecan release to cause cytotoxic activity through DNA damage and apoptosis induction, and a strong bystander killing. MTX-13 displayed potent antitumor activities on cell line-derived xenograft and patient-derived xenograft models from a wide range of solid tumors, significantly outperforming h6M24-vc0101. PTK7 was shown to be an actionable target in small cell lung cancer for which MTX-13 showed complete and durable responses. With a consistent overexpression of PTK7 in squamous cell carcinomas derived from diverse anatomic sites, strong potency of MTX-13 in this group of heterogenous tumors suggested a common treatment strategy. Finally, MTX-13 inhibited tumor growth and metastasis in an orthotopic colon cancer xenograft model. MTX-13 displayed a favorable pharmacokinetic and safety profile in monkeys with the highest non-severely toxic dose (HNSTD) of ≥30 mg/kg, significantly higher than 3-5 mg/kg of HNSTD for h6M24-vc0101. The higher therapeutic index of MTX-13 bodes well for its clinical translation with the potential to expand the responding patient population beyond that of current PTK7-targeting ADCs.
2022-08-02CLINICAL CANCER RESEARCH1区 · 医学
Initial Phase I Safety Study of Gedatolisib plus Cofetuzumab Pelidotin for Patients with Metastatic Triple-Negative Breast Cancer
1区 · 医学
Article
作者: Solzak, Jeffrey P. ; Badve, Sunil ; Radovich, Milan ; Ballinger, Tarah J. ; Miller, Kathy D. ; Schneider, Bryan P. ; Althouse, Sandra K. ; Bray, Steven M. ; Wang, Chao J. ; Hancock, Bradley A. ; Storniolo, Anna Maria V.
Abstract:
Purpose::
The PI3K pathway is dysregulated in the majority of triple-negative breast cancers (TNBC), yet single-agent inhibition of PI3K has been ineffective in TNBC. PI3K inhibition leads to an immediate compensatory upregulation of the Wnt pathway. Dual targeting of both pathways is highly synergistic against TNBC models in vitro and in vivo. We initiated a phase I clinical trial combining gedatolisib, a pan-class I isoform PI3K/mTOR inhibitor, and cofetuzumab pelidotin, an antibody–drug conjugate against the cell-surface PTK7 protein (Wnt pathway coreceptor) with an auristatin payload.
Patients and Methods::
Participants (pt) had metastatic TNBC or estrogen receptor (ER) low (ER and PgR < 5%, HER2-negative) breast cancer, and had received at least one prior chemotherapy for advanced disease. The primary objective was safety. Secondary endpoints included overall response rate (ORR), clinical benefit at 18 weeks (CB18), progression-free survival (PFS), and correlative analyses.
Results::
A total of 18 pts were enrolled in three dose cohorts: gedatolisib 110 mg weekly + cofetuzumab pelidotin 1.4 mg/kg every 3 weeks (n = 4), 180 mg + 1.4 mg/kg (n = 3), and 180 mg + 2.8 mg/kg (n = 11). Nausea, anorexia, fatigue, and mucositis were common but rarely reached ≥grade 3 severity. Myelosuppression was uncommon. ORR was 16.7% (3/18). An additional 3 pts had stable disease (of these 2 had stable disease for >18 weeks); CB18 was 27.8%. Median PFS was 2.0 months (95% confidence interval for PFS: 1.2–6.2). Pts with clinical benefit were enriched with genomic alterations in the PI3K and PTK7 pathways.
Conclusions::
The combination of gedatolisib + cofetuzumab pelidotin was well tolerated and demonstrated promising clinical activity. Further investigation of this drug combination in metastatic TNBC is warranted.
2022-07-01The AAPS journal
Joint Disposition Properties and Comprehensive Pharmacokinetic Characterization of Antibody–Drug Conjugates
Article
作者: Williams, Jason H ; Palani, Santhosh ; Yin, Donghua ; Meng, Xu ; Liao, Kai H
Abstract:
Antibody–drug conjugates (ADCs) comprise 3 distinct parts: a specific antibody carrier (mAb), a linker, and a cytotoxic payload. Typical pharmacokinetic (PK) characterization of ADCs remains fragmented using separate noncompartmental analyses (NCA) of individual analytes, offering little insight into the dynamic relationships among the ADC components, and the safety and efficacy implications. As a result, it is exceedingly difficult to compare ADCs in terms of favorable PK characteristics. Therefore, there is a need for characterizing ADCs using the joint disposition properties critical for understanding the fate of an ADC complex and clinical implications. In this communication, we describe 3 joint disposition metrics (JDMs) for integrated NCA of ADCs based on a combination of common analytes of ADC, payload, conjugated payload, and total mAb. These JDMs were derived, each in a simple form of a ratio between appropriate PK parameters of two analytes, from the presumed drug delivery scheme behind typical ADC designs, in terms of (1) linker stability, (2) therapeutic exposure ratio, and (3) effective drug-to-antibody ratio in vivo. The validity of the JDM-based PK characterization was examined against model-based analyses via their applications to 3 clinical candidates: PF-06650808, PF-06647020, and PF-06664178. For instance, the linker stability estimates for PF-06650808, PF-06647020, and PF-06664178 were 0.31, 0.14, and 0.096, respectively, from the JDM-based analyses vs. 0.23, 0.11, and 0.086 by the model-based approach. Additionally, the JDMs were estimated for a number of FDA-approved or otherwise well-documented ADCs, showing their utilities in comparing ADCs in terms of favorable PK characteristics.Graphical Abstract
49
项与 Cofetuzumab Pelidotin 相关的新闻（医药）2024-12-12
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100 项与 Cofetuzumab Pelidotin 相关的药物交易
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外链
| KEGG | Wiki | ATC | Drug Bank |
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| D11118 | Cofetuzumab Pelidotin | - | - |
研发状态
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 复发性非小细胞肺癌 | 临床1期 | 美国 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 美国 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 日本 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 日本 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 以色列 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 以色列 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 韩国 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 韩国 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 西班牙 | 2020-02-13 | |
| 复发性非小细胞肺癌 | 临床1期 | 西班牙 | 2020-02-13 |
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临床结果
临床结果
适应症
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临床1期 | 112 | 夢鹽艱窪選製鏇壓夢鑰(餘窪製獵製齋鹽壓窪繭) = Common treatment-related AEs were nausea, alopecia, fatigue, headache, neutropenia, and vomiting 餘餘醖憲衊鹹範餘醖鏇 (壓膚衊糧構築製膚齋壓 ) | 积极 | 2018-06-01 | |||
临床1期 | 112 | 蓋遞觸糧齋廠齋觸鬱鏇(築遞築鹹餘餘窪範憲構) = 鑰範願簾鏇衊鑰鬱願窪 鑰願餘構鏇願範鏇衊鏇 (遞餘衊餘廠繭鑰選鹽範 ) 更多 | - | 2018-06-01 |
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