Phase II Study of Ganitumab, a Fully Human Anti-Type-1 Insulin-Like Growth Factor Receptor Antibody, in Patients With Metastatic Ewing Family Tumors or Desmoplastic Small Round Cell Tumors

被引：162

作者：

Tap, William D. ^{[1
]}

Demetri, George ^{[3
]}

Barnette, Phillip ^{[4
]}

Desai, Jayesh ^{[5
]}

Kavan, Petr ^{[6
]}

Tozer, Richard ^{[7
]}

Benedetto, Pasquale W. ^{[8
]}

Friberg, Gregory ^{[2
]}

Deng, Hongjie ^{[2
]}

McCaffery, Ian ^{[2
]}

Leitch, Ian ^{[2
]}

Badola, Sunita ^{[2
,9
]}

Chang, Sung

Zhu, Min ^{[2
]}

Tolcher, Anthony ^{[10
]}

机构：

[1] Univ Calif Los Angeles, Los Angeles Med Ctr, Los Angeles, CA USA

[2] Amgen Inc, Thousand Oaks, CA USA

[3] Dana Farber Harvard Canc Ctr, Boston, MA USA

[4] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA

[5] Royal Melbourne Hosp, Parkville, Vic 3050, Australia

[6] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada

[7] McMaster Univ, Juravinski Canc Ctr, Hamilton, ON, Canada

[8] Univ Miami Sylvester, Ctr Comprehens Canc, Miami, FL USA

[9] Amgen Inc, Cambridge, MA USA

[10] START, San Antonio, TX USA

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2012年 / 30卷 / 15期

关键词：

MONOCLONAL-ANTIBODY; SARCOMA FAMILY; GENE-EXPRESSION; FUSION PROTEIN; CANCER; RECURRENT; SURVIVAL; R1507; CT;

D O I：

10.1200/JCO.2011.37.2359

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Ganitumab is a fully human monoclonal antibody against type-1 insulin-like growth factor receptor (IGF1R). An open-label phase II study was conducted to evaluate the efficacy and safety of ganitumab monotherapy in patients with metastatic Ewing family tumors (EFT) or desmoplastic small round cell tumors (DSRCT). Patients and Methods Patients >= 16 years of age with relapsed or refractory EFT or DSRCT received 12 mg/kg of ganitumab every 2 weeks. Objective response rate (ORR) was the primary end point. Secondary end points included clinical benefit rate (CBR = complete + partial responses + stable disease [SD] >= 24 weeks) and safety and pharmacokinetic profiles of ganitumab. The relationship between tumor response and EWS gene translocation status and IGF-1 levels was evaluated. Results Thirty-eight patients (22 with EFT; 16 with DSRCT) received one or more doses of ganitumab. Twenty-four patients (63%) experienced ganitumab-related adverse events. Grade 3 related events included hyperglycemia (n = 2), thrombocytopenia (n = 5), neutropenia (n = 2), leukopenia (n = 1), and transient ischemic attack (n = 1). There were no grade 4 or 5 treatment-related events. Of 35 patients assessed for response, two had partial responses (ORR, 6%) and 17 (49%) had SD. Four patients had SD >= 24 weeks, contributing to a CBR of 17%. The pharmacokinetic profile of ganitumab was similar to that observed in the first-in-human trial. Elevation of IGF-1 levels was observed postdose. EWS-Fli1 translocations were analyzed by RNA sequencing and fluorescent in situ hybridization, and novel translocations were observed in EFT and DSCRT. No apparent relationship between tumor response and IGF-1 levels or EWS gene translocations was observed. Conclusion Ganitumab was well tolerated and demonstrated antitumor activity in patients with advanced recurrent EFT or DSRCT. J Clin Oncol 30:1849-1856. (c) 2012 by American Society of Clinical Oncology

引用

页码：1849 / 1856

页数：8

共 21 条

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