BIG BANG study (EPOC1703): multicentre, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy with binimetinib, encorafenib and cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer
BIG BANG study (EPOC1703): multicentre, proof-of-concept, phase II study evaluating the efficacy and safety of combination therapy with binimetinib, encorafenib and cetuximab in patients with BRAF non-V600E mutated metastatic colorectal cancer
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DOI：
10.1136/esmoopen-2019-000624
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发表时间：
2020-01-01
期刊：
影响因子：
7.3
通讯作者：
Yoshino, Takayuki
中科院分区：
文献类型：
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作者：
Kotani, Daisuke;Bando, Hideaki;Yoshino, Takayuki
虽然BRAF V600 E突变发生在5%-15%的转移性结直肠癌（mCRC）中，但最近报道BRAF非V600 E突变的范围为1.6%-5.1%。我们之前曾报道过，BRAF非V600 E突变可能对疗效结果产生负面影响，BRAF V600 E突变也可能对预治疗的mCRC患者的抗表皮生长因子受体（EGFR）抗体治疗产生负面影响。最近，同时抑制丝裂原活化蛋白激酶激酶（MEK）、BRAF和EGFR在BRAF V600 E突变患者和BRAF非V600 E突变患者中显示出相关的抗肿瘤活性，但仅在临床前模型中。（研究是一项多中心、II期研究，旨在评估疗效，binimetinib+encorafenib+西妥昔单抗联合治疗BRAF非V600 E突变型mCRC患者的安全性和概念验证，通过肿瘤组织（肿瘤组织组）或血液样本（液体活检组）鉴定。关键合格性标准包括东部肿瘤协作组的
Background While the BRAF V600E mutation occurs in 5%-15% of metastatic colorectal cancer (mCRC), BRAF non-V600E mutations were recently reported to range from 1.6% to 5.1%. We have previously reported that BRAF non-V600E mutations could have a negative impact on efficacy outcomes as well as BRAF V600E mutation for antiepidermal growth factor receptor (EGFR) antibody treatment for pretreated patients with mCRC. Recently, simultaneous inhibitions of mitogen-activated protein kinase kinase (MEK), BRAF and EGFR exhibited relevant antitumour activities in patients with BRAF V600E mutant and also in BRAF non-V600E mutant but only in the preclinical model.Trial design The BIG BANG (study is a multicentre, phase II study to assess the efficacy, safety and proof of concept of the combinations of binimetinib+encorafenib+cetuximab in patients with BRAF non-V600E mutated mCRC, identified by either tumour tissue (tumour tissue group) or blood samples (liquid biopsy group). Key eligibility criteria include Eastern Cooperative Oncology Group Performance Status of