LY-3022855(LY-3022855) - 药物靶点：CSF-1R_在研适应症：胰腺导管腺癌_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-CSF-1R-monoclonal-antibody-ImClone

+ [1]

靶点

CSF-1R

作用方式

拮抗剂

作用机制

CSF-1R拮抗剂(集落刺激因子1受体拮抗剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病

在研适应症

胰腺导管腺癌

非在研适应症

晚期恶性实体瘤局部晚期黑色素瘤非小细胞肺癌

原研机构

Eli Lilly & Co.

在研机构

Eli Lilly & Co.

Merck Sharp & Dohme Corp.

非在研机构-

最高研发阶段早期临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 177912VH

Sequence Code 66219CDR3-L

Sequence Code 177917VL

Sequence Code 2266CDR2-L

Sequence Code 177898CDR1-L

Sequence Code 2173CDR2-H

Sequence Code 2657CDR1-H

Sequence Code 177893CDR3-H

关联

5

项与 LY-3022855 相关的临床试验

NCT03153410

/ Completed早期临床1期IIT

A Pilot Study of a GVAX Pancreas Vaccine (With Cyclophosphamide) in Combination With a PD-1 Blockade Antibody (Pembrolizumab) and a Macrophage Targeting Agent (CSF1R Inhibitor) for the Treatment of Patients With Borderline Resectable Adenocarcinoma of the Pancreas

The purpose of this study is to evaluate whether combining cyclophosphamide (CY), pembrolizumab, GVAX and IMC-CS4 is effective and safe in patients with borderline resectable pancreatic cancer.

开始日期2018-09-27

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT03101254

/ Completed临床1/2期IIT

A Phase I/II Study of LY3022855 With BRAF/MEK Inhibition in Patients With Melanoma

This research study is studying a combination of targeted therapies as a possible treatment for advanced melanoma that was found to have a BRAF V600E or BRAF V600K genetic mutation
The interventions involved in this study are:
* LY3022855
* Vemurafenib
* Cobimetinib

开始日期2017-06-06

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+1]

NCT02718911

/ Completed临床1期

A Phase 1a/1b Trial Investigating the CSF-1R Inhibitor LY3022855 in Combination With Durvalumab (MEDI4736) or Tremelimumab in Patients With Advanced Solid Tumors

The main purpose of this study is to evaluate the safety of the colony-stimulating factor 1 receptor (CSF-1R) inhibitor LY3022855 in combination with durvalumab or tremelimumab in participants with advanced solid tumors.

开始日期2016-06-16

申办/合作机构

Eli Lilly & Co.

[+1]

100 项与 LY-3022855 相关的临床结果

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100 项与 LY-3022855 相关的转化医学

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100 项与 LY-3022855 相关的专利（医药）

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4

项与 LY-3022855 相关的文献（医药）

2023-08-01·Investigational new drugs

A phase I/II study of LY3022855 with BRAF/MEK inhibition in patients with Melanoma.

Article

作者: Ott, Patrick A ; Haq, Rizwan ; Buchbinder, Elizabeth I ; Giobbie-Hurder, Anita

BRAF/MEK targeted therapies and immune checkpoint inhibition have dramatically improved disease control and survival of patients with advanced melanoma. However, most patients do not have durable benefit from either of these therapies. BRAF targeted therapy often has a limited duration of efficacy due to the development of resistance. Pre-clinical data suggest that one possible way to overcome resistance to BRAF/MEK targeted therapy may be the addition of CSF1R inhibition. In this phase I/II study we evaluated the safety and efficacy of LY3022855, an anti-colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody in combination with the BRAF inhibitor vemurafenib and the MEK inhibitor cobimetinib in patients with BRAF V600^E/K mutant metastatic melanoma. The trial was terminated early due to discontinuation of the development program for LY3022855 by the sponsor. Between August 2017 and May 2018 five pts were enrolled. Three patients experienced grade 3 events that were deemed possibly related to LY3022855. There were no grade 4 or grade 5 events related to LY3022855. One of the 5 patients had a complete response (CR), whereas the other 4 had progressive disease (PD). Median progression free survival was 3.9 months (90% CI: 1.9-37.2 mos). CSF1R inhibition with LY3022855 in combination with BRAF/MEK inhibition with vemurafenib and cobimetinib was difficult to tolerate in a small melanoma population. One response was observed in this small sample of patients suggesting this combination might be worthy of further exploration.

