Ipafricept(Ipafricept) - 药物靶点：Wnt蛋白_专利_临床

概要

基本信息

药物类型

融合蛋白

别名

Ipafricept (USAN/INN)

+ [2]

靶点

Wnt蛋白

作用机制

Wnt蛋白抑制剂

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [1]

在研适应症-

非在研适应症

肝细胞癌卵巢癌胰腺癌+ [2]

原研机构

Mereo BioPharma 5, Inc.

在研机构-

非在研机构

Mereo BioPharma 5, Inc.

Bayer AG

最高研发阶段终止临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

登录后查看时间轴

序列信息

Sequence Code 9645812

来源: *****

关联

4

项与 Ipafricept 相关的临床试验

NCT02069145 / Completed临床1期

A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Sorafenib in Patients With Hepatocellular Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with sorafenib. OMP-54F28 will be administered IV on Day 1 of each 21-day cycle. The planned dose levels of OMP-54F28 are 5 and 10 mg/kg. Depending on safety in this study, additional lower or intermediate dose levels may be evaluated.

开始日期2014-01-01

申办/合作机构

Mereo BioPharma 5, Inc.

NCT02092363 / Completed临床1期

A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Paclitaxel and Carboplatin in Patients With Recurrent Platinum-Sensitive Ovarian Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with paclitaxel and carboplatin. OMP-54F28 will be administered IV on Days 1 of each 21-day cycle. Paclitaxel (175 mg/m2) and carboplatin (AUC = 5 mg/mL • min) will be administered IV on Day 1 of each cycle. A total of 6 cycles of paclitaxel and carboplatin will be given. Additional cycles may be given as per institutional standard of care after discussion with the Medical Monitor. Treatment with OMP-54F28 will continue after completion of treatment with paclitaxel and carboplatin. The planned dose levels of OMP-54F28 are 5 and 10 mg/kg.

开始日期2014-01-01

申办/合作机构

Mereo BioPharma 5, Inc.

NCT02050178 / Completed临床1期

A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Nab-Paclitaxel and Gemcitabine in Patients With Previously Untreated Stage IV Pancreatic Cancer

This is an open-label Phase 1b dose-escalation study to assess the safety, tolerability, and PK of OMP-54F28 when combined with nab-paclitaxel and gemcitabine. OMP-54F28 will be administered IV on Days 1 and 15 of each 28-day cycle. Nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) will be administered IV on Days 1, 8, and 15 of each cycle. The planned dose levels of OMP-54F28 are 3.5 mg/kg and 7.0 mg/kg.

开始日期2013-11-01

申办/合作机构

Mereo BioPharma 5, Inc.

100 项与 Ipafricept 相关的临床结果

登录后查看更多信息

100 项与 Ipafricept 相关的转化医学

登录后查看更多信息

100 项与 Ipafricept 相关的专利（医药）

登录后查看更多信息

8

项与 Ipafricept 相关的文献（医药）

2020-10-15·Clinical Cancer Research1区 · 医学

Phase Ib Study of Wnt Inhibitor Ipafricept with Gemcitabine and nab-paclitaxel in Patients with Previously Untreated Stage IV Pancreatic Cancer

1区 · 医学

Article

作者: Kapoun, Ann M. ; Brachmann, Rainer K. ; O'Neil, Bert ; Stagg, Robert J. ; Denlinger, Crystal S. ; Dotan, Efrat ; Lenz, Heinz-Josef ; Shahda, Safi ; Uttamsingh, Shailaja ; Astsaturov, Igor ; Cardin, Dana B. ; Cohen, Steven J. ; Weekes, Colin ; Messersmith, Wells

