Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Microsatellite Stable Colorectal Cancer

IF 3.3 3区 医学 Q2 ONCOLOGY
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引用次数: 0

Abstract

Background

Pembrolizumab, a monoclonal antibody against PD-1, has shown limited efficacy in patients with microsatellite stable or mismatch repair proficient (MSS/pMMR) metastatic colorectal cancer (CRC). We evaluated vicriviroc (small-molecule C-C motif chemokine ligand 5 antagonist) plus pembrolizumab in patients with advanced or metastatic MSS/pMMR CRC.

Patients and methods

This open-label, phase 2 trial (NCT03631407) enrolled adults with histologically confirmed, locally advanced, unresectable or metastatic CRC that was MSS per local assessment. All patients had received previous treatment with standard therapies. Patients were randomized 1:1 to vicriviroc 150 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks or vicriviroc 250 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks for up to 35 cycles (2 years). Primary endpoints were the objective response rate (ORR) as assessed by the investigator per RECIST v1.1, dose-limiting toxicities (DLTs), adverse events (AEs), and discontinuations due to AEs.

Results

Forty patients were enrolled and treated. ORR was 5% (95% CI, 0.1%-24.9%) in both treatment groups. There were no complete responses; 1 patient in each treatment group experienced a partial response. No patient in the vicriviroc 150 mg plus pembrolizumab group experienced a DLT. Two patients in the vicriviroc 250 mg plus pembrolizumab group experienced DLTs (1 grade 4 encephalopathy and 1 grade 4 pneumonitis).

Conclusion

The combination of vicriviroc at doses of 150 or 250 mg plus pembrolizumab 200 mg showed limited antitumor activity in patients with advanced or metastatic MSS/pMMR CRC. Toxicity with the combination was manageable.

Vicriviroc(MK-7690)与 Pembrolizumab 联合治疗晚期或转移性微卫星稳定型结直肠癌患者的安全性和有效性
背景抗 PD-1 的单克隆抗体 Pembrolizumab 对微卫星稳定或错配修复熟练(MSS/pMMR)转移性结直肠癌(CRC)患者的疗效有限。我们评估了vicriviroc(小分子C-C motif趋化因子配体5拮抗剂)联合pembrolizumab对晚期或转移性MSS/pMMR CRC患者的疗效。患者和方法这项开放标签的2期试验(NCT03631407)招募了经组织学确诊、局部晚期、不可切除或转移性CRC的成人患者,这些患者的局部评估结果为MSS。所有患者之前都接受过标准疗法的治疗。患者按照1:1的比例随机接受维克瑞罗150毫克口服,每天一次,加上彭博利珠单抗200毫克静脉注射,每3周一次;或维克瑞罗250毫克口服,每天一次,加上彭博利珠单抗200毫克静脉注射,每3周一次,最多35个周期(2年)。主要终点为研究者根据 RECIST v1.1 评估的客观反应率 (ORR)、剂量限制性毒性 (DLT)、不良事件 (AE) 以及因 AE 导致的停药。两个治疗组的 ORR 均为 5%(95% CI,0.1%-24.9%)。没有完全应答;每个治疗组都有一名患者出现部分应答。vicriviroc 150 mg+pembrolizumab 组没有患者出现 DLT。结论在晚期或转移性MSS/pMMR CRC患者中,剂量为150或250毫克的vicriviroc与200毫克pembrolizumab的联合用药显示出有限的抗肿瘤活性。联合用药的毒性是可控的。
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来源期刊
Clinical colorectal cancer
Clinical colorectal cancer 医学-肿瘤学
CiteScore
5.50
自引率
2.90%
发文量
64
审稿时长
27 days
期刊介绍: Clinical Colorectal Cancer is a peer-reviewed, quarterly journal that publishes original articles describing various aspects of clinical and translational research of gastrointestinal cancers. Clinical Colorectal Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of colorectal, pancreatic, liver, and other gastrointestinal cancers. The main emphasis is on recent scientific developments in all areas related to gastrointestinal cancers. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.
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