HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer.
HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician's choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer.
复制标题
DOI：
10.1186/s12885-016-2385-z
复制
发表时间：
2016-06-03
期刊：
影响因子：
3.8
通讯作者：
Yardley DA
中科院分区：
文献类型：
--
作者：
Miller K;Cortes J;Hurvitz SA;Krop IE;Tripathy D;Verma S;Riahi K;Reynolds JG;Wickham TJ;Molnar I;Yardley DA
人表皮生长因子受体2（HER 2）阳性乳腺癌是一种特别侵袭性的疾病，最终在标准治疗的转移患者中进展。蒽环类药物（如多柔比星）是治疗HER 2阳性乳腺癌的有效药物，特别是与曲妥珠单抗联合给药时-然而，多柔比星相关的心脏毒性限制了其使用。因此，许多患者从未接受过蒽环类药物治疗，即使在疾病进展时也是如此，尽管可能会获益。MM-302是一种新型HER 2靶向抗体-脂质体阿霉素偶联物，可特异性靶向HER 2 β过表达细胞。临床前和I期数据表明，MM-302作为单药治疗或与曲妥珠单抗联合治疗，可有效治疗既往接受过蒽环类药物治疗的HER 2阳性乳腺癌，而不会出现游离多柔比星制剂的心脏毒性。HERMIONE是一项比较MM-302+曲妥珠单抗与医生选择的化疗（吉西他滨、卡培他滨或长春瑞滨）+曲妥珠单抗的开放标签、多中心、随机（1：1）II期试验，计划入组250例蒽环类药物初治的局部晚期/转移性HER 2阳性乳腺癌患者。关键入选标准为：先前在任何情况下用曲妥珠单抗（有或没有帕妥珠单抗）治疗;帕妥珠单抗难治性或不耐受性（帕妥珠单抗难治性定义为在局部晚期或转移性情况下的进展，或在完成含帕妥珠单抗的新辅助和/或辅助治疗期间或12个月内的疾病复发）;和ado-曲妥珠单抗emtansine用于局部晚期或转移性疾病的疾病进展或不耐受。该试验目前正在美国、加拿大和西欧的研究中心进行。治疗将以21天为一个周期进行，并将持续至疾病进展或出现不可接受的毒性。主要终点是独立评估的无进展生存期（PFS）。将每6周评估一次肿瘤缓解，并根据RECIST v1.1进行定义。次要终点包括MM-302+曲妥珠单抗的经药物评估的PFS、总生存期（OS）、6个月和1年时的OS率、客观缓解率、安全性和耐受性、生活质量以及药代动力学特征。HERMIONE研究将评价MM-302+曲妥珠单抗在难治性HER 2阳性晚期/转移性乳腺癌患者中的疗效和安全性，这些患者无标准治疗，且无已证实的生存优势。Clinicaltrials.gov标识符：NCT 02213744。登记日期：2014年8月6日。本文的在线版本（doi：10.1186/s12885-016-2385-z）包含补充材料，可供授权用户使用。
Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab – however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody–liposomal doxorubicin conjugate that specifically targets HER2overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations. HERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab. The HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage. Clinicaltrials.gov identifier: NCT02213744. Registration date: 06AUG2014. The online version of this article (doi:10.1186/s12885-016-2385-z) contains supplementary material, which is available to authorized users.