2021-10-01·Investigational New Drugs3区 · 医学

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

3区 · 医学

Article

作者: Cohen, Jonathan E ; Bauer, Todd M ; Falchook, Gerald S ; Wang, Judy S ; Obermannova, Radka ; Chapman, Sonya ; Sabari, Joshua ; Peeters, Marc ; Zhang, Wei ; Peterson, Daniel A ; Rottey, Sylvie ; Dirix, Luc Y ; Calderon, Boris ; Perets, Ruth ; Frommer, Ronnie Shapira ; Carvajal, Richard D

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W. ClinicalTrials.gov ID: NCT02718911 (Registration Date: May 3, 2011).

2021-08-01·Investigational New Drugs3区 · 医学

LY3022855, an anti–colony stimulating factor-1 receptor (CSF-1R) monoclonal antibody, in patients with advanced solid tumors refractory to standard therapy: phase 1 dose-escalation trial

3区 · 医学

Article

作者: Szpurka, Anna M ; Kauh, John Sae Wook ; Carlsen, Michelle ; Wesolowski, Robert ; Dowlati, Afshin ; Quinlan, Tonya ; Chapman, Sonya C ; Harvey, R Donald ; Yu, Danni ; Klempner, Samuel J ; Peterson, Daniel A ; Hamid, Omid ; Carvajal, Richard D

Background Tumor-associated macrophages (TAMs) promote tumor growth, metastasis, and therapeutic resistance via colony-stimulating factor-1 (CSF-1), acting through CSF-1 receptor (CSF-1R) signaling. This phase 1 study determined the safety, tolerability, pharmacokinetics-pharmacodynamics, immunogenicity, and efficacy of the anti-CSF-1R antibody LY3022855 in solid tumors. Methods Patients with advanced solid tumors refractory to standard therapy were enrolled and treated in 2 dosing cohorts: weight-based (part A) and non-weight-based (part B). Part A patients were assigned to intravenous (IV) dose-escalation cohorts: 2.5 mg/kg once per week (QW), 0.3 mg/kg QW, 0.6 mg/kg QW, 1.25 mg/kg once every 2 weeks (Q2W) and 1.25 mg/kg QW doses of LY3022855. Non-weight-based doses in part B were 100 mg and 150 mg IV QW. Results Fifty-two patients (mean age 58.6 ± 10.4 years) were treated with ≥1 dose of LY3022855 (range: 4-6). Five dose-limiting toxicities (left ventricular dysfunction, anemia, pancreatitis, rhabdomyolysis, and acute kidney injury) occurred in 4 patients. The non-weight-based 100 mg QW dose was established as the RP2D. The most common treatment-emergent adverse events were increase in liver function variables, fatigue, nausea, vomiting, diarrhea, anorexia, pyrexia, increased lipase, amylase, and lactate dehydrogenase. Clearance decreased with increasing dose and weight-based dosing had minimal effect on pharmacokinetics. Serum CSF-1, and IL-34 levels increased at higher doses and more frequent dosing, whereas TAMs and CD14dimCD16bright levels decreased. Three patients achieved stable disease. No responses were seen. Conclusions LY3022855 was well tolerated and showed dose-dependent pharmacokinetics-pharmacodynamics and limited clinical activity in a heterogenous solid tumor population. ClinicalTrials.gov ID NCT01346358 (Registration Date: May 3, 2011).

