A Randomized, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Monotherapy Ontuxizumab (MORAb-004) Plus Best Supportive Care in Patients with Chemorefractory Metastatic Colorectal Cancer
A Randomized, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Monotherapy Ontuxizumab (MORAb-004) Plus Best Supportive Care in Patients with Chemorefractory Metastatic Colorectal Cancer
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DOI：
10.1158/1078-0432.ccr-17-1558
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发表时间：
2018-01-15
影响因子：
11.5
通讯作者：
Diaz, Luis Alberto, Jr.
中科院分区：
文献类型：
--
作者：
Grothey, Axel;Strosberg, Jonathan R.;Diaz, Luis Alberto, Jr.
目的：本研究的目的是评估ontuxizumab （MORAb-004）的安全性和有效性，这是一种干扰肿瘤内皮标志物-1功能的单克隆抗体，用于化疗难治性转移性结直肠癌患者，并根据生物标志物确定反应性患者群体。实验设计：这是一项随机、双盲、安慰剂对照的II期研究。患者以2:1的比例随机分配，接受每周静脉注射昂妥珠单抗（8mg /kg）或安慰剂加最佳支持治疗，直到病情进展或出现不可接受的毒性。评估组织和血液生物标志物识别对昂妥珠单抗有反应的患者群体的能力。结果：共纳入126例患者。在无进展生存期（PFS）的主要终点上，昂妥珠单抗组和安慰剂组之间没有明显的差异，两组的中位PFS为8.1周（HR, 1.13； 95%可信区间，0.76-1.67;P = 0.53）。两组间总生存期（OS）和总有效率（ORR）无显著差异。昂妥珠单抗组（分别与安慰剂组相比）最常见的治疗不良事件（teae）是疲劳（53.7%对47.5%）、恶心（39.0%对35.0%）、食欲下降（34.1%对27.5%）和便秘（28.0%对32.5%）。与安慰剂组相比，昂妥珠单抗组最常见的3/4级TEAE是背痛（11.0%对0%）。没有单一的生物标志物明确识别患者对昂妥珠单抗的反应。结论：与安慰剂相比，单药治疗在PFS、OS或ORR的临床反应参数方面没有益处。Ontuxizumab耐受性良好。(c) 2017 aacr。
Purpose: The purpose of this study was to evaluate the safety and efficacy of ontuxizumab (MORAb-004), a monoclonal antibody that interferes with endosialin (tumor endothelial marker-1) function, in patients with chemorefractory metastatic colorectal cancer and to identify a responsive patient population based on biomarkers.Experimental Design: This was a randomized, double-blind, placebo-controlled, phase II study. Patients were randomly assigned in a 2: 1 ratio to receive weekly intravenous ontuxizumab (8 mg/kg) or placebo plus best supportive care until progression or unacceptable toxicity. Tissue and blood biomarkers were evaluated for their ability to identify a patient population that was responsive to ontuxizumab.Results: A total of 126 patients were enrolled. No significant difference between the ontuxizumab and placebo groups was evident for the primary endpoint of progression-free survival (PFS), with a median PFS of 8.1 weeks in each group (HR, 1.13; 95% confidence interval, 0.76-1.67; P = 0.53). There were no significant differences between groups for overall survival (OS) or overall response rate (ORR). The most common treatment-emergent adverse events (TEAEs) in the ontuxizumab group (vs. the placebo group, respectively) were fatigue (53.7% vs. 47.5%), nausea (39.0% vs. 35.0%), decreased appetite (34.1% vs. 27.5%), and constipation (28.0% vs. 32.5%). The most common grade 3/4 TEAE in the ontuxizumab group versus placebo was back pain (11.0% vs. 0%). No single biomarker clearly identified patients responsive to ontuxizumab.Conclusions: No benefit with ontuxizumab monotherapy compared with placebo for clinical response parameters of PFS, OS, or ORR was demonstrated. Ontuxizumab was well tolerated. (C) 2017 AACR.