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.

中文翻译：

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zilovertamab 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

Zilovertamab 是一种针对 ROR1 的人源化单克隆抗体，ROR1 是多种实体瘤（包括乳腺癌）的恶性细胞表达的癌胚抗原。先前的 1 期研究表明，zilovertamab 具有良好的耐受性并能有效抑制 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。符合条件的患者患有局部晚期、不可切除或转移性 HER2− 乳腺癌，东部合作组体能状态为 0-2，并且在晚期情况下既往未接受紫杉烷治疗。研究治疗包括在第 1 个周期的第 1 天和第 15 天以及每个 28 天周期的第 1 天静脉注射 600 mg 齐洛维他单抗 (IV)，同时每周静脉注射 80 mg/m2 紫杉醇。研究患者之前平均接受过 4 种局部晚期、不可切除或转移性疾病治疗（内分泌治疗 + 化疗）。没有患者因齐洛维他单抗的毒性而停止治疗。不良事件与紫杉醇已知的安全性一致。在 16 名患者中，6 名 (38%) 获得部分缓解，6/16 (38%) 患者疾病稳定作为最佳肿瘤缓解。齐洛维他单抗和紫杉醇的组合对于经过大量预处理的晚期乳腺癌患者来说是安全的且耐受性良好。有必要进一步评估齐洛维他单抗在乳腺癌患者中的 ROR1 靶向作用。试用注册：NCT02776917。于 2016 年 5 月 17 日在 ClinicalTrials.gov 上注册。