AbstractPurpose:The recombinant fusion protein ipafricept blocks Wnt signaling, and in combination with gemcitabine and nab-paclitaxel caused tumor regression in xenografts. This phase Ib study evaluated the combination of ipafricept with nab-paclitaxel + gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma (mPDAC).Patients and Methods:Dose escalation started with standard dose nab-paclitaxel + gemcitabine and ipafricept (3.5 mg/kg days 1, 15). Because of fragility fractures seen with different anti-Wnt agents, following cohorts had ≥6 patients treated with ipafricept 3 to 5 mg/kg on day 1, and included bone marker monitoring and prophylactic bisphosphonates as indicated. On the basis of preclinical data, sequential dosing was evaluated in cohort 4 (ipafricept day 1 followed nab-paclitaxel + gemcitabine day 3). Objectives included safety, MTD, recommended phase II dose, pharmacokinetics, immunogenicity, pharmacodynamics, and efficacy.Results:A total of 26 patients were enrolled, five in cohort 1 and seven each in cohorts 2–4. ipafricept-related adverse events (AEs) of any grade included fatigue, nausea, vomiting, anorexia, and pyrexia. ipafricept-related AEs grade ≥3 included two events of aspartate aminotransferase elevation, and one each of nausea, rash, vomiting, and leucopenia. No dose-limiting toxicities or fragility fractures were observed. Nine patients (34.6%) had partial response, 12 (46.2%) stable disease as best response, with clinical benefit rate of 81%. Median progression-free survival was 5.9 m [95% confidence interval (CI), 3.4–18.4], median overall survival was 9.7 m (95% CI, 7.0–14). The study was terminated by the sponsor due to bone-related toxicity within this therapeutic program and concerns for commercial viability. One patient remains on therapy under compassionate use.Conclusions:Ipafricept can be administered with nab-paclitaxel + gemcitabine with reasonable tolerance. Wnt pathway remains a therapeutic target of interest in mPDAC.

2020-03-16·Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics2区 · 医学

Frizzled Receptors in Tumors, Focusing on Signaling, Roles, Modulation Mechanisms, and Targeted Therapies

2区 · 医学

Review

作者: Wang, Wei ; Zhao, Chenghai ; Sun, Yu

Wnt molecules play crucial roles in development and adult homeostasis through their receptors Frizzled proteins (Fzds). Fzds mediate canonical -catenin pathway and various noncanonical -catenin-independent pathways. Aberrant Fzd signaling is involved in many diseases including cancer. Wnt/-catenin is a well-established oncogenic pathway involved in almost every aspect of tumor development. However, Fzd-mediated noncanonical Wnt pathways function as both tumor promoters and tumor suppressors depending on cellular context. Fzd-targeted therapies have proven to be effective on cultured tumor cells, tumor cell xenografts, mouse tumor models, and patient-derived xenografts (PDX). Moreover, Fzd-targeted therapies synergize with chemotherapy in preclinical models. However, the occurrence of fragility fractures in patients treated with Fzd-targeted agents such as OMP-54F28 and OMP-18R5 limits the development of this combination. Along with new insights on signaling, roles, and modulation mechanisms of Fzds in human tumors, more Fzd-related therapeutic targets will be developed.

2019-08-01·Gynecologic Oncology2区 · 医学

A phase 1b dose escalation study of ipafricept (OMP 54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer

2区 · 医学

Article

作者: Burger, Robert A ; Morgan, Mark A ; Farooki, Azeez ; Moore, Kathleen N ; McMeekin, D Scott ; Gunderson, Camille C ; Brachmann, Rainer Karl ; Stagg, Robert ; Mantia-Smaldone, Gina ; Kapoun, Ann M ; Sabbatini, Paul ; O'Cearbhaill, Roisin E

