齐洛韦坦单抗联合紫杉醇治疗局部晚期/不可切除或转移性 Her2 阴性乳腺癌的 1b 期研究

IF 6.1 1区 医学 Q1 ONCOLOGY Breast Cancer Research Pub Date : 2024-02-26 DOI:10.1186/s13058-024-01782-0
Rebecca A. Shatsky, Hemali Batra-Sharma, Teresa Helsten, Richard B. Schwab, Emily I. Pittman, Minya Pu, Elizabeth Weihe, Emanuela M. Ghia, Laura Z. Rassenti, Alfredo Molinolo, Betty Cabrera, James B. Breitmeyer, George F. Widhopf, Karen Messer, Catriona Jamieson, Thomas J. Kipps, Barbara A. Parker
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引用次数: 0

摘要

Zilovertamab是一种靶向ROR1的人源化单克隆抗体,ROR1是包括乳腺癌在内的多种实体瘤恶性细胞表达的一种肿瘤胚胎抗原。之前的一项1期研究表明,zilovertamab耐受性良好,能有效抑制ROR1信号传导,从而激活ERK1/2、NF-κB和NRF2靶基因。这项1b期研究评估了zilovertamab联合紫杉醇治疗晚期乳腺癌患者的安全性和耐受性。符合条件的患者均为局部晚期、无法切除或转移性 HER2-乳腺癌,东方合作组表现状态为 0-2,且既往未接受过晚期紫杉类药物治疗。研究治疗包括在第1周期的第1天和第15天静脉注射600毫克齐洛韦他单抗,然后在每个28天周期的第1天静脉注射紫杉醇,每周静脉注射80毫克/平方米。研究患者此前曾接受过中位数为4次的局部晚期、不可切除或转移性疾病治疗(内分泌治疗+化疗)。没有患者因齐洛韦坦单抗引起的毒性而中断治疗。不良反应与已知的紫杉醇安全性相符。在16名患者中,6名(38%)患者有部分反应,6/16(38%)患者的最佳肿瘤反应是病情稳定。在接受过大量预处理的晚期乳腺癌患者中,zilovertamab和紫杉醇的联合用药安全且耐受性良好。有必要进一步评估使用齐洛韦坦单抗对乳腺癌患者进行ROR1靶向治疗的效果。试验注册:NCT02776917。2016年5月17日在ClinicalTrials.gov上注册。
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A phase 1b study of zilovertamab in combination with paclitaxel for locally advanced/unresectable or metastatic Her2-negative breast cancer
Zilovertamab is a humanized monoclonal antibody targeting ROR1, an onco-embryonic antigen expressed by malignant cells of a variety of solid tumors, including breast cancer. A prior phase 1 study showed that zilovertamab was well tolerated and effective in inhibiting ROR1-signaling, which leads to activation of ERK1/2, NF-κB, and NRF2 target genes. This phase 1b study evaluated the safety and tolerability of zilovertamab with paclitaxel in patients with advanced breast cancer. Eligible patients had locally advanced, unresectable, or metastatic HER2− breast cancer with Eastern Cooperative Group performance status of 0–2 and without prior taxane therapy in the advanced setting. Study treatment included 600 mg of zilovertamab administered intravenously (IV) on Days 1 and 15 of Cycle 1 and then Day 1 of each 28-day cycle along with paclitaxel weekly at 80 mg/m2 IV. Study patients had received a median of 4 prior therapies (endocrine therapy + chemotherapy) for locally advanced, unresectable, or metastatic disease. No patient discontinued therapy due to toxicity ascribed to zilovertamab. Adverse events were consistent with the known safety profile of paclitaxel. Of 16 patients, 6 (38%) had a partial response, and 6/16 (38%) patients had stable disease as best tumor response. The combination of zilovertamab and paclitaxel was safe and well tolerated in heavily pre-treated advanced breast cancer patients. Further evaluation of ROR1 targeting in breast cancer patients with zilovertamab is warranted. Trial Registration: NCT02776917. Registered on ClinicalTrials.gov on 05/17/2016.
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来源期刊
Breast Cancer Research
Breast Cancer Research 医学-肿瘤学
自引率
0.00%
发文量
76
期刊介绍: Breast Cancer Research is an international, peer-reviewed online journal, publishing original research, reviews, editorials and reports. Open access research articles of exceptional interest are published in all areas of biology and medicine relevant to breast cancer, including normal mammary gland biology, with special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal publishes preclinical, translational and clinical studies with a biological basis, including Phase I and Phase II trials.
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