100 项与 LY-3022855 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
胰腺导管腺癌	临床1期	美国	Merck Sharp & Dohme Corp.	2018-09-27
胰腺导管腺癌	临床1期	美国	Eli Lilly & Co.	2018-09-27
局部晚期黑色素瘤	临床1期	美国	Eli Lilly & Co.	2017-06-06
非小细胞肺癌	临床1期	捷克	Eli Lilly & Co.	2016-06-16
非小细胞肺癌	临床1期	以色列	Eli Lilly & Co.	2016-06-16
非小细胞肺癌	临床1期	美国	Eli Lilly & Co.	2016-06-16
非小细胞肺癌	临床1期	比利时	Eli Lilly & Co.	2016-06-16
晚期恶性实体瘤	临床1期	美国	Eli Lilly & Co.	2011-06-15

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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


NCT02265536 (CTgov)	临床1期	肿瘤	34	LY3022855 (LY3022855 - 1.25 mg/kg Q2W Breast Cancer)	觸鹹製觸範淵獵鏇壓遞(膚遞築鏇壓餘襯築淵網) = 鏇壓膚積繭繭鑰襯鬱顧製積齋願鬱衊鬱窪衊醖 (壓壓鹹遞鹽憲築範鬱蓋, 廠醖艱醖製鏇簾壓鏇憲 ~ 範鑰壓廠憲鹽顧範網壓) 更多	-	2024-10-28
NCT02265536 (CTgov)	临床1期	肿瘤	34	LY3022855 (LY3022855 - 1.0 mg/kg WK1_2_4_5 Breast Cancer)	觸鹹製觸範淵獵鏇壓遞(膚遞築鏇壓餘襯築淵網) = 鑰醖鏇壓構獵觸鏇獵鹹製積齋願鬱衊鬱窪衊醖 (壓壓鹹遞鹽憲築範鬱蓋, 鹹簾艱獵鏇願夢製襯鑰 ~ 網構憲範鬱願膚醖餘鏇) 更多	-	2024-10-28
NCT03153410 (CTgov)	早期临床1期	胰腺腺癌 \| 胰腺导管腺癌	11	IMC-CS4+cyclophosphamide+GVAX Pancreas Vaccine (GVAX)+pembrolizumab+GVAX	鬱艱艱鏇鹽壓網網窪窪(醖遞繭蓋鹹餘遞醖鑰範) = 鏇壓膚繭夢餘廠醖膚觸壓獵獵艱選廠鏇鹽齋鹽 (窪窪夢夢範鏇構繭壓襯, 糧衊獵廠簾淵膚構網簾 ~ 繭製遞遞餘獵鏇襯餘壓) 更多	-	2024-10-15
NCT03101254 (CTgov)	临床1/2期	黑色素瘤 \| 局部晚期黑色素瘤	5	LY3022855+Cobimetinib+Vemurafenib	製鑰網醖製繭構夢鹽簾(蓋選艱觸廠網獵遞簾膚) = 醖築蓋鹽蓋鹽淵窪顧壓獵積築願壓鹽鏇鏇夢選 (鏇製獵製膚積鹽築艱範, 夢鏇餘製糧壓壓糧衊艱 ~ 鑰獵遞製製蓋鹹淵衊襯) 更多	-	2024-07-17
NCT02718911 (Pubmed \| Invest New Drugs) 人工标引	临床1期	实体瘤	72	durvalumab+tremelimumab+LY3022855	(淵膚夢淵鏇願遞醖襯夢) = maximum tolerated dose was not reached 襯壓淵蓋餘觸鹹築網鏇 (選鬱願夢網襯醖齋觸壓 ) 更多	积极	2021-10-01
NCT02718911 (Pubmed \| Invest New Drugs) 人工标引	临床1期	实体瘤	72	durvalumab+LY-3022855		积极	2021-10-01
NCT01346358 (Pubmed \| Invest New Drugs) 人工标引	临床1期	实体瘤	52	LY3022855	(鬱製鏇餘顧範製廠獵簾) = The non-weight-based 100 mg QW dose was established as the RP2D. 齋遞衊蓋餘醖網鏇窪艱 (網獵鏇遞鏇齋壓糧鬱顧 ) 更多	不佳	2021-08-01
NCT01346358 (ASCO2017)	临床1期	HR阳性/HER2低表达实体瘤	35	LY3022855	(窪齋築願鏇齋鏇鬱鏇廠) = 憲糧築製製壓窪遞壓壓醖顧構顧築遞膚選鑰廠 (範範鹹顧齋壓範餘鏇憲 ) 更多	-	2017-05-30