OBJECTIVESThe WNT pathway is an important oncologic driver of epithelial ovarian cancer (EOC). The first-in-class recombinant fusion protein ipafricept (IPA) blocks Wnt signaling through binding of Wnt ligands. This phase Ib trial was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RPh2) for IPA in combination with taxane and platinum therapy (C/P).METHODSDose escalation started with a standard 3 + 3 design for IPA/C/P with q3w intravenous IPA on Day 1, in cycles 1 to 6 with C (AUC = 5 mg/ml·min) and P (175 mg/m²). For enhanced bone safety the trial was revised to 6-patient cohorts with a q3w regimen of IPA on Day 1 and C/P on Day 3 (IPA → C/P).RESULTS37 patients have been treated; 30 of whom were treated following protocol revision to q3w IPA(D1) → C/P(D3) (2 & 4 mg/kg). IPA-related TEAEs that occurred in ≥15% included: fatigue (40%); nausea (35%); diarrhea and decreased appetite (22%) each; dysgeusia (19%); and vomiting (16.2%). 22% reported ≥1 IPA related TEAE Grade ≥3 the most common of which was neutropenia at 16%. There were no DLTs; the MTD was not reached. The maximum administered dose based on bone safety was 6 mg/kg. The overall response rate (ORR) was 75.7%. Median PFS was 10.3 months (95% CI 8.5-14.2) and OS 33 months (95% CI 23.4-NR).CONCLUSIONSIPA is well tolerated in combination with sequential C/P. ORR, PFS and OS are comparable to historical data but bone toxicity at efficacy doses of this particular Wnt inhibitor limit further development in EOC.

100 项与 Ipafricept 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11758	-	-	DB15045

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
铂敏感性卵巢癌	临床1期	美国	Mereo BioPharma 5, Inc.	2014-01-01
实体瘤	临床1期	美国	Bayer AG	2012-06-01
肝细胞癌	临床1期	-	Bayer AG	-
肝细胞癌	临床1期	-	Bayer AG	-
卵巢癌	临床1期	-	Bayer AG	-
胰腺癌	临床1期	-	Bayer AG	-
胰腺癌	临床1期	-	Bayer AG	-

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


NCT02050178 (Pubmed \| Clin Cancer Res) 人工标引	临床1期	胰腺癌一线	26	Gemcitabine+nab-paclitaxel+Ipafricept	(繭膚遞鹽壓構構艱鹽鬱) = 鹹艱夢簾願壓獵窪願醖壓觸艱鬱壓遞夢遞憲餘 (顧衊鏇糧構遞製鬱鏇糧, 3.4 ~ 18.4) 更多	不佳	2020-10-15
NCT02092363 (Pubmed \| Obstet Gynecol Surv) 人工标引	临床1期	铂敏感性卵巢癌	37	paclitaxel+carboplatin+ipafricept	(選襯網構範繭遞構衊獵) = 廠構積衊壓餘簾襯壓願鹽衊顧積遞艱壓鹹膚鹹 (膚範鑰鏇鏇鏇糧餘鬱淵 ) 更多	积极	2019-08-01
NCT02050178 (ASCO_GI2019)	临床1期	胰腺癌	26	Ipafricept + Nab-P/G	(製淵窪鏇遞鹹願襯選齋) = included 2 events of AST elevation, and 1 each of nausea, maculopapular rash, vomiting and WBC decrease 築範艱憲蓋選艱簾顧醖 (壓願壓網鹹製窪夢顧廠 ) 更多	积极	2019-01-29
NCT01608867 (Pubmed) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	26	Ipafricept	(鹹壓醖齋憲繭醖獵鏇鬱) = 15 mg/kg；Q3W 範繭鬱願鏇淵製鹽鹹範 (窪構壓壓窪構願廠簾壓 ) 更多	积极	2017-12-15
Phase 1b clinical studies (AACR2014)	临床1期	肝细胞癌 \| 卵巢癌	-	OMP-54F28	製壓獵獵餘範網構鏇鏇(淵簾選繭築鹹製製餘觸) = induction 觸網鹽網壓鹹齋獵膚築 (觸衊構襯糧膚獵顧膚鏇 ) 更多	积极	2014-10-01
Phase 1b clinical studies (AACR2014)	临床1期	肝细胞癌 \| 卵巢癌	-	OMP-54F28 + Sorafenib		积极	2014-10-01
NCT01608867 (ASCO2014)	临床1期	HR阳性/HER2低表达实体瘤	25	OMP-54F28	(膚夢鏇廠獵餘廠觸醖壓) = 獵顧鬱構觸齋憲製膚壓構獵壓繭糧鑰觸積壓廠 (鹹顧獵餘顧簾鹹鑰窪獵 ) 更多	-	2014